REVIEW: “Aging Clocks” Based on Cell-Free DNA

---

Aleksandr V. Sergeev^1,2,a*, Olga V. Kisil^1,3, Andrey A. Eremin¹, Aleksandr S. Petrov¹, Maria E. Zvereva¹

¹Faculty of Chemistry, Lomonosov Moscow State University, 119991 Moscow, Russia

²Orekhovich Scientific Research Institute of Biomedical Chemistry, 119121 Moscow, Russia

³Gauze Scientific Research Institute of New Antibiotics, 119021 Moscow, Russia

^* To whom correspondence should be addressed.

Received: August 9, 2024; Revised: October 8, 2024; Accepted: October 17, 2024

---

Aging is associated with systemic changes in the physiological and molecular parameters of the body. These changes are referred to as biomarkers of aging. Statistical models that link changes in individual biomarkers to biological age are called aging clocks. These tools facilitate a comprehensive evaluation of bodily health and permit the quantitative determination of the rate of aging. A particularly promising area for the development of aging clocks is the analysis of cell-free DNA (cfDNA), which is present in the blood and contains numerous potential biomarkers. This review explores in detail the fragmentomics, topology, and epigenetic landscape of cfDNA as possible biomarkers of aging. The review further underscores the potential of leveraging single-molecule sequencing of cfDNA in conjunction with long-read technologies to simultaneously profile multiple biomarkers, a strategy that could lead to the development of more precise aging clocks.

---

KEY WORDS: cfDNA, cell-free nucleic acids, extrachromosomal circular DNA, aging clock, fragmentome, epigenome, methylation, nanopore sequencing

DOI: 10.1134/S0006297924604076

Publisher’s Note. Pleiades Publishing remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

---