Comparative transcriptomics and methylomics of rejuvenation capacity across six animal species

Authors

  • David Aphkhazava PhD, Professor, University of Georgia, Tbilisi, Georgia. Orcid: https://orcid.org/0000- 0001- 6216-64
  • Maia Nozadze PhD, Professor, University of Georgia, Tbilisi, Georgia
  • Mzia Tsiklauri PhD, Affiliated Professor of the Medical Programs of Gr.Robakidze University, Microbiology, Immunology, Virology, Infection Control. Invited Professor of the Medical Programs of Alte University, Tbilisi, Georgia. Invited Professor of the Medical Programs of Caucasus International University, Laboratory Medicine, Tbilisi, Georgia. Member of the Georgian Immunologists Association, Member of the Accreditation Council of the Quality Development, Center of the Ministry of Education of Georgia
  • Manana Makharadze Prof. David Agmashenebeli University of Georgia, Tbilisi, Georgia.
  • Maia Berodze Assistant Professor at Caucasus International University, Tbilisi, Georgia
  • Nodar Sulashvili MD, PhD, Doctor of Pharmaceutical and Pharmacological Sciences In Medicine, Invited Lecturer (Professor) of Scientific Research-Skills Center at Tbilisi State Medical University; Professor of Medical and Clinical Pharmacology of International School of Medicine at Alte University; Professor of Pharmacology of Faculty of Medicine at Georgian National University SEU, Associate Affiliated Professor of Medical Pharmacology of Faculty of Medicine at Sulkhan-Saba Orbeliani University; Associate Professor of Medical Pharmacology at School of Medicine at David Aghmashenebeli University of Georgia; Associate Professor of Biochemistry and Pharmacology Direction of School of Health Sciences at the University of Georgia. Associate Professor of Pharmacology of Faculty Dentistry and Pharmacy at Tbilisi Humanitarian Teaching University; Tbilisi, Georgia; Orcid: https://orcid.org/0000-0002-9005-8577.
  • Giorgi Margvelani Prof. European University, Tbilisi, Georgia.
  • Anushka Rohidas Temgire Alte University, Tbilisi, Georgia
  • Arfan Imtiaz Abdul Samad University of Georgia, Tbilisi, Georgia
  • Tharushi Anargali Silva Alte University, Tbilisi, Georgia
  • Oluwadamilola Pentho Nudegbesi Alte University, Tbilisi, Georgia
  • Muskan Khan Alte University, Tbilisi, Georgia
  • Vedant Anilkumar Malekar Alte University, Tbilisi, Georgia
  • Aayushi Thakur University of Georgia, Tbilisi, Georgia
  • Janhavi Deepak Doshi Alte University, Tbilisi, Georgia
  • Nino Maziashvili Associate Professor, University of Georgia, Tamar Gagoshidze Neuropsychology Center, Tbilisi, Georgia
  • Lolita Shengelia PhD, Invited lecturer of Georgian National University, Tbilisi, Georgia; Invited lecturer of Georgian American University, Tbilisi, Georgia
  • George Maglakelidze PhD, Professor, University of Georgia, Tbilisi, Georgia
  • Ilia Atanelishvili Medical University of South Carolina, Charleston, SC, USA

Keywords:

comparative transcriptomics, aging, rejuvenation, partial reprogramming, naked mole rat, bowhead whale, turquoise killifish, axolotl, Hydra, DNA methylation clock, single-cell RNA sequencing, inflammation, genome maintenance, stem cells

Abstract

Organisms differ dramatically in how they age, from the compressed few-month lifespan of the turquoise killifish to the apparent absence of demographic aging in Hydra, yet the molecular basis of these differences remains poorly defined. We present a unified comparative analysis of aging and rejuvenation programs across six species representing extreme points of the lifespan distribution: the laboratory mouse, the naked mole rat, the bowhead whale, the African turquoise killifish, the axolotl, and the freshwater polyp Hydra. We generated 208 bulk RNA-sequencing libraries from liver, skin, skeletal muscle and brain (plus regenerating limb blastema in the axolotl), mapped expression onto 3,914 strict single-copy orthogroups, and supplemented these data with reduced-representation bisulfite sequencing and reanalysis of four published single-cell atlases. Age-associated transcriptional drift, measured as the median orthogonal shift in orthologous gene expression between young and old individuals, segregated species into two broad classes: high-drift species (mouse and killifish) and low-drift species (naked mole rat, bowhead whale, axolotl and Hydra). A conserved inflammation and extracellular-matrix module that expands with age in mouse and killifish remained stable in all four low-drift species, and a mitochondrial module that declines with age in short-lived species was preserved in the naked mole rat and the bowhead whale. Reanalysis of an inducible reprogramming study showed that 64.7% of mouse liver aging genes returned toward the young direction after seven weeks of cyclic OSKM expression, and orthologs of these reversibly regulated genes were significantly enriched among age-stable genes in resilient species. DNA repair pathway scores were highest in bowhead whale, naked mole rat, axolotl and Hydra, and pan-mammalian epigenetic clock predictions revealed near-zero annualized drift in Hydra and the lowest age acceleration in the bowhead whale. Single-cell reanalysis confirmed that cell identity is preserved in the naked mole rat but eroded in mouse and killifish. A composite rejuvenation capacity index, built from seven pillars, ranked the species in the order Hydra, axolotl, bowhead whale, naked mole rat, mouse and killifish, and correlated strongly with lifespan but not body size. We conclude that rejuvenation capacity is a modular, evolutionarily conserved property of genomes that is partially independent of lifespan, and that the targets of experimentally induced rejuvenation overlap with the constitutively stable programs of resilient species.

Published

2026-09-06

How to Cite

David Aphkhazava, Maia Nozadze, Mzia Tsiklauri, Manana Makharadze, Maia Berodze, Nodar Sulashvili, Giorgi Margvelani, Anushka Rohidas Temgire, Arfan Imtiaz Abdul Samad, Tharushi Anargali Silva, Oluwadamilola Pentho Nudegbesi, Muskan Khan, Vedant Anilkumar Malekar, Aayushi Thakur, Janhavi Deepak Doshi, Nino Maziashvili, Lolita Shengelia, George Maglakelidze, & Ilia Atanelishvili. (2026). Comparative transcriptomics and methylomics of rejuvenation capacity across six animal species. Reviews of Modern Science, (14). Retrieved from https://ojs.publisher.agency/index.php/RMS/article/view/9247

Issue

No. 14 (2026): Reviews of Modern Science

Section

Biological Sciences

License

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