Progeroid Syndrome with Signs of Autophagy Dysfunction in the Naked Mole Rat (Heterocephalus glaber)

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Vasiliy N. Manskikh^1,a*, Eugene V. Sheval¹, Maria V. Marey², Olga A. Averina¹, and Mikhail Yu. Vyssokikh^1,2

¹A. N. Belozersky Research Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119992 Moscow, Russia

²V. I. Kulakov National Medical Research Center for Obstetrics, Gynecology, and Perinatology, Ministry of Health of the Russian Federation, 117997 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 1, 2025; Revised: November 27, 2025; Accepted: November 27, 2025

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The naked mole rat is considered a unique non-aging mammalian species and is widely used in laboratories to study the biology of longevity. Previously, our group was the first to describe a new fatal disease in the naked mole rat, termed “idiopathic cachexia.” A detailed study of pathological changes in the organs of affected animals, combined with the data on gene expression changes, allows us to interpret this disease as a highly specific variant of accelerated aging (progeroid syndrome or progeria) in these animals. Symptoms of the disease include cachexia, cataracts, lipofuscinosis, and appearance of amyloid bodies (corpora amylacea) in the brain, severe degeneration of cardiomyocytes, fatty degeneration, and generalized lipofuscinosis of the liver and kidneys, with signs of autophagy dysfunction in these organs. Further research is needed to elucidate the mechanism of this disease in animals with negligible aging, such as naked mole rats, which may provide insights into the mechanisms of aging and lifespan extension.

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KEY WORDS: naked mole rat, autophagy, progeria, aging, lipofuscin

DOI: 10.1134/S0006297925601960

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