Article

ISSN 0006-2979, Biochemistry (Moscow), 2024, Vol. 89, No. 2, pp. 322-340 © Pleiades Publishing, Ltd., 2024.

322

Evolution of Longevity in Tetrapods:

Safety Is More Important than Metabolism Level

Gregory A. Shilovsky

1,2,3,a

*, Tatyana S. Putyatina

, and Alexander V. Markov

Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

Faculty of Biology, Lomonosov Moscow State University, 119234 Moscow, Russia

Institute for Information Transmission Problems (Kharkevich Institute),

Russian Academy of Sciences, 127051 Moscow, Russia

e-mail: gregory_sh@list.ru, grgerontol@gmail.com

Received November 26, 2023

Revised December 4, 2023

Accepted December 29, 2023

Abstract— Various environmental morphological and behavioral factors can determine the longevity of repre-

sentatives of various taxa. Long-lived species develop systems aimed at increasing organism stability, defense,

and, ultimately, lifespan. Long-lived species to a different extent manifest the factors favoring longevity (geron-

tological success), such as body size, slow metabolism, activity of body’s repair and antioxidant defense systems,

resistance to toxic substances and tumorigenesis, and presence of neotenic features. In continuation ofour studies

of mammals, we investigated the characteristics that distinguish long-lived ectotherms (crocodiles and turtles)

and compared them with those of other ectotherms (squamates and amphibians) and endotherms (birds and

mammals). We also discussed mathematical indicators used to assess the predisposition to longevity in differ-

ent species, including standard indicators (mortality rate, maximum lifespan, coefficient of variation of lifespan)

and their derivatives. Evolutionary patterns of aging are further explained by the protective phenotypes and life

history strategies. We assessed the relationship between the lifespan and various studied factors, such as body size

and temperature, encephalization, protection of occupied ecological niches, presence of protective structures (for

example, shells and osteoderms), and environmental temperature, and the influence of these factors on the vari-

ation of the lifespan as a statistical parameter. Our studies did not confirm the hypothesis on the metabolism level

and temperature as the most decisive factors of longevity. It was found that animals protected by shells (e.g., turtles

with their exceptional longevity) live longer than species that have poison or lack such protective adaptations.

Theimprovement of defense against external threats in long-lived ectotherms is consistent with the characteristics

of long-lived endotherms (for example, naked mole-rats that live in underground tunnels, or bats and birds, whose

ability to fly is one of the best defense mechanisms).

DOI: 10.1134/S0006297924020111

Keywords: evolution, longevity, aging, lifespan, reptiles, amphibians, phenoptosis, anti-aging programs, oxidative

stress, gerontological success

Abbreviations: CV, coefficient of variation; LS, life span;

ROS,reactive oxygen species.

* To whom correspondence should be addressed.

INTRODUCTION

Aging manifests both biologically, as body deteri-

oration and impairment of motor, physiological, and

cognitive characteristics, and demographically (math-

ematically), as an increase in mortality with age [1-3].

Patterns of aging have been described by numer-

ous evolutionary theories, e.g., the theories of age-relat-

ed attenuation of selection pressure [4] and antagonistic

pleiotropy [5]. Disposable soma theory [6] complements

these concepts by stating that deleterious somatic mu-

tations may accumulate if the selection pressure on

these mutations is less than to mutations harmful to

the germline.

The probability of death, however, is not always de-

termined only by the degree of organism deterioration,

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 323

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

which increases with age and includes accumulation

of damage and errors [7]. In some cases, such deteri-

oration happens very quickly, for example, after re-

production (in semelparous animals) or to prevent

the spread of infection in a population. Academician

V. P. Skulachev has pointed out this fact, when he sug-

gested the concept of acute and chronic phenoptosis [8].

The lifespan (LS) and severity of aging processes

highly vary in different species.

In most animal groups, evolution has been accom-

panied by the increase in the complexity of organiza-

tion and appearance of new types of cells and tissues,

as well as new behavioral responses. This implies that

each evolutionary round along the path of increasing

complexity will lead to the emergence of new types of

degenerative disorders and impairments that would

determine both the maximum LS and the structure of

mortality in general.

The number of cells in organisms also increases

with the increase in the organism complexity (and size).

Traits contributing to longevity (gerontological

success) in Metazoa. Multicellular animals (Kingdom

Metazoa) lack a single common LS trend, but rather

demonstrates various local trends in this parameter.

First, a large number of primitive Metazoa are char-

acterized by the lack of aging, or negligible senescence [9].

Jones et al. [10] classified the red Gorgonian cor-

al Paramuricea clavata as a non-aging species, as the

probability of death for this coral does not increase

with age, with its LS reaching hundreds of years [10].

The jellyfish Turritopsis dohrnii is potentially immortal

due to the ability to return from the medusa stage back

to a polyp, thereby looping its life cycle [11]. Thefresh-

water Hydra magnipapillata is considered as potential-

ly immortal species as its death in laboratory settings

is close to zero and does not increase with age [12],

although according to Comfort [1], in nature, this or-

ganism lives for no more than three years. At the same

time, LS

(age at which 95% of individuals die at a giv-

en level of mortality) of H. magnipapillata in a labora-

tory is more than 1400 years [10].

All the above long-lived species inhabit aquatic

habitats; however, the list of traits promoting longev-

ity has significantly expanded after the water-to-land

transition [13-15]. The more primitive a species, the

easier to maintain the longevity traits of the taxa pre-

ceding this species on the evolutionary tree. It was

suggested [10] that aging is slowed down by asexual

reproduction [16], modularity, absence of germ–soma

differentiation [14, 16], absence of predation pressure,

shelter security [17], ability for regeneration, and pres-

ence of a small number of cell types [12].

At the same time, the difference in the size of cells

of the same type in different species is much less than

the difference in the size of organisms. This implies

that the number of cells in large organisms is higher

and, since a tumor can theoretically develop from a

single transformed cell, resistance to oncogenesis is an

important aspect in the predisposition to longevity in

large animals (Peto’s paradox) [18, 19]. It is believed

that retention of ability for growth and regeneration,

as well as slow metabolism and low body temperature

(which contribute to slower generation of oxidizing

radicals), are among the basic mechanisms ensuring

slow aging in animals. These features are typical for

the all-time LS champions, such as the small bivalve

mollusk Arctica islandica (507 years) and large and

very slow Greenland shark Somniosus microcephalus

(392 years).

Previously, we published an article on the evolu-

tion of longevity in mammals [15]. In this work, we

studied the mechanism of LS formation as a species-

specific trait and evolution of longevity in cold-blood-

ed (ectothermic) Tetrapoda, as well as gerontological

success as a special type of biological success. Here, we

have focused on reptiles and amphibians vs. mammals.

We analyzed the traits contributing to longevity (geron-

tological success) and compared the efficiency of using

these traits (gerontological success efficiency) in dif-

ferent clades of amphibians and reptiles (the latter in-

clude many long-lived species, first of all, turtles). The

article also discusses mathematical indicators used to

assess the propensity for longevity in different species.

These include standard and basal mortality rates and

their dispersion (coefficient of variation, CV), as well

as their derivatives. We chose to analyze the species

from the ectothermic taxa (with low metabolic rate but

great variation in size), in particular, the mechanisms

providing safety of these species and features of eco-

logical niches occupied by these animals. The LS val-

ues of vertebrate species used in this work were taken

from the largest Anage database [20] unless stated oth-

erwise. The tree for the LS distribution was construct-

ed using the classification of vertebrates from the En-

sembl database [21] and the LS data from the Anage

database. In this work, the LS value was defined as the

maximum age known for a discussed species.

THE TRAITS OF GERONTOLOGICAL SUCCESS

AND LONGEVITY IN DIFFERENT TAXA

OF TETRAPODA

From the evolutionary point of view, the main

goal of living organisms is to maximize their fitness as

the extent of organism’s genetic contribution to sub-

sequent generations. Therefore, all other things being

equal, a long life is preferable to a short life. However,

in reality, fitness is affected by multiple factors.

Beside the LS, fitness is influenced by fecundity,

extent of offspring protection, sociality, reproduc-

tive effort at various ages, parental contribution, etc.

SHILOVSKY et al.324

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

Hence, in terms of evolution, LS values optimal in dif-

ferent situations can be different (either low or high).

Therefore, there is no single global trend toward an

increase in the LS in the evolution of living organisms,

as well as there is no global trend toward, for exam-

ple, an increase in fecundity or parental contribution

(although other things being equal, both high fecundi-

ty and high parental contribution increase fitness).

The pattern of distribution of species with high

and low LS values along the phylogenetic tree of ani-

mals is quite complex. Analysis of this distribution for

vertebrates might help to identify and understand the

main factors involved in the evolution of longevity.

As we have mentioned previously, high LS is un-

common in nature and, apparently, not the most im-

portant trait for adaptation. Or this trait is too “ex-

pensive” in terms of selection, if most of mutations

increasing longevity are at the same time detrimental

to other components of adaptation (e.g., fecundity or

parental care).

The relationship between the aging rate and LS

isfar from unambiguous.

While life is short at high aging rates, it can be ei-

ther long or short at low aging rates, as it depends on

the basal mortality rate, including predation pressure.

Generally recognized traits contributing to longevity

in vertebrates (traits determining their gerontological

success) are retention of ability for growth and regen-

eration in adulthood [22], slow metabolism (fish, am-

phibians, reptiles) [23], retention of juvenile features

in adult animals (neoteny) (amphibians) [24-26], and

tolerance to high metabolic rates (due to the acquired

ability to fly) (birds) [27].

A high capacity for transitory reparative regen-

eration after a damage/loss of some organ parts is re-

tained in echinoderms (close relatives of vertebrates)

[28, 29]. Later in the evolution of vertebrates, such re-

generative capacity has decreased along with the in-

crease in the level of organization. For example, the

c-Answer gene discovered at the Institute of Informa-

tion Transmission Problems encodes a protein respon-

sible for regeneration in amphibians. However, this

gene has not been retained in mammals, which has

promoted (due to a decrease in the Fgf8 activity) the

development of the forebrain, a distinctive feature of

higher vertebrates [30]. The metabolic rate and, accord-

ingly, the rate of free radical generation by the mito-

chondria in ectothermic vertebrates, including fish,

reptiles, and amphibians, are lower compared to those

in endothermic vertebrates (birds and mammals).

This might has contributed to the evolution of high

LS and delayed aging in some species, including emer-

gence of extremely long-lived species (some sharks)

[22] and species with negligible senescence (some

members of the Cyprinidae family) [31]. Reinke etal.

[32] found that 26 out of 30 known vertebrate species

that can survive up to 100 years are ectotherms. These

data suggest that the factor contributing most to the

longevity in ectothermic vertebrates may be such ge-

rontological success-related trait as slow metabolism.

The emergence of long-livers in favorable habitats

results from the adaptive changes that include emer-

gence of traits favorable for longevity at the molecular

and cellular levels (maintenance of genetic stability, etc.)

or at the entire organism level (e.g., neoteny) [33, 34].

HALLMARKS OF GERONTOLOGICAL SUCCESS

IN REPTILES AND AMPHIBIANS

Amphibians and reptiles have their own geronto-

logical success-related features. Negligible senescence

was observed in at least one species in each group of

the ectotherms (frogs, salamanders, lizards, crocodiles,

and turtles) [1, 32].

Aging and longevity in reptiles and amphibians.

Slowly aging wild turtles are the leaders among the

studied Tetrapoda with respect to the degree of associ-

ation between low metabolism and slow aging/long LS.

For example, the longest LS was found for the larg-

est representatives of tortoises (Testudinidae), such as

the Galapagos giant tortoise (reaching the length of 2 m

and weighing up to 500kg) and Aldabra giant tortoise

(Aldabrachelys gigantea, or Testudo gigantea). The lat-

ter is a little smaller, although it holds the record for

the LS among reptiles [32]. According to the Anage da-

tabase, the LS of the largest (up to 7 m in length and

weighing up to 2000 kg) representative of the Order

Crocodilia, the saltwater crocodile Crocodylus porosus,

is more than 100 years, although this information needs

verification (“…might be true”). The factors favoring

long LS in this crocodile include an extremely high

resistance to infections (and, as a result, acute phe-

noptosis), which is due, inter alia, to the specific fea-

tures of its microbiome [18], ability to rapidly switch

metabolism and undergo hibernation, when necessary,

well-developed osmoregulation, parental care (protec-

tion of eggs), and almost complete absence of natural

enemies [35]. In amphibians, a relatively long LS is

typical of tailed amphibians. The longevity champion

among these animals is the olm (Proteus anguinus),

whose (calculated) LS exceeds 100 years. Large sala-

manders have a longer LS compared to the small ones.

The maximum LS in tailless amphibians does not ex-

ceed 30-45 years (figure).

The record holders include the common toad Bufo

bufo (40 years) and very large (up to 1.4 kg with a body

length of more than 24 cm) African bullfrog Pyxicepha-

lus adspersus (45 years).

Below, we discuss the traits contributing to lon-

gevity (gerontological success) that are typical of long-

lived ectotherms (crocodiles and tortoises) and com-

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 325

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

The life span (LS) values for different taxa of Tetrapoda. Numerical intervals indicate the LS range (in years) within a given

taxon. In case the Anage database contains only one species of the indicated taxon, the LS for this species is shown; *calculated

value.

pare them with the traits of other representatives of

ectotherms (scaled reptiles) and endotherms (birds and

mammals). Revealing the trends in the pace and shape

of aging in animals requires a well-developed mathe-

matical apparatus. Thus, the maximum LS values for

mammals (211 years for the bowhead whale) and am-

phibians (over 100 years for the olm) have been calcu-

lated. In addition to the approaches used for studying

physiological, morphological, and behavioral charac-

teristics, various mathematical methods have been

developed for analyzing the data on the LS (value

characterizing the fast–slow continuum), pace of ag-

ing (relative rate of age-related increase in mortality),

and association between the LS and various factors,

such as body size and temperature, encephalization,

protection of occupied ecological niches, presence of

protective structures (e.g., carapace and osteoderms),

habitat temperature, etc., as well as the effect of these

factors on the distribution of LS as a statistical value.

Thermoregulation. Another important factor in-

fluencing longevity is temperature [36]. On one hand,

active thermoregulation promotes adaptation by al-

lowing colonization of colder habitats and increasing

mobility [37], while many ectothermic animals (e.g.,

amphibians and reptiles) are active only at certain am-

bient temperatures. On the other hand, endothermic

animals (birds and mammals) spend a large amount

of energy to maintain a relatively constant body tem-

perature at varying ambient temperatures. The evolu-

tion of endothermy is associated with changes in many

parameters, such as metabolic rate, resilience, and

aerobic capacity. High body temperature promotes an

increase in the production of reactive oxygen species

(ROS), which are important factors of aging [38-40].

Moreira et al. [36] have shown that the body tem-

perature of endothermic animals is not significantly

higher than that of ectotherms. At the same time, the

rates of changes in the body temperature vary consid-

erably in the evolution of terrestrial tetrapods. Moreira

et al. [36] have calculated the body temperatures for the

ancestors of major clades of tetrapods using a multi-

ple variance Brownian motion model. The estimated

body temperature for the ancestor of tetrapods was

28.0°C (95% confidence interval 23.7-32.4). Theestimat-

ed body temperatures of the ancestors of crocodil-

ians (θ = 30.1°C [27.3-32.9], lepidosaurs (Squamata and

Rhynchocephalia) (θ = 28.5°C [24.0-32.9]), and turtles

(θ = 27.5°C [23.6-31.3]) were similar to the body tem-

perature of the inferred ancestor of tetrapods. Thean-

cestors of mammals (θ = 32.3°C [28.8-35.6]) and birds

(θ = 39.4°C [37.5-41.4]) had higher body temperatures,

while the ancestors of amphibians (θ = 24.0°C [20.2-

27.9]) had evolved lower body temperatures.

Within-group variance of body temperature is

much lower in mammals and birds than in amphibi-

ans. Values for crocodiles, lepidosaurians, and turtles

are intermediate and close to the average value for

theentire tree.

SHILOVSKY et al.326

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

The authors found that body temperatures show

strong phylogenetic signal and conservatism, i.e., body

temperature usually reflects the evolutionary history

of a species. Closer species have more similar body

temperatures, while some lineages have retained sim-

ilar temperatures during surprisingly long periods of

time (hundreds of millions of years). The body tem-

peratures of tetrapods are often unrelated to the cli-

mate, but is significantly associated with the day-night

activity patterns. Phylogenetic analysis of variance

revealed no significant differences between the mean

body temperatures of nocturnal and diurnal tetrapods

in general, nor within turtles and amphibians; howev-

er, the differences between the body temperatures in

the clades of birds and lepidosaurs were significant,

and mammals approached significance. Importantly,

the differences between nocturnal and diurnal species

were significant across ectotherms and across endo-

therms. In ectothermic animals and, surprisingly, in

endotherms, the body temperatures are usually higher

in diurnal species than in nocturnal ones. Therefore,

the body temperatures are largely related to the phy-

logeny and diurnal/nocturnal activity patterns within

and among the groups of tetrapods, rather than to the

climate and the endotherm–ectotherm divide [36].

Physiological aging. In contrast to mammals,

turtles and crocodiles continue to grow throughout

the lifetime and are characterized by extremely slow

demographic senescence and physiological aging [41].

Itis believed that some species, such as turtles and tor-

toises, can manifest negligible senescence, without a

marked increase in the mortality rate [42] and wors-

ening of body physiological state with age [43]; scaled

reptiles take an intermediate position [44]. Some authors

assign crocodiles to the group of species with negli-

gible senescence that also includes tortoises [18, 41].

At the same time, scaled reptiles (Squamata) display

both physiological aging (accumulation of age-related

degenerative changes, such as increased collagen stiff-

ness, increased content of defective enzyme molecules,

slower metabolic rate, and impaired stress response),

and reproductive senescence (age-related decline in

reproductive capacity and fertility and increase in the

reproductive productivity per gram of female body

weight) [41, 45]. The data on the gradual senescence of

lizards (oriental garden lizard Calotes versicolor) and

snakes (grass snake Natrix natrix) confirm the concept

on the commonality of aging events in scaled reptiles

and vertebrates [41]. The aging events common for

amphibians and mammals include an increase in the

number of collagen crosslinks, accumulation of pigments

lipofuscin and melanin (hallmarks of aging), decrease

in the metabolic rate, and loss of immunocompetence.

An advantage of scaled reptiles compared to mammals

is a less pronounced age-related increase in mortality

[10] and reproductive senescence [41]. In contrast to

mammals, amphibians are characterized by polyphy-

odonty, as well as the maintenance of neurogenesis,

myogenesis, and oogenesis throughout adulthood [46].

A similar assumption (based on the idea of positive

relationship between the metabolic rate and accumu-

lation of damage) states that cold-blooded animals liv-

ing in a warm climate age faster than their relatives

inhabiting colder areas. Reinke etal. [32] verified this

hypothesis using the data on the average, maximum,

and minimum temperatures in the habitats occupied

by the studied populations. It was found that reptiles

indeed demonstrate a weak positive relationship be-

tween the environmental temperature and aging rate.

In amphibians, however, this relationship is the oppo-

site: frogs and salamanders living in cool climates age

on average faster than their counterparts inhabiting

warmer regions. At high temperatures, aging is fast-

er in reptiles and slower in amphibians. It was shown

that the age of sexual maturity, median age, and LS of

the Andrew’s toad (Bufo andrewsi) increased with the

decrease in the mean annual temperature, while the

age of sexual maturity increased with the decrease in

the temperature seasonality, implying that tempera-

ture is the most important factor of the habitat. At the

same time, the body size increased with the increase

in precipitation during the driest month and UV-B sea-

sonality, but did not depend on temperature, which is

against the Bergmann’s rule [47].

Age-related changes in the mortality rate (ac-

tuarial aging rate). An extensive comparative study

of turtles living in nature and at zoos and aquariums

revealed that ~75% of 52 investigated species demon-

strated slow or negligible aging. The body mass of tur-

tles positively correlated with the adult LS. For approx-

imately 80% turtle species, the aging rates were lower

than in modern humans [43]. It should be noted that

although turtles in particular and reptiles in general

have been considered as “icons” of longevity and resis-

tance to aging [23, 48], there are some studies refuting

this idea [49, 50]. However, this controversy does not

apply to large turtles with the unlimited growth, but

rather to several small members of the Emydidae fam-

ily (American freshwater turtles), such as the common

box turtle Terrapene carolina (138 years), European

pond turtle Emys orbicularis (120 years), Blanding’s

turtle (Emydoidea blandingii, 77 years), and painted tur-

tle Chrysemys picta (61 years), which are considered

to be non-aging despite their limited growth. Similar

to the freshwater turtle Chrysemys picta (Emydidae)

described by Warner etal. [49], a slow age-related in-

crease in the mortality was demonstrated for small

(shell size, 23-35 cm) terrestrial African tortoises,

such as the forest hinge-back tortoise Kinixys erosa

(LS 24.8 years), Home’s hinge-back tortoise Kinixys ho-

meana, and Bell’s hinge-back tortoise Kinixys belliana

nogueyi (LS 26.5 years) of the Testudinidae family, i.e.,

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 327

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

the family that includes the gopher tortoise, for which

Jones etal. [10] have shown negative aging. The rela-

tionship between the mortality rate and age in nature

was almost linear and reached 100% at 17 years [51].

In view of the above, it becomes even more important

to assess the mortality persistence (the period during

which mortality does not increase; a plateau in the sur-

vival curve) and the characteristics of LS distribution.

Jones et al. [10] analyzed the mortality of animals

and plants in the period from puberty to the age cor-

responding to 95% death of the original sexually ma-

ture cohort using as a criterion the presence/absence

of senescence (the ratio of mortality at the age corre-

sponding to 95% death of the cohort to the average

mortality for the entire period under study). Although

the gopher tortoise (Gopherus agassizii) was declared

the most non-aging animal, the freshwater crocodile

Crocodylus johnstoni ended up in the middle of the

list, while long-living humans (Japanese women) and

animals demonstrating a near-zero mortality for a long

period of time (Southern fulmar Fulmarus glacialoides)

were classified as the most aging species. Due to the

high background mortality at the early age, the LS

for the extremely long-lived Scots pine Pinus sylvestris

was 30 years. Regarding long-lived species with a less

marked age-related increase in mortality (e.g., fresh-

water crocodile C.johnstoni, long-wristed hermit crab

Pagurus longicarpus, Scots pine Pinus sylvestris), as

well as animals with the average LS that reach the bar-

rier of 5% survival before they demonstrate physiolog-

ical senescence, the method suggested by Jones et al.

allows to characterize only a small part of their life cycle,

but not to assess manifestations of aging at its late stag-

es. For example, the great tit Parus major was assigned

to non-aging species, although it simply has no time to

age because of a high external mortality caused by pre-

dation pressure (the impact of mortality due to internal

causes will be low here). Its population comes to an end

even before reaching 50% of the species-specific LS.

In terms of gerontological success, it should be

noted that although the great tit is a biologically suc-

cessful species, it has no traits contributing to longev-

ity that would distinguish it among other birds. Its LS

(15.4 years) is not something outstanding for birds ei-

ther. At the same time, humans and Southern fulmars,

despite being susceptible to senescence (their mortal-

ity rate increases starting at a certain age), have the

traits contributing to the gerontological success (see

the article by Skulachev et al. [33] for such traits in hu-

mans and naked mole-rats).

Similarly, Cayuela et al. [51] compared the age-de-

pendent dynamics of mortality in three species of

terrestrial tortoises of the Testudinidae family [forest

hinge- back tortoise K. erosa (LS 24.8 years), Home’s

hinge- back tortoise K. homeana, and Bell’s hinge-back

tortoise K. belliana noguey (LS 26.5 years)] and three

snake species [Gaboon viper Bitis gabonica, rhinoceros

viper Bitis nasicornis, and spotted night adder Causus

maculatus (LS 6.6 years)]. The relationship between the

mortality rate and age in Kinixys tortoises was posi-

tive and linear, suggesting a gradual slow increase in

mortality throughout the entire lifetime of these ani-

mals. On the contrary, in the Bitis and Causus snakes,

the relationship between the mortality rate and age

was dramatically negative, indicating a positive senes-

cence in tortoises and negative senescence in snakes

[51]. In other words, according to Gompertz, it would

be much more difficult to predict the percentage of in-

dividuals with the average LS, the number of individu-

als with 25% and 75% of the maximum species-specific

LS, as well as the number of long-livers (90%) and su-

per-long-livers (95%) for amphibians and reptiles (not

to mention long-lived cnidarians or, even so, woody

plants) than for humans. We have arrived to a conclu-

sion that the classification proposed by Jones etal. [10]

allows to divide animals and plants only approximate-

ly based on the degree of age-related increase in the

probability of death, while assessment of susceptibili-

ty to physiological senescence requires more complex

models and indicators [34, 52, 53].

Coefficient of variation of LS (CV

). We have

studied CV

(as a standard deviaton of values relative

to the mean, %), as well as the asymmetry and excess

coefficients, in various representatives of the Animalia

[52, 53] using the data of the Max Planck Institute for

Demographic Research [10]. In contrast to humans and

laboratory animals, the values obtained for the over-

whelming majority of studied species were heteroge-

neous due to a great influence of background mortality

in nature, as well as the non-monotonous total mortali-

ty, especially at the earliest age. According to our ana-

lysis [52, 53] of the data obtained by Jones et al. [10],

the CV

value for the entire cohort of the freshwater

crocodile (C.johnstoni) was 195%, i.e., the sample was

extremely heterogenous (table).

To smooth out the problem of abnormally high

mortality (for example, infant and child mortality), a

truncation of the age interval under consideration is

used, for example, ages only up to the death of 95% of

individuals, or only the age from reaching sexual ma-

turity until the death of 95% of individuals (LS

) can

be considered [10, 32].

As mentioned above, this parameter is not ideal

but yet more reliable for testing the models (verifying

the association between the effects of various environ-

mental factors and LS) than the maximum LS, which

strongly depends on the sample size. If an animal can

die with a 1-to-100 probability of at the age of 10 years

and with the same probability at the age of 90 years,

the senescence is negligible. When using truncated

data sets, the parameters of LS distribution in human

are calculated starting from the age of 10 years (when

SHILOVSKY et al.328

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

Comparison of parameters of LS distribution for reptiles and humans

Species Order LS

Number of years since birth

excluded from analysis

Reptiles

Viviparous lizard

(Lacerta vivipara)

Scaled reptiles

(Squamata)

0 69 2.41 5.3

1 56 0.84 –0.29

Desert tortoise

(G.agassizii)

Turtles

(Testudines)

1 160 5.59 44.9

1 135 4.42 26.51

11 117 1.89 3.3

Freshwater crocodile

(C.johnstoni)

Crocodiles

(Crocodilia)

0 195 3.46 12.44

1 92 1.08 0.38

2 60 0.79 –0.01

11 34 0.86 0.38

Humans (Homo sapiens)

Japanese women

in 2009

Apes

(Primates)

122

0 16 –2.23 8.28

10 16 –1.73 4.63

Swedish women

born in 1881

0 58 –0.6 –1.12

1 47 –0.85 –0.51

10 37 –0.91 –0.08

Ache people

0 101 0.54 –1.25

2 61 –0.1 –1.29

10 55 –0.17 –1.2

Note. Coefficients of asymmetry (A

), excess(E

), and variation(CV

) of LS in reptiles as compared to humans from different

countries (Japanese and Swedish women, and Ache people living in the wild). The values for the entire cohort are shown in bold.

The values within a species are grouped with respect to the number of years since birth excluded from analysis.

the increase in the age-related mortality starts) [54] or

from the age of 12-15 years (age of sexual maturity)

[10]. Thus, reducing the contribution of the age-inde-

pendent component resulted in the CV

decrease from

60% to 15-20% (table). Similar CV

values were found

in twins (i.e., when the difference in the effect of ge-

netic component was close to zero) [55].

To illustrate to what extent 100% CV

indicates

the scatter of LS values, let us consider the dispersion

of LS values in a cohort for which the LS is determined

by the coin toss: tails correspond to 0 years, heads –

to100 years. Therefore, in addition to the maximum LS,

there will be one more region, in which the values will

concentrate, and this region will be most distant from

the longest LS (the situation that maximizes theCV

The average LS in this case will be 50, the standard

deviation will also be 50, and their ratio (CV

) will be

1 (or 100%). Accordingly, in the case of even greater

variance, with a larger number of low LS values (pre-

dominance of external mortality, which prevents indi-

viduals from reaching their species LS of 100 years),

the CV

value can increase even more.

The heterogeneity of a cohort with the exclud-

ed first year of life (CV

 = 92%) decreases due to the

removal of infant mortality. When the first two years

of life are excluded from the analysis, CV

decreas-

es to 60%. Exclusion of the first 11 years of life (i.e.,

before the age of sexual maturity according to Jones

et al.) results in the CV

decrease to 34% (table), while

the asymmetry and excess do not change significantly.

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 329

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

Therefore, exclusion of the first two years of life is

enough to eliminate the effect of extremely high infant

mortality, while truncation at the age of sexual maturi-

ty decreases CV

more than threefold. In all the cases,

there is a significant right-side asymmetry, indicating

a high mortality rate at the early age that decreases

later in life.

The value of excess (kurtosis) for the entire co-

hort is unacceptably high; in other cases, the excess

is close to zero. The CV

value for the entire cohort

of the Lacerta vivipara lizard was 69% due to the high

mortality rate in the first year of life. Exclusion of in-

dividuals that had died during the first year decreased

to 56%, indicating that the heterogeneity of the

population was preserved. The sample of the desert

tortoise G. agassizii was most heterogeneous, as CV

for the entire cohort was 160% (an extremely high

value). It can be suggested that at such values, neither

, nor the mean characterize the course of aging of

a studied population. Apparently, despite the long LS

and resistance to aging, the effect of infant mortality

was too high. When individuals that had died in the

first year of life (infant mortality) were excluded, the

in this cohort was 98%. When the first 11 years

of life were excluded, CV

became 56%. Although CV

decreased after exclusion of 11 years (due to the re-

moval of infant mortality, as well as to the reduction in

the number of individuals), it still remained very high.

High mortality rate was observed at an early age only;

it became low later in life and did not increase with

age. Our calculations showed that in tortoises, it is

necessary to exclude the first 25 years of life for a co-

hort to reach a partial homogeneity with respecttoLS

(CV

 = 33%). Until that age, the LS of tortoises to a

great extent depends on the background mortality.

Probably, this can explain the debates on whether tor-

toises get old (whether the probability of their death

increases with age) that have flared up in recent years.

Maintenance of ability for growth and repro-

duction. A unique physiology of reptiles, indetermi-

nate growth, and fecundity increasing throughout the

entire lifetime of adult females have motivated a num-

ber of the studies aimed to elucidate how physiology

at the mechanistic level, life at the organismal level,

and natural selection at the evolutionary time scale

regulate LS in this diverse taxonomic group [56-60].

In terms of gerontological success, both rapid growth

(with an increase in the metabolic rate) and its quick

cessation upon reaching a species-specific size seem to

be unfavorable. From the longevity point of view, the

most efficient strategy would be retaining the ability

to grow slowly throughout the lifetime [18]. The ex-

amples of such strategy can be found across the entire

evolutionary tree, from hydras, corals, and sponges

to baleen whales. Modern Archosauria have retained

all of the above growth strategies [61]. In each taxon,

there are idioadaptations ensuring biological success of

its members and, accordingly, different LSs. Forexam-

ple, short LS of a large animal would make this animal

uncompetitive; therefore, the larger the animal, the

longer the LS (in a general case). On the other hand,

large size makes an animal more sensitive to abrupt

environmental changes (due to high requirements of

such organism for resources and its sensitivity to the

living conditions) [62, 63]. Giant species have become

extinct in almost all orders of vertebrates, although

their size made them virtually invulnerable (giant tor-

toises and crocodiles, giant sloths, deer, rhinos, etc.).

Large amphibian Rhinesuchus whaitsi that looked like

a crocodile because of its size and general appearance

(“rasp crocodile”) had not survived the Permian–Trias-

sic extinction 250 million years ago.

The rate of evolution in reptiles is usually low, but

sometimes they develop quickly in response to envi-

ronmental changes (e.g., their size increases with the

climate warming) [64]. Ancestral forms of Archosauria

were characterized by a more rapid growth and higher

metabolic rate compared to their descendants [65, 66].

The transition to slow growth took place upon the

emergence of early Crocodilomorpha in the Late Trias-

sic. The Archosauria clade contained rapidly growing

species of Pseudosuchia, which also had not survived

the mass extinction in the Late Triassic [61]. Croco-

diles, which have not changed their appearance or

ecological niche (tropical wetlands), are a characteris-

tic example of stabilizing selection [67]. Having found

the optimal state, crocodiles maintain it until the envi-

ronment forces them to adapt to new conditions [64].

Although many representatives of the order Croc-

odilia continue growing throughout the entire life-

time[41], it was reported that the growth of the Amer-

ican alligator (Alligator mississippiensis; Alligatoridae)

stops sometime after maturation. Tortoises demon-

strate two types of growth: there are non-aging species

of land tortoises (Testudinidae) that grow unlimitedly

throughout the lifetime [Aldabra giant tortoise T. gi-

gantea (=A. gigantea), desert tortoise G. agassizii] and

small tortoises, whose growth stops by the age of 30-40

years. The latter are primarily small representatives

of the Emydidae family (American freshwater turtles),

including the common box turtle T. carolina (LS, 138

years), European pond turtle E. orbicularis (120 years),

the Blanding’s turtle E. blandingii (77 years), and pained

turtle C. picta (61 years). However, some members of

this group this group (T. carolina and E. orbicularis)

demonstrate negligible senescence [1, 48, 68]. It was also

suggested that sea turtles have a determinate growth

[69]. However, even if the growth is determinate, its

continuation after reaching sexual maturity is normal

for reptiles and distinguishes them from mammals and

birds [70]. For example, the ratio between the body

length at the age of sexual maturity and maximum

SHILOVSKY et al.330

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

body length of an adult individual is 0.95 for the Asian

elephant (Elephas maximus), 0.9 for the fur seal (Arc-

tocephalus forsteri) and 0.97 for the polar bear (Ursus

maritimus) [71-73]. In snakes, tortoises, and lizards,

this ratio is on average 0.68, 0.70, and 0.74, respective-

ly [74, 75].

Safety provision. As we have already discussed

[15], the evolution of longevity is promoted by the de-

velopment and improvement of defense mechanisms

and mechanisms for colonization of protected ecolog-

ical niches. Amphibians have a number of adaptive

limitations, such as living in wet habitats, inability to

live in sea water because of the lack of pelvic kidneys,

primitive defense systems (mainly, venoms), relative-

ly small size (there are no amphibians weighing more

than 100 kg), the absence of egg amniotic membrane,

and the absence of well-developed active defense sys-

tems. In reptiles, such defense systems are shells in

tortoises and impenetrable skin in crocodiles (adapta-

tions that amphibians lack). Some examples of “more

active” defense adaptations in tetrapods are venoms

excreted by skin glands or special structures (e.g.,

fangs). Phylogenetic studies have shown that each

order has its own model of evolution with respect to

venomousness. In particular, the evolution of venom

production is much less dynamic than the evolution

of intake of toxins with food. Finally, in contrast to

amphibians, reptiles demonstrate a positive association

between a higher species diversity and evolution of

production and use of venoms [76]. If an animal is pro-

tected against predators, e.g., by a strong carapace or

inedibility/toxicity/venomousness, we can expect that,

all other things being equal, it will grow old slower than

its unprotected relatives. Reinke etal. [32] considered

two types of protective adaptations– physical (tortoise

shells, strong scales in crocodiles and some scaled rep-

tiles) and chemical (various venoms) – and showed

that the aging of species with protective adaptations is

indeed on average slower compared to the unprotect-

ed species. The mean value of the coefficient β

in the

Gompertz equation characterizing the rate of aging is

0.05 in physically protected species, 0.28 in chemical-

ly protected species, and 0.47 in unprotected species,

demonstrating that protected species are tenfold more

advantageous with respect to this parameter.

Encephalization (increase in the brain size rela-

tively to the body size), which positively correlates with

longevity in mammals, can negatively correlate with

longevity in other vertebrates due to the extreme en-

ergy consumption by the brain that might exceed the

benefit of cognitive advantages of a large, more devel-

oped brain. For example, in cartilaginous fishes (but

not in bony fishes), encephalization correlates neg-

atively with the species-specific LS [77]. Studying the

trade-off between changes in the brain size and lon-

gevity in 265 species has shown a negative correlation

between the brain size and LS in reptiles (similar to

cartilaginous fishes [77]), but not in amphibians [78].

Analysis of this correlation in 40 frog species (taking

into account the influence of their common phyloge-

netic origin and body size) has shown a positive cor-

relation between the brain size, age of sexual matura-

tion, and LS (despite the fact that tailless amphibians

generally do not have a high LS compared to other

amphibians) [79]. Moreover, frogs with longer LS have

more developed ventral regions of the brain, including

olfactory bulbs [79].

DISCUSSION

Combination of evolutionary success and lon-

gevity (evolutionary strategies). The evolutionary

success of a taxonomic group is determined by its bi-

ological progress. The criteria of biological progress

include an increase in the number of individuals, area

expansion, and progressive differentiation, i.e., an in-

crease in the number of systematic groups comprising

this taxon. A long-term presence of a particular group

in the history of life on Earth vs. rapid extinction is

also regarded as an evolutionary success. A high num-

ber of individuals in a population can be maintained

by a large number of offspring (born at one time or

over N generations) and a short LS (strategy 1) or by a

small number of offspring (born at one time or over N

generations) and a long LS (strategy 2). A combination

of high fecundity and long LS (strategy 3) is relative-

ly rare and usually associated with a high early mor-

tality (turtles, fish). Species with a short LS and small

number of offspring (strategy 4) are typically unable

to maintain a large population size and become ex-

tinct. In contrast to mammals, the longevity champions

among amphibians and reptiles discussed in this ar-

ticle, namely, turtles and crocodiles, follow strategy 3

(a combination of high fecundity and long LS). In our

opinion, such combination of elements of the r- and

K-strategies can be explained by a high offspring mor-

tality at the early growth stages. Thus, the number of

offspring remaining at the beginning of cohort’s life is

already small (which is characteristic of the K-strategy

organisms). The mechanisms and features of longevity

assurance in the course of evolution were discussed in

our previous article [15]. Briefly, they include (i) direct

selection for delayed aging. All other things being equal,

a long life is always better than a short one as it leaves

more time for reproduction and, hence, higher fitness

(genetic contribution to subsequent generations). This

makes us wonder why such apparently harmful trait

as aging is conserved in the evolution; (ii) indirect se-

lection for delayed aging, which leads to the develop-

ment of adaptations that increase the organism’s de-

fense against certain dangers. Such adaptations can,

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 331

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

as a side effect, result in the extension of life. For ex-

ample, high regeneration capacity protecting against

injuries can also occasionally slow down aging; (iii) di-

rect selection for accelerated aging (phenoptosis hy-

pothesis), when aging either accelerates the evolu-

tion of some useful traits or ensures inheritance of

resources and kin selection, as it has been shown for

Caenorhabditis elegans and some salmonids [15, 80, 81].

In reptiles, acute phenoptosis leading to rapid aging

and death (similar to the death of marsupial mice af-

ter mating and salmonid fish after spawning) has been

shown for the African skink Mabuya buettneri [41];

(iv) indirect selection for accelerated aging (antagonis-

tic pleiotropy hypothesis [5]), which is based on the

fact that many alleles increase adaptability at the ear-

ly age (e.g., early fecundity) at the cost of more rapid

decrease in the adaptability at the older age. Selection

favors such alleles because the number of individuals

that live to an older age is always less than the num-

ber of individuals who survive to an earlier age even

in the absence of aging. Hence, the overall damage to

the adaptability from the late-onset deleterious traits

is always less than the damage from the early-onset

ones (i.e., early-onset traits are more important to se-

lection than the late-onset traits). As external nonselec-

tive mortality increases, the early-onset traits become

more important for selection than the late-onset ones;

in other words, the evolution of longevity favors safe-

ty; (v) “drift threshold,” when the probability of surviv-

ing to a certain age decreases with age even in non-

aging organisms, because there is no zero mortality [4].

Therefore, later manifestation of a harmful effect of

an allele suggests weaker selection against it. Sooner

or later, there comes an age when the selection elimi-

nating mutations deleterious at that or later age can no

longer resist the drift, leading to the free accumulation

of such mutations. Medawar called it “selection shad-

ow” (implying an existence of the age that cannot be

reached by the “light” of purifying selection), while a

more common name is the “drift limit.” The higher the

external nonselective mortality rate, the earlier the

age of the drift threshold for deleterious mutations of

a fixed level of harmfulness. Therefore, the safety of

an organism contributes to the evolution of longevity.

Efficiency of gerontological success in reptiles

and amphibians. Below, we summarized the factors of

gerontological success, both critical and less significant

for the longevity in reptiles and amphibians. The first

of the tentative causes of longevity is cold-blooded-

ness; the second one is body size (generally, the larger

the size, the longer the LS). However, in reptiles and

amphibians, lower metabolic rate (compared to mam-

mals) and ectothermy do not necessarily result in high

LS (figure). Thus, there are long-livers among large

crocodiles and tortoises (in contrast to mammals,

long-livers are found among terrestrial species but not

among sea turtles). We also noted a trend toward an

increase in the LS for the largest species in mammali-

an taxa, which is due to the association between these

parameters in the evolution. In mammals, this is true

for the baleen and toothed whales, walruses and seals,

primates, odd-toed ungulates, and some other groups.

The exceptions are the taxa in which the size of an-

imals has not increased but rather decreased during

the evolution (bats) and animals that had diverged

early from a given branch of the evolutionary tree

(e.g., family Bathyergidae that diverged from other ro-

dents). The tuatara (Sphenodon punctatus) is also char-

acterized by a long LS (90 years), but, unfortunately, it

is the only representative of Rhynchocephalia. Scaled

reptiles (Squamata) do not typically include long-

lived species [82]. Nevertheless, the studies of aging in

snakes have confirmed the hypothesis that links lon-

ger LS to the mechanisms of free radical generation

and DNA repair [56].

Phylogenetic analysis of variance (ANOVA) of body

temperature at the clade level showed a significant dif-

ference between the ectothermic and endothermic an-

imals. The difference became even more pronounced

for the amniote clades solely, when amphibians were

excluded from analysis. Endothermic animals have

lower rates of evolutionary changes in body tempera-

ture than ectotherms. Amphibians show strong differ-

ences in this parameter between each other compared

to other tetrapods. They have lower average body tem-

peratures and higher rates of evolutionary changes in

the body temperature. Therefore, the greatest differ-

ences in the evolution of body temperature in tetra-

pods can be seen between amphibians and amniotes.

No correlation between the LS and body temperature

was found in reptiles and amphibians. The depen-

dence on external temperatures and a low metabolic

rate do not guarantee longevity in cold-blooded ani-

mals [32].

Similar to ectotherms, lower metabolic rate in

endotherms does not imply an increase in the spe-

cies-specific LS. For example, birds usually age more

slowly than mammals of a similar size, although their

body temperature tends to be higher. Previously [15],

we discussed the fact that mammals have almost en-

tirely opted for a greater mobility and lesser depen-

dence on low temperatures, while losing a potential

longevity as a trade-off. Mammals live shorter lives

than birds, reptiles, and amphibians of the same body

weight. As for the all-time record holders, only baleen

whales have an approximately 20% longer LS than gi-

ant tortoises, with a more than a 100-fold difference

in weight. Nevertheless, LS is unevenly distributed

across the evolutionary trees of mammals, amphib-

ians, and reptiles. As has already been mentioned,

such universal approach to the longevity assurance as

slowing down metabolism is untypical for mammals

SHILOVSKY et al.332

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

and observed in the groups that had separated early

from the common evolutionary tree, e.g., in the Bathy-

ergidae rodents (mole-rats). Representatives of the

Bathyergidae family live longer lives (especially con-

sidering their body weight) [83] compared to other

evolutionary successful but generally short-lived ro-

dents [84]. Austad [2] has established that marsupials

(which form a sister clade to placental mammals) are

characterized by a low metabolic rate compared to

placentals, but have no long-lived species, i.e., have not

achieved longevity in return (figure). A placental an-

imal with a comparable body weight will live longer

than a marsupial. Moreover, marsupials have lost the

evolutionary race on all continents except Australia

and, in part, South America (while only one species

lives in North America).

Since accumulation of molecular damage, includ-

ing that resulting from oxidative stress, is an import-

ant component of aging, it can be assumed that due

to a higher metabolic rate, accumulation of damage

in endothermic animals is more rapid than in ecto-

therms. In this case, warm-blooded animals should age

more rapidly than amphibians and reptiles. However,

our analysis of data in the present work does not sup-

port this assumption. After introduction of necessary

corrections for the body mass and evolutionary rela-

tionships, the rate of aging in cold-blooded animals

proved to be not significantly different from that in

warm-blooded animals. At the same time, the rate of

aging strongly varies between the species [32, 36].

Slower aging has been shown for amphibians and

reptiles protected by shells, osteoderms, or venom;

atthe same time, species with shells or osteoderms live

longer than species with venom or without any protec-

tive adaptations [32]. The data on warm-blooded ani-

mals do not always confirm the “metabolic hypothe-

sis” either. This hypothesis works well at the level of

intraspecific variability (more rapid aging of individ-

uals with a higher body temperature), but is not that

obvious when comparing different species. For exam-

ple, birds usually age slower than mammals of a sim-

ilar size, although their body temperature is general-

ly higher. There is no correlation between the LS and

body temperature in reptiles and amphibians. Neither

low metabolic rate, nor dependence on external tem-

perature guarantee longevity in ectotherms [32].

Evolutionary theories of aging and longevity.

The theory proposed by Medawar [4] is based on the

classical evolutionary theory of aging, which states that

the main cause of aging is an insufficiently strong effect

of purifying selection on the late-onset harmful muta-

tions. Even if an animal does not age, it is not immor-

tal and, sooner or later, it will die from some external

causes (be it unfavorable environmental temperature/

humidity, lack of food, or predation pressure). If the

probability of death is constant (does not increase

with age), then the probability of surviving until the

age X decreases exponentially as X increases. Ifa mu-

tation reduces organism’s viability at the age that few

individuals survive to, then this mutation cannot be

eliminated by selection. Therefore, harmful mutations

with the late-onset effects would accumulate in the

population over time, and that is what causes aging

[32, 85]. Hence, the overall aging rate determined by

the mutation accumulation/selection balance should

depend on the level of external, age-independent mor-

tality. For example, if predation pressure is so great

that the prey has almost no chance to live for more

than two or three years, selection will not efficiently

eliminate mutations that reduce the viability beyond

that age. As a result, the prey will evolve toward rapid

aging (and early reproduction). Conversely, if external

threats are minimal, selection will favor the evolution

of slow aging. The role of protective adaptations is as

follows: if there are any (e.g., hard shell or inedibili-

ty/venomousness, etc.), it should be expected that, all

other things being equal, members of a given species

will age more slowly than unprotected members of the

related taxa. Reinke etal. [32] distinguished two types

of protective adaptations: physical (tortoise shells,

bony scutes in crocodiles and some scaled reptiles)

and chemical (all kinds of venoms), and showed that

protected species age on average slower than the un-

protected ones. We should note that the slower aging

of birds compared to mammals is also well account-

ed for by the “hypothesis of protective adaptations.”

After all, beside an enhanced resistance to oxidative

stress at the cellular level, birds have one of the best

protective adaptations invented by nature– the ability

to fly. Moreover, birds are threatened only by preda-

tors belonging to the same taxon (birds), while terres-

trial predatory species are more numerous and more

diverse in their taxonomic composition. In addition,

predatory species in the bird clade have appeared rel-

atively late, so that the evolution had been occurring

for a long time in the absence of predatory birds (not

belonging to the Neoaves taxon) [86]. The same is true

for bats (no predatory bat species have emerge at all),

which live on average much longer than nonflying an-

imals of the same size. In mammals, including naked

mole-rats and humans, the role of protective adapta-

tions contributing to the evolution of slow aging and

long life might have been played by the developed so-

ciality and existence of protected shelters [33, 34, 87].

In addition to the idea of age-associated weak-

ening of selection pressure, the classic evolutionary

theory of aging includes the concept of a balance be-

tween early adaptability (i.e., reproductive efficiency at

the early age) and long-term maintenance of viability.

Other things being equal, what happens at the early

reproductive age is more important for selection than

what happens later, because it is yet unknown whether

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 333

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

anindividual will survive to a later age or not. There-

fore, if there is a mutation increasing early adaptabil-

ity at the cost of a comparable decrease in late adapt-

ability, selection will most likely favor it, even if many

individuals have a chance to live until manifestation

of the negative effects of this mutation [5]. Apparent-

ly, mutations enhancing reproductive efficiency at a

young age often do it at the cost of accelerated body

deterioration or have other negative late-onset effects

(antagonistic pleiotropy). Therefore, we can expect a

negative correlation between the components of early

adaptability (the rate of attaining sexual maturity, fe-

cundity) and longevity (high LS, slow aging). Depend-

ing on the conditions (e.g., predation pressure), some

species will choose faster life history strategies (“live

fast, die young”), while other species will follow the

maxim “make haste slowly”. The data on reptiles and

amphibians are in good agreement with this hypothe-

sis. Reptiles that reach sexual maturity at a later age

are characterized by slower aging and longer life than

those with early maturation. Amphibians demonstrate

a significant positive relationship between fecundity

(the number of eggs hatched per year) and aging rate.

Similar to reptiles, the rate of attaining sexual matu-

rity in amphibians shows a negative correlation with

the LS. These data can explain an exceptional lon-

gevity of tortoises, since they have both good defense

mechanisms and a slow lifestyle (although advanced

cognitive functions are not associated with longer LS).

Therefore, the most important factors influencing the

aging rate and LS in tetrapods are environmental tem-

perature, protective adaptations, and age of the repro-

duction and fecundity onset. An amazing longevity of

tortoises is apparently due to the fact that they have

shells protecting them from predators. It should be

also noted that the LS of large crocodiles seems to be

greatly underestimated and, in fact, is more than 100

years for the largest species (see above). As regards to

the brain development (encephalization), the cognitive

advantages of a larger brain (e.g., better perception of

sensory information, cognitive processing, and behav-

ioral flexibility) provide more efficient resistance to

the external mortality factors and, consequently, indi-

rectly contribute to slower aging that extends the LS

(cognitive buffer hypothesis) [77, 88]. However, accord-

ing to the disposable soma theory [6], significant ener-

gy costs associated with the maintenance of nervous

tissue would jeopardize the energy budget of organ-

isms with larger brains, as well as their investment in

the maintenance and repair of somatic cells, thereby

accelerating aging and reducing the LS. Among ecto-

thermic animals, the high metabolic costs of the ner-

vous tissue formation seem to exceed the cognitive

benefits of developing a larger brain. Therefore, nat-

ural selection favors optimization of energy expendi-

tures rather than benefits provided by advanced cog-

nitive functions. Other popular hypotheses suggesting

that endotherms should age faster than ectotherms

because of more active metabolism and that ecto-

therms living in warm climates should age faster than

those living in cooler regions have not been confirmed

either.

CONCLUSIONS

In vertebrates, long-lived species can appear

among (i) representatives of evolutionary successful

taxa and (ii) species that had diverged early from the

taxa of evolutionary successful r-strategists. Such taxa

are characterized by the emergence of traits that give

them an advantage (e.g., eusociality, ability to fly, posi-

tion at the top of the food chain, etc.) and can often be

found together (positive covariation).

Thus, it is assumed that a species-specific LS has

a close functional relationship with other anatomical

and physiological characteristics of the species, simi-

lar in nature to the allometric relationships between

body size or metabolic rate and body mass [89].

Different traits demonstrate a varying degree of

impact on the LS. Therefore, it is important to distin-

guish between the following two categories of aging/

longevity factors.

(1)  Physiological/biochemical/molecular factors

with a direct effect on the aging rate [the rate of ROS

generation, efficiency of ROS control, activity of partic-

ular biochemical pathways and repair enzymes, etc.].

Such factors directly cause acceleration or slowing of

aging; they are results of previous selection for longev-

ity, which could be more or less intense depending on

the factors from category2.

(2)  Evolutionary factors [sociality, safety, low

level of external nonselective (age-independent) mor-

tality; most likely, size also belongs here because large

size does not automatically make an animal long-lived

but only creates prerequisites for a stronger selection

for longevity]. These factors determine the intensity of

selection for longevity (or vice versa, for a short life),

which can be assessed using approaches developed to

analyze the dispersion of LS values as a measure of

disorder (LS inequality, Gini coefficient, Keyfitz entro-

py, etc.) [34].

Although there might be many traits promoting

longevity, but their effect will be negligible. The rela-

tive rate of increase in the LS per unit of increase in

any trait evolving in a given taxon (e.g., per unit of

weight gain) will indicate the efficiency of this trait in

terms of longevity (gerontological success). The same

can be said about the rate of evolution of genes re-

sponsible for these traits. The presence in a given

taxon of genes determining longevity (genes for DNA

repair, cancer resistance, antioxidant defense, etc.)

SHILOVSKY et al.334

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

is often associated with the appearance of isoforms of

gene products typical for the long-lived species of this

taxon. Tortoise shell or sociality of naked mole-rats do

not slow aging per se. However, these factors increase

a probability that the population will undergo more

intense selection for longevity. As a result, some traits

from category1 will change, leading to an increase or

decrease in longevity.

The traits that give an advantage to a particular

taxon (e.g., cephalization in primates) will develop in

such taxa more rapidly or to a greater extent com-

pared to other taxa. Gerontologically successful taxa

often include species successful even against the exist-

ing background (naked mole-rat among Bathyergidae

and humans among Hominidae). In addition, due to

the long-term stabilizing selection, gerontologically

successful species are often relict species, such as the

short-beaked echidna Tachyglossus aculeatus, platypus

Ornithorhynchus anatinus, tuatara Sphenodon puncta-

tus, crocodiles, including long-lived C. porosus, Croco-

dylus niloticus, and Osteolaemus tetraspis, olm P. an-

guinus, West Indian Ocean coelacanth Latimeria cha-

lumnae, etc. A more complex body structure and faster

metabolism can contribute to the occupation of new

ecological niches and displacement of other animal

groups from the old ones [90]. However, in terms of

gerontological success, this might create new poten-

tially vulnerable complex systems, whose probability

of failure increases with age (the process of biological

aging, “slow phenoptosis”). The latter will be coun-

teracted by the improvement of body defense sys-

tems (anti-aging programs, according to Skulachev

etal. [34]), which will be reflected in the evolutionary

changes in the respective genes. The rate of evolution

of genes responsible for the development of traits ad-

vantageous for a given taxon (large brain, sociality,

shell, enzymes of venom synthesis pathway, etc.) can

be compared with the rate of evolution of genes re-

sponsible for the anti-aging programs (first of all, DNA

repair and antioxidant systems) [60, 91-95]. In addi-

tion, the problem of reducing the damage from ROS

produced by the mitochondria (one of the most known

aging factors) in long-lived species is often solved one

way or another [34, 39, 40, 59, 96, 97]. The data on am-

phibians and reptiles make it possible to find differ-

ences in the patterns of LS evolution and aging rate in

ectothermic tetrapods compared to endotherms. These

parameters proved to be more diverse in amphibians

and reptiles vs. mammals and birds. Each order of am-

phibians and reptiles contains non-aging species with

almost no age-related increase in the probability of

death [among endotherms, species with similar ther-

moregulation (mesotherms) are naked mole-rat and

platypus]. Species with efficient physical or chemical

defenses (hard scales, bony carapace, venom glands)

tend to live longer and age more slowly than the un-

protected species. This fact supports the classical evo-

lutionary hypothesis stating that the age-independent

mortality favors the evolution of rapid aging and short

LS (strategy 1; see the “Combination of evolutionary

success and longevity (evolutionary strategies)” section

above). For example, Drosophila and nematode C. ele-

gans live short lives, but their aging is very evident.

Experiments performed by the Markov’s group [98]

showed that there may be a selection for both a de-

crease and increase in the LS (aging slows down). Also,

there might be situations when a short LS is associ-

ated not with fast aging but with high mortality rate,

which is sufficient, however, for some individuals to

live until maturity and to leave enough offspring for

the population to reproduce (e.g., great tit P. major in

the study by Jones etal. [10]). The hypothesis of evolu-

tionary trade-off between early reproduction and lon-

gevity has also been confirmed: species reaching sex-

ual maturity early and producing numerous offspring

each year live shorter lives and age faster.

Therefore, the species-specific LS established in

the course of evolution results from the balance be-

tween several differently directed evolutionary forces.

We are especially interested in the traits contributing

to the long species-specific LS of tetrapods (traits of

gerontological success) and the efficiency of their use.

As we have discussed previously [15], the success of

mammals as a taxon has been due to homeothermy,

encephalization, increase in size, and, most important-

ly, sociality; however, such trends are generally not

typical for tetrapods.

Long LS requires not only a gerontological suc-

cess (the presence of traits promoting longevity), but

also efficient use of these traits, i.e., how the species

respond to aging and implement the anti-aging pro-

grams. Skulachev etal. [34] formulated this principle

as the “multiplicity of aging [and anti-aging] path-

ways.” Before that, there had been two extreme views

prevalent in gerontological literature. The first one is

the normal damage accumulation theory stating that

aging and its rate (fast–slow aging continuum) depend

only on the rates of damage appearance and its repair

in the body. The other extreme view was represented

by the evolutionary theories, first of all, the antagonis-

tic pleiotropy theory (see above), implying that genes

responsible for the growth/development/reproduction

during the first part of life provide so many benefits

that they outweigh their negative effect in the second

part of life. In our opinion, these ideas do not contra-

dict each other and can be correct at the same time.

For example, if there is a mutation that increases ear-

ly fecundity in a given species at the cost of accelerat-

ed damage accumulation with age, then selection can

theoretically support this mutation because, for exam-

ple, early fecundity in this species appears to be more

important for general adaptability than accelerated

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 335

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

damage accumulation. This would be both a typical

example of antagonistic pleiotropy and an illustration

of the fact that aging depends on the rate of damage

accumulation and repair [89]. Both theories seem to be

compatible with each other. It is difficult to unambig-

uously identify such systems and signaling cascades,

perhaps, with the exception of those responsible for

the growth, proliferation, and regeneration.

In continuation of our work on mammals, here

we compared the traits that promote longevity in the

sister clades of amphibians and reptiles that include a

large number of long-lived species, especially tortoises.

The mathematical indicators used to assess a predis-

position to longevity in different species include both

standard indicators [mortality rate, basal mortality

rate, its variance (CV

)] and their derivatives. The pro-

tective phenotypes and life-history strategies provide

further explanation for the macroevolutionary pat-

terns of aging, while analysis of ectothermic tetrapods

in a comparative context expands our understanding

of the evolution of aging.

The evolution of longevity is associated with main

evolutionary trends, whose criterion is biological prog-

ress. Longevity per se is very rarely relevant for the

evolutionary success; therefore, there is not a single

high-ranking taxon whose success is caused by the

predisposition for longevity. Indeed, longer LS is rarely

advantageous both in the intergroup and intragroup

selection. While improving in the process of evolution

and ensuring their evolutionary success, taxa can gain

some traits contributing to longevity but lose some

other traits. The evolution of these processes can be

explained within the framework of the theory sug-

gested by Skulachev etal. [34, 81] on the diversity of

aging and anti-aging ontogenetic programs in animals

in general and in reptiles and amphibians in particu-

lar. Thus, the level of external mortality, which deter-

mines the selection pressure on the late-onset harmful

mutations, and the trade-off between a fast life and a

long life (the two factors predicted by the evolutionary

theory of aging) in all likelihood have a stronger im-

pact on the evolution of longevity in terrestrial verte-

brates than the intensity of metabolism. As regards en-

cephalization, the high metabolic costs of the nervous

tissue formation in ectothermic animals apparently

exceed the cognitive benefits of developing a larger

brain. This leads to the optimization of energy expen-

ditures in the course of natural selection rather than

to the development and improvement of cognitive

functions.

Other two popular hypotheses suggesting that

warm- blooded animals should age faster than cold-

blooded animals because of higher metabolic rates and

that cold-blooded animals living in the regions with a

warm climate should age faster than those living in

colder regions, have not been confirmed. This implies

that the high metabolic rate leading to the accelerated

accumulation of molecular damage is a less important

factor in the evolution of aging than selection for the

ability to repair this damage. The comment by Sacher

[89] that it is not the metabolic rate that matters, but

rather the quality of metabolism (i.e., how optimal it

is), is in agreement with the theory of gerontological

success proposed by us. Apparently, it has to be accept-

ed that metabolic rate is not a crucial factor in the evo-

lution of aging.

Molecular damage of any nature (generation of

ROS, loss of telomeres, cytokine production by aging

cells, or DNA damage) accumulate faster at a higher

metabolic rate. However, the evolutionary fate of a

species, i.e., the eventual rate of its aging, seems to be

determined not so much by the rate of damage accu-

mulation, but rather by the strength of selection for

the ability to repair this damage, which includes, in

addition to the DNA repair and antioxidant defense

systems [91, 60, 92, 93, 97, 99, 100], the control of mito-

chondrial ROS production [39, 96] and the presence of

extremely diverse (starting already from unicellular

organisms) cell death pathways eliminating senescent

and transformation-prone cells [34, 101, 102].

In this sense, evolution is stronger than biochemis-

try. For example, factors affecting the aging rate and LS

in tetrapods are temperature, the presence of protec-

tive adaptations, and the age of the reproduction and

fecundity onset. However, an exceptional longevity of

tortoises (in contrast to mammals) seems to be pri-

marily related not to the low metabolic rate, advanced

brain, or sociality, but to the presence of defensive

structures (shells) protecting them from predators.

However, here it is necessary to mention once

again the concept of gerontological success efficiency:

factors extremely favorable for the LS in some tetra-

pods will not necessarily be equally favorable in other

tetrapods. Thus, in armadillos (Mammalia, Cingulata)

protected with an armor of articulated osteoderms,

the longevity quotient (LS adjusted for the body

weight, one of the simplest indicators of gerontological

success efficiency) varies within a range of 1.12 to 1.5.

Only one species, the southern three-banded armadil-

lo Tolypeutes matacus, has a relatively high longevity

quotient (LQ) (2.46) that is approximately equal to the

longevity quotient of the chimpanzee Pan troglodytes

(2.70). Animals with the top longevity quotient val-

ues (calculated for mammals) include naked mole-rat

(3.68), humans (4.63), and several species of common

bats, with the highest longevity quotient found for

the Brandt’s bat Myotis brandtii (6.43). The improve-

ment, first and foremost, of the mechanisms provid-

ing safety is consistent with the defense pathways of

naked mole-rats (dwelling in burrows) and chiropter-

ans (ability to fly, which is also one of the best defense

adaptations).

SHILOVSKY et al.336

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

Acknowledgments. The authors are grateful

to S. V. Ogurtsov (Department of Vertebrate Zoology),

A. V. Seliverstov, and O. S. Luchkina for their valuable

advice while writing the article.

Contributions. G.A.S. developed the concept

ofthe work, T.S.P., A.V.M., and G.A.S. wrote and edited

the manuscript and prepared tables and figure.

Funding. This work was supported by ongoing in-

stitutional funding. No additional grants to carry out

or direct this particular research were obtained.

Ethics declarations. This work does not contain

any studies involving human and animal subjects.

The authors of this work declare that they have no

conflicts of interest.

REFERENCES

1. Comfort, A. (1979) The Biology of Senescence, Churchill

Livingstone, Edinburgh and London.

2. Austad, S. N. (1997) Why We Age, John Wiley and Sons,

New York.

3. Finch, C.E. (2009) Update on slow aging and negligible

senescence– a mini-review, Gerontology, 55, 307-313,

doi:10.1159/000215589.

4. Medawar, P. B. (1952) An Unsolved Problem of Biology,

H. C. Lewis& Co LTD, London.

5. Williams, G.C. (1957) Pleiotropy, natural selection and

the evolution of senescence, Evolution, 11, 398-411,

doi:10.1111/j.1558-5646.1957.tb02911.x.

6. Kirkwood, T.B.L. (1977) Evolution of ageing, Nature,

270, 301-304, doi:10.1038/270301a0.

7. Rando, T. A., and Chang, H. Y. (2012) Aging, rejuve-

nation, and epigenetic reprogramming: resetting

the aging clock, Cell, 148, 46-57, doi: 10.1016/j.cell.

2012.01.003.

8. Skulachev, M. V., and Skulachev, V. P. (2014) New

data on programmed aging – slow phenoptosis,

Biochemistry (Moscow), 79, 977-993, doi: 10.1134/

S0006297914100010.

9. Vaupel, J. W., Baudisch, A., Dölling, M., Roach, D. A.,

and Gampe, J. (2004) The case for negative senes-

cence, Theor. Popul. Biol., 65, 339-351, doi: 10.1016/

j.tpb.2003.12.003.

10. Jones, O. R., Scheuerlein, A., Salguero-Gómez, R., Ca-

marda, C. G., Schaible, R., Schaible, R., Casper, B. B.,

Dahlgren, J. P., Ehrlén, J., García, M. B., Menges, E.,

Quintana-Ascencio, P.F., Caswell,H., Baudisch,A., and

Vaupel, J.W. (2014) Diversity of ageing across the tree

of life, Nature, 505, 169-173, doi:10.1038/nature12789.

11. Pascual-Torner, M., Carrero, D., Pérez-Silva, J. G., Ál-

varez-Puente, D., Roiz-Valle, D., Bretones, G., Rodrí-

guez, D., Maeso, D., Mateo-González, E., Español, Y.,

Mariño,G., Acuña, J.L., Quesada,V., and López-Otín,C.

(2022) Comparative genomics of mortal and immor-

tal cnidarians unveils novel keys behind rejuvena-

tion, Proc. Natl. Acad. Sci. USA, 119, e2118763119,

doi:10.1073/pnas.2118763119.

12. Martínez, D.E. (1998) Mortality patterns suggest lack

of senescence in hydra, Exp. Gerontol., 33, 217-225,

doi:10.1016/s0531-5565(97)00113-7.

13. Bilinski,T., Bylak,A., and Zadrag-Tecza,R. (2016) Prin-

ciples of alternative gerontology, Aging (Albany NY),

8, 589-602, doi:10.18632/aging.100931.

14. Bilinski,T., Bylak,A., Kukuła,K., and Zadrag-Tecza,R.

(2021) Senescence as a trade-off between successful

land colonisation and longevity: critical review and

analysis of a hypothesis, PeerJ, 9, e12286, doi:10.7717/

peerj.12286.

15. Shilovsky, G. A., Putyatina, T. S., and Markov, A. V.

(2022) Evolution of longevity as a species-specific trait

in mammals, Biochemistry (Moscow), 87, 1579-1599,

doi:10.1134/S0006297922120148.

16. Martinez, D. E., and Levinton, J. S. (1992) Asexual

metazoans undergo senescence,

Proc. Natl. Acad. Sci.

USA, 89, 9920-9923, doi:10.1073/pnas.89.20.9920.

17. Healy, K., Ezard, T. H. G., Jones, O. R., Salguero-

Gómez, R., and Buckley, Y. M. (2019) Animal life his-

tory is shaped by the pace of life and the distribution

of age-specific mortality and reproduction, Nat. Ecol.

Evol., 3, 1217-1224, doi:10.1038/s41559-019-0938-7.

18. Hoekstra, L. A., Schwartz, T. S., Sparkman, A. M.,

Miller, D. A. W., and Bronikowski, A. M. (2020) The

untapped potential of reptile biodiversity for un-

derstanding how and why animals age, Funct. Ecol.,

34, 38-54, doi:10.1111/1365-2435.13450.

19. Dart,A. (2022) Peto’s paradox put to the test, Nat. Rev.

Cancer, 22, 129, doi:10.1038/s41568-022-00447-4.

20. De Magalhães, J. P., and Costa, J. (2009) A database

of vertebrate longevity records and their relation to

other life–history traits, J. Evol. Biol., 22, 1770-1774,

doi:10.1111/j.1420-9101.2009.01783.x.

21. Martin, F. J., Amode, M. R., Aneja, A., Austine-Orim-

oloye,O., Azov, A.G., Azov, A.G., Barnes,I., Becker,A.,

Bennett,R., Berry,A., Bhai,J., Bhurji, S.K., Bignell,A.,

Boddu, S., Branco Lins, P. R., Brooks, L., Ramaraju,

S.B., Charkhchi,M., Cockburn,A., Da Rin Fiorretto,L.,

Davidson, C., Dodiya, K., Donaldson, S., El Houdai-

gui,B., El Naboulsi,T., etal. (2023) Ensembl 2023, Nu-

cleic Acids Res., 51, 933-941, doi:10.1093/nar/gkac958.

22. Nielsen, J., Hedeholm, R.B., Heinemeier,J., Bushnell,

P.G., Christiansen, J. S., Olsen,J., Ramsey, C. B., Brill,

R. W., Simon, M., Steffensen, K. F., and Steffensen,

J.F. (2016) Eye lens radiocarbon reveals centuries of

longevity in the Greenland shark (Somniosus micro-

cephalus), Science, 353, 702-704, doi: 10.1126/science.

aaf1703.

23. Congdon, J.D., Nagle, R.D., Kinney, O.M., van Loben

Sels, R.C., Quinter,T., and Tinkle, D.W. (2003) Testing

hypotheses of aging in long-lived painted turtles (Chry-

semys picta), Exp. Gerontol., 38, 765772, doi: 10.1016/

s0531-5565(03)00106-2.

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 337

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

24. Voituron, Y., De Fraipont, M., Issartel, J., Guillau-

me,O., and Clobert,J. (2011) Extreme lifespan of the

human fish (Proteus anguinus): a challenge for age-

ing mechanisms, Biol. Lett., 7, 105107, doi: 10.1098/

rsbl.2010.0539.

25. Kostanjšek,R., Diderichsen,B., Recknagel,H., Gunde-

Cimerman,N., Gostinčar,C., Fan,G., Kordiš,D., Tron-

telj,P., Jiang,H., Bolund,L., and Luo,Y. (2022) Toward

the massive genome of Proteus anguinus-illuminating

longevity, regeneration, convergent evolution, and

metabolic disorders, Ann. N. Y. Acad. Sci., 1507, 5-11,

doi:10.1111/nyas.14686.

26. Voituron, Y., Guillaume, O., Dumet, A., Zahn, S., and

Criscuolo, F. (2023) Temperature-independent telo-

mere lengthening with age in the long-lived human

fish (Proteus anguinus), Proc. Biol. Sci., 290, 20230503,

doi:10.1098/rspb.2023.0503.

27. Delhaye, J., Salamin, N., Roulin, A., Criscuolo, F.,

Bize,P., and Christe,P. (2016) Interspecific correlation

between red blood cell mitochondrial ROS produc-

tion, cardiolipin content and longevity in birds, Age

(Dordr), 38, 433-443, doi:10.1007/s11357-016-9940-z.

28. Amir,Y., Insler,M., Giller,A., Gutman,D., and Atzmon,G.

(2020) Senescence and longevity of sea urchins, Genes

(Basel), 11, 573, doi:10.3390/genes11050573.

29. Medina-Feliciano, J.G., and García-Arrarás, J.E. (2021)

Regeneration in echinoderms: molecular advance-

ments, Front. Cell. Dev. Biol., 9, 768641, doi: 10.3389/

fcell.2021.768641.

30. Korotkova, D. D., Lyubetsky, V. A., Ivanova, A. S.,

Rubanov, L.I., Seliverstov, A. V., Zverkov, O.A., Mar-

tynova, N.Y., Nesterenko, A.M., Tereshina, M.B., Pe-

shkin, L., and Zaraisky, A. G. (2019) Bioinformatics

screening of genes specific for well-regenerating ver-

tebrates reveals c-answer, a regulator of brain devel-

opment and regeneration, Cell Rep., 29, 1027-1040.e6,

doi:10.1016/j.celrep.2019.09.038.

31. Kolora, S.R.R., Owens, G.L., Vazquez, J.M., Stubbs,A.,

Chatla, K., Jainese, C., Seeto, K., McCrea, M., Sand-

el, M. W., Vianna, J. A., Maslenikov, K., Bachtrog, D.,

Orr, J.W., Love,M., and Sudmant, P.H. (2021) Origins

and evolution of extreme life span in Pacific Ocean

rockfishes, Science, 374, 842-847, doi:10.1126/science.

abg5332.

32. Reinke, B.A., Cayuela,H., Janzen, F.J., Lemaître, J.F.,

Gaillard, J.M., Lawing, A.M., Iverson, J.B., Christian-

sen, D. G., Martínez-Solano, I., Sánchez-Montes, G.,

Gutiérrez-Rodríguez, J., Rose, F. L., Nelson, N., Ke-

all,S., Crivelli, A.J., Nazirides,T., Grimm-Seyfarth,A.,

Henle,K., Mori, E., Guiller,G., Homan, R., Olivier,A.,

Muths,E., Hossack, B. R., Bonnet, X., et al. (2022) Di-

verse aging rates in ectothermic tetrapods provide in-

sights for the evolution of aging and longevity, Science,

376, 1459-1466, doi:10.1126/science.abm0151.

33. Skulachev, V. P., Holtze, S., Vyssokikh, M. Y., Bakee-

va, L.E., Skulachev, M.V., Markov, A.V., Hildebrandt,

T.B., and Sadovnichii, V.A. (2017) Neoteny, prolonga-

tion of youth: From naked mole rats to “naked apes”

(humans), Physiol. Rev., 97, 699-720, doi: 10.1152/

physrev.00040.2015.

34. Skulachev, V.P., Shilovsky, G.A., Putyatina, T.S., Pop-

ov, N.A., Markov, A.V., Skulachev, M.V., and Sadovni-

chii, V. A. (2020) Perspectives of Homo sapiens lifes-

pan extension: focus on external or internal resourc-

es? Aging (Albany NY), 12, 5566-5584, doi: 10.18632/

aging.102981.

35. Wilkinson, P. M., Rainwater, T. R., Woodward, A. R.,

Leone, E.H., and Carter,C. (2016) Determinate growth

and reproductive lifespan in the American alliga-

tor (Alligator mississippiensis): evidence from long-

term recaptures, Copeia, 104, 843-852, doi: 10.1643/

CH-16-430.

36. Moreira, M.O., Qu, Y.F., and Wiens, J.J. (2021) Large-

scale evolution of body temperatures in land verte-

brates, Evol. Lett., 5, 484-494, doi:10.1002/evl3.249.

37. Clarke, A., and Pörtner, H. O. (2010) Temperature,

metabolic power and the evolution of endother-

my, Biol. Rev., 85, 703-727, doi: 10.1111/j.1469-185X.

2010.00122.x.

38. Skulachev, M. V., Severin, F. F., and Skulachev, V. P.

(2015) Aging as an evolvability-increasing program

which can be switched off by organism to mobilize

additional resources for survival, Curr. Aging Sci.,

8, 95-109, doi:10.2174/1874609808666150422122401.

39. Skulachev, V.P., Vyssokikh, M.Y., Chernyak, B.V., Aver-

ina, O.A., Andreev-Andrievskiy, A.A., Zinovkin, R.A.,

Lyamzaev, K.G., Marey, M.V., Egorov, M.V., Frolova,

O.J., Zorov, D. B., Skulachev, M. V., and Sadovnichii,

V.A. (2023) Mitochondrion-targeted antioxidant SkQ1

prevents rapid animal death caused by highly di-

verse shocks, Sci. Rep., 13, 4326, doi: 10.1038/s41598-

023-31281-31289.

40. Skulachev, V. P., Vyssokikh, M. Y., Chernyak, B. V.,

Mulkidjanian, A.Y., Skulachev, M.V., Shilovsky, G.A.,

Lyamzaev, K. G., Borisov, V.B., Severin, F.F., and Sa-

dovnichii, V. A. (2023) Six functions of respiration:

isn’t it time to take control over ROS production in

mitochondria, and aging along with it? Int.J. Mol. Sci.,

24, 12540, doi:10.3390/ijms241612540.

41. Patnaik, B. K. (1994) Ageing in reptiles, Gerontology,

40, 200-220, doi:10.1159/000213588.

42. Alvarez, J. A., and Vaupel, J. W. (2023) Mortality as

a function of survival, Demography, 60, 327-342,

doi:10.1215/00703370-10429097.

43. da Silva, R., Conde, D. A., Baudisch, A., and Colche-

ro, F. (2022) Slow and negligible senescence among

testudines challenges evolutionary theories of senes-

cence, Science, 376, 1466-1470, doi: 10.1126/science.

abl7811.

44. Frýdlová, P., Mrzílková, J., Šeremeta, M., Křemen, J.,

Dudák, J., Žemlička, J., Minnich, B., Kverková, K.,

Němec, P., Zach, P., and Frynta, D. (2020) Determi-

SHILOVSKY et al.338

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

nate growth is predominant and likely ancestral in

squamate reptiles, Proc. Biol. Sci., 287, 20202737,

doi:10.1098/rspb.2020.2737.

45. Sparkman, A.M., Arnold, S.J., and Bronikowski, A.M.

(2007) An empirical test of evolutionary theories for

reproductive senescence and reproductive effort in

the garter snake Thamnophis elegans, Proc. Biol. Sci.,

274, 943-950, doi:10.1098/rspb.2006.0072.

46. Kara, T.C. (1994) Ageing in amphibians, Gerontology,

40, 161-173, doi:10.1159/000213585.

47. Jiang, Y., Zhao,L., Luan,X., and Liao, W. (2022) Geo-

graphical variation in body size and the Bergmann’s

rule in Andrew’s toad (Bufo andrewsi), Biology (Basel),

11, 1766, doi:10.3390/biology11121766.

48. Miller, J.K. (2001) Escaping senescence: demographic

data from the three-toed box turtle (Terrapene caroli-

na triunguis), Exp. Gerontol., 36, 829-832.

49. Warner, D. A., Miller, D. A., Bronikowski, A. M., and

Janzen, F. J. (2016) Decades of field data reveal that

turtles senesce in the wild, Proc. Natl. Acad. Sci. USA,

113, 6502-6507, doi:10.1073/pnas.1600035113.

50. Bronikowski, A.M., Hedrick, A.R., Kutz, G.A., Hold-

en, K.G., Reinke,B., and Iverson, J.B. (2023) Sex-spe-

cific innate immunity and ageing in long-lived fresh

water turtles (Kinosternon flavescens: Kinostern-

idae), Immun. Ageing, 20, 11, doi: 10.1186/s12979-

023-00335-x.

51. Cayuela, H., Akani, G. C., Hema, E. M., Eniang, E. A.,

Amadi,N., Ajong, S.N., Dendi,D., Petrozzi,F., and Lu-

iselli, L. (2019) Life history and age-dependent mor-

tality processes in tropical reptiles, Biol. J. Linn. Soc.

Lond., 128, 251-262, doi:10.1093/biolinnean/blz103.

52. Shilovsky, G. A., Putyatina, T. S., Markov, A. V., and

Skulachev, V. P. (2015) Contribution of quantitative

methods of estimating mortality dynamics to explain-

ing mechanisms of aging, Biochemistry (Moscow),

80, 1547-1559, doi:10.1134/S0006297915120020.

53. Shilovsky, G.A., Putyatina, T.S., Ashapkin, V.V., Luch-

kina, O.S., and Markov, A.V. (2017) Coefficient of vari-

ation of lifespan across the tree of life: is it a signa-

ture of programmed aging? Biochemistry (Moscow),

82, 1480-1492, doi:10.1134/S0006297917120070.

54. Gavrilova, N. S., Gavrilov, L. A., Severin, F. F., and

Skulachev, V.P. (2012) Testing predictions of the pro-

grammed and stochastic theories of aging: compari-

son of variation in age at death, menopause, and sex-

ual maturation, Biochemistry (Moscow), 77, 754-760,

doi:10.1134/S0006297912070085.

55. Finch, C.E., and Tanzi, R.E. (1997) Genetics of aging, Sci-

ence, 278, 407-411, doi:10.1126/science.278.5337.407.

56. Bronikowski, A.M. (2008) The evolution of aging phe-

notypes in snakes: a review and synthesis with new

data, Age (Dordr)

, 30, 169-176, doi: 10.1007/s11357-

008-9060-5.

57. Robert, K.A., and Bronikowski, A.M. (2010) Evolution

of senescence in nature: physiological evolution in

populations of garter snake with divergent life histo-

ries, Am. Nat., 175, 147-159, doi:10.1086/649595.

58. Olsson,M., Wapstra,E., and Friesen,C. (2018) Ectother-

mic telomeres: it’s time they came in from the cold,

Philos. Trans. R. Soc. Lond. B Biol. Sci., 373, 20160449,

doi:10.1098/rstb.2016.0449.

59. Holtze, S., Gorshkova, E., Braude, S., Cellerino, A.,

Dammann, P., Hildebrandt, T. B., Hoeflich, A., Hoff-

mann,S., Koch,P., Terzibasi Tozzini,E., Skulachev,M.,

Skulachev, V. P., and Sahm, A. (2021) Alternative an-

imal models of aging research, Front. Mol. Biosci.,

8, 660959, doi:10.3389/fmolb.2021.660959.

60. Omotoso, O., Gladyshev, V. N., and Zhou, X. (2021)

Lifespan extension in long-lived vertebrates rooted in

ecological adaptation, Front. Cell. Dev. Biol., 9, 704966,

doi:10.3389/fcell.2021.704966.

61. Botha,J., Weiss, B.M., Dollman,K., Barrett, P.M., Ben-

son, R.B.J., and Choiniere, J.N. (2023) Origins of slow

growth on the crocodilian stem lineage, Curr. Biol.,

8, 4261-4268.e3, doi:10.1016/j.cub.2023.08.057.

62. Ripple, W. J., Newsome, T. M., Wolf, C., Dirzo, R.,

Everatt, K. T., Galetti, M., Hayward, M. W., Kerley,

G. I., Levi, T., Lindsey, P. A., Macdonald, D. W., Mal-

hi, Y., Painter, L. E., Sandom, C. J., Terborgh, J., and

Van Valkenburgh, B. (2015) Collapse of the world’s

largest herbivores, Sci. Adv., 1, e1400103, doi:10.1126/

sciadv.1400103.

63. Fraser,D., Villasenor,A., Toth, A.B., Balk, M.A., Eronen,

J.T., Andrew Barr,W., Behrensmeyer, A.K., Davis,M.,

Du,A., Tyler Faith,J., Graves, G.R., Gotelli, N.J., Jukar,

A.M., Looy, C.V., McGill, B.J., Miller, J.H., Pineda-Mu-

noz,S., Potts,R., Shupinski, A.B., Soul, L.C., and Kath-

leen Lyons,S. (2022) Late quaternary biotic homoge-

nization of North American mammalian faunas, Nat.

Commun., 13, 3940, doi:10.1038/s41467-022-31595-8.

64. Stockdale, M.T., and Benton, M.J. (2021) Environmen-

tal drivers of body size evolution in crocodile-line

archosaurs, Commun. Biol., 4, 38, doi:10.1038/s42003-

020-01561-5.

65. Legendre, L. J., Guénard, G., Botha-Brink, J., and

Cubo, J. (2016) Palaeohistological evidence for an-

cestral high metabolic rate in archosaurs, Syst. Biol.,

65, 989-996, doi:10.1093/sysbio/syw033.

66. Wiemann,J., Menéndez,I., Crawford, J.M., Fabbri,M.,

Gauthier, J. A., Hull, P. M., Norell, M. A., and Briggs,

D. E. G. (2022) Fossil biomolecules reveal an avian

metabolism in the ancestral dinosaur, Nature, 606,

522-526, doi:10.1038/s41586-022-04770-6.

67. Schmalhausen, I. I. (1982) Organism as a whole in its

individual and historic development, in Izbrannye tru-

dy (Selected works) [In Russian], Nauka, Moscow.

68. Edmonds,D., Dreslik, M.J., Lovich, J.E., Wilson, T.P.,

and Ernst, C. H. (2021) Growing as slow as a turtle:

unexpected maturational differences in a small, long-

lived species, PLoS One, 16, e0259978, doi: 10.1371/

journal.pone.0259978.

EVOLUTION OF LONGEVITY AS A SPECIES-SPECIFIC TRAIT 339

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

69. Omeyer, L. C. M., Fuller, W. J., Godley, B. J., Snape,

R.T.E., and Broderick, A.C. (2018) Determinate or in-

determinate growth? Revisiting the growth strategy

of sea turtles, Marine Ecol. Progr. Ser., 596, 199-211,

doi:10.3354/meps12570.

70. Hariharan, I.K., Wake, D.B., and Wake, M.H. (2015)

Indeterminate growth: could it represent the ances-

tral condition? Cold Spring Harb. Perspect. Biol., 8,

a019174, doi:10.1101/cshperspect.a019174.

71. Derocher, A.E., and Wiig,O. (2002) Postnatal growth

in body length and mass of polar bears (Ursus mari-

timus) at Svalbard, J.Zool., 256, 343-349, doi:10.1017/

S0952836902000377.

72. McKenzie, J., Page, B., Goldsworthy, S. D., and Hin-

dell, M. A. (2007) Growth strategies of New Zealand

fur seals in southern Australia, J. Zool., 272, 377-389,

doi:10.1111/j.1469-7998.2006.00278.x.

73. Mumby, H.S., Chapman, S.N., Crawley, J.A.H., Mar,

K.U., Htut,W., Soe, A.T., Aung, H.H., and Lummaa,V.

(2015) Distinguishing between determinate and inde-

terminate growth in a long-lived mammal, BMC Evol.

Biol., 15, 214, doi:10.1186/s12862-015-0487-x.

74. Shine, R., and Charnov, E. L. (1992) Patterns of sur-

vival, growth, and maturation in snakes and lizards,

Am. Naturalist, 139, 1257-1269, doi:10.1086/285385.

75. Shine,R., and Iverson, J.B. (1995) Patterns of survival,

growth and maturation in turtles, Oikos, 72, 343-348,

doi:10.2307/3546119.

76. Harris, R.J., and Arbuckle,K. (2016) Tempo and mode

of the evolution of venom and poison in tetrapods,

Toxins (Basel), 8, 193, doi:10.3390/toxins8070193.

77. Stark,G. (2022) Large and expensive brain comes with

a short lifespan: the relationship between brain size

and longevity among fish taxa, J.Fish. Biol., 101, 92-99,

doi:10.1111/jfb.15074.

78. Stark,G., and Pincheira-Donoso,D. (2022) The evolu-

tion of brain size in ectothermic tetrapods: large brain

mass trades-off with lifespan in reptiles, Evol. Biol.,

49, 180-188, doi:10.1007/s11692-022-09562-4.

79. Yu, X., Zhong, M. J., Li, D. Y., Jin, L., Liao, W. B., and

Kotrschal,A. (2018) Large-brained frogs mature later

and live longer, Evolution, 72, 1174-1183, doi:10.1111/

evo.13478.

80. Skulachev, V. P. (1997) Aging is a specific biological

function rather than the result of a disorder in com-

plex living systems: biochemical evidence in support

of Weismann’s hypothesis, Biochemistry (Moscow),

62, 1191-1195.

81. Lidsky, P.V., Yuan,J., Rulison, J.M., and Andino-Pav-

lovsky, R. (2022) Is aging an inevitable character-

istic of organic life or an evolutionary adaptation?

Biochemistry (Moscow), 87, 1413-1445, doi: 10.1134/

S0006297922120021.

82. Bronikowski,A., and Vleck,D. (2010) Metabolism, body

size and life span: a case study in evolutionarily di-

vergent populations of the garter snake (Thamnophis

elegans), Integr. Comp. Biol., 50, 880-887, doi:10.1093/

icb/icq132.

83. Dammann, P., Šaffa,G., and Šumbera,R. (2022) Lon-

gevity of a solitary mole-rat species and its implica-

tions for the assumed link between sociality and lon-

gevity in African mole-rats (Bathyergidae), Biol. Lett.,

18, 20220243, doi:10.1098/rsbl.2022.0243.

84. Burgin, C.J., Colella, J.P., Kahn, P.L., and Upham, N.S.

(2018) How many species of mammals are there?

J.Mammal., 99, 1-14, doi:10.1093/jmammal/gyx147.

85. Giaimo,S., and Traulsen,A. (2022) The selection force

weakens with age because ageing evolves and not

vice versa, Nat. Commun., 13, 686, doi:10.1038/s41467-

022-28254-3.

86. Prum, R. O., Berv, J. S., Dornburg, A., Field, D. J.,

Townsend, J. P., Lemmon, E. M., and Lemmon, A. R.

(2015) A comprehensive phylogeny of birds (Aves) us-

ing targeted next-generation DNA sequencing, Nature,

526, 569-573, doi:10.1038/nature15697.

87. Rotger,A., Tenan,S., Igual, J. M., Bonner,S., and Tav-

ecchia, G. (2023) Life span, growth, senescence and

island syndrome: Accounting for imperfect detection

and continuous growth, J. Anim. Ecol., 9, 183-194,

doi:10.1111/1365-2656.13842.

88. Van Schaik, C.P., Song,Z., Schuppli,C., Drobniak, S.M.,

Heldstab, S. A., and Griesser, M. (2023) Extended pa-

rental provisioning and variation in vertebrate brain

sizes, PLoS Biol., 21, e3002016, doi: 10.1371/journal.

pbio.3002016.

89. Sacher, G. A. (1968) Molecular versus systemic theo-

ries on the genesis of ageing, Exp. Gerontol., 3, 265-271,

doi:10.1016/0531-5565(68)90011-9.

90. Knope, M.L., Bush, A.M., Frishkoff, L.O., Heim, N.A.,

and Payne, J. L. (2020) Ecologically diverse clades

dominate the oceans via extinction resistance, Science,

367, 1035-1038, doi:10.1126/science.aax6398.

91. Lewis, K. N., Wason, E., Edrey, Y. H., Kristan, D. M.,

Nevo, E., and Buffenstein, R. (2015) Regulation of

Nrf2 signaling and longevity in naturally long-lived

rodents, Proc. Natl. Acad. Sci. USA, 112, 3722-3727,

doi:10.1073/pnas.1417566112.

92. Shilovsky, G. A., Shram, S. I., Morgunova, G. V., and

Khokhlov, A. N. (2017) Protein poly(ADP-ribosyl)

ation system: Changes in development and aging as

well as due to restriction of cell proliferation, Bio-

chemistry (Moscow), 82, 1391-1401, doi: 10.1134/

S0006297917110177.

93. Shilovsky, G. A. (2022) Lability of the Nrf2/Keap/ARE

cell defense system in different models of cell aging

and age-related pathologies, Biochemistry (Moscow),

87, 70-85, doi:10.1134/S0006297922010060.

94. Jové,M., Mota-Martorell,N., Fernàndez-Bernal,A., Por-

tero-Otin,M., Barja,G., and Pamplona,R. (2023) Phe-

notypic molecular features of long-lived animal spe-

cies, Free Radic. Biol. Med., 208, 728-747, doi:10.1016/

j.freeradbiomed.2023.09.023.

SHILOVSKY et al.340

BIOCHEMISTRY (Moscow) Vol. 89 No. 2 2024

95. Rafikova, E., Nemirovich-Danchenko, N., Ogmen, A.,

Parfenenkova, A., Velikanova, A., Tikhonov, S., Pe-

shkin, L., Rafikov, K., Spiridonova, O., Belova,Y., Gli-

nin,T., Egorova,A., and Batin,M. (2023) Open Genes–

a new comprehensive database of human genes as-

sociated with aging and longevity, Nucleic Acids Res.,

52, gkad712, doi:10.1093/nar/gkad712.

96. Vyssokikh, M.Y., Holtze,S., Averina, O.A., Lyamzaev,

K.G., Panteleeva, A. A., Marey, M.V., Zinovkin, R.A.,

Severin, F.F., Skulachev, M.V., Fasel,N., Hildebrandt,

T.B., and Skulachev, V.P. (2020) Mild depolarization of

the inner mitochondrial membrane is a crucial com-

ponent of an antiaging program, Proc. Natl. Acad. Sci.

USA, 117, 64916501, doi:10.1073/pnas.1916414117.

97. Odeh,A., Eddini,H., Shawasha,L., Chaban,A., Avivi,A.,

Shams, I., and Manov, I. (2023) Senescent secretome

of blind mole rat Spalax inhibits malignant behavior

of human breast cancer cells triggering bystander se-

nescence and targeting inflammatory response, Int. J.

Mol. Sci., 24, 5132, doi:10.3390/ijms24065132.

98. Yakovleva, E. U., Naimark, E. B., and Markov, A. V.

(2016) Adaptation of Drosophila melanogaster to un-

favorable growth medium affects lifespan and age-

related fecundity, Biochemistry (Moscow), 81, 1445-

1460, doi:10.1134/S0006297916120063.

99. Jacobs, P.J., Hart, D.W., Merchant, H.N., Voigt,C., and

Bennett, N. C. (2023) The evolution and ecology of

oxidative and antioxidant status: a comparative ap-

proach in African mole-rats, Antioxidants (Basel), 12,

1486, doi:10.3390/antiox12081486.

100. Tyshkovskiy, A., Ma, S., Shindyapina, A. V., Tikhon-

ov, S., Lee, S. G., Bozaykut, P., Castro, J. P., Seluan-

ov, A., Schork, N. J., Gorbunova, V., Dmitriev, S. E.,

Miller, R.A., and Gladyshev, V.N. (2023) Distinct lon-

gevity mechanisms across and within species and

their association with aging, Cell, 186, 2929-2949.e20,

doi:10.1016/j.cell.2023.05.002.

101. Grosfeld, E. V., Bidiuk, V. A., Mitkevich, O. V., Gha-

zy, E.S.M. O., Kushnirov, V.V., and Alexandrov, A.I.

(2021) A systematic survey of characteristic features

of yeast cell death triggered by external factors, J. Fun-

gi (Basel), 7, 886, doi:10.3390/jof7110886.

102. Khan, I., Yousif, A., Chesnokov, M., Hong, L., and

Chefetz, I. (2021) A decade of cell death studies:

breathing new life into necroptosis, Pharmacol. Ther.,

220, 107717, doi:10.1016/j.pharmthera.2020.107717.

Publisher’s Note. Pleiades Publishing remains

neutral with regard to jurisdictional claims in pub-

lished maps and institutional affiliations.