# Molecular evolution of animal aging

**Authors:** Daniel H Nussey, Fabrizio d’Adda di Fagagna, Allison J Bardin, Helen M Blau, Anne Brunet, Dmitry V Bulavin, Longhua Guo, Eiji Hara, Jan Philipp Junker, Vera Gorbunova, Maria Mittelbrunn, Michael Rera, Jane Reznick, Andrei Seluanov, Björn Schumacher, Emma C Teeling, Dario Riccardo Valenzano, Jing Ye, Maximina H Yun, George A Garinis, Eric Gilson

PMC · DOI: 10.1038/s44318-026-00725-z · 2026-02-27

## TL;DR

This paper explores how evolution shapes aging and longevity differences across animals.

## Contribution

It provides a unified framework integrating diverse insights on aging mechanisms and evolutionary theories.

## Key findings

- Evolutionary theories of aging remain largely theoretical without molecular mechanisms.
- Comparative biology reveals variability in aging patterns across species.
- A multi-angle view helps explain differences in longevity across animals and environments.

## Abstract

Comparative biology plays a crucial role in uncovering fundamental biological mechanisms and providing evolutionary models for their variation. This approach is particularly valuable for studying aging, given the remarkable diversity in aging trajectories across the tree of life. Many evolutionary theories of aging were proposed well before the discovery of the molecular mechanisms involved, and they remain largely theoretical. Moreover, the growing number of model organisms and the expanding array of experimental and theoretical approaches used to study aging have often remained compartmentalized. As a result, integrating these diverse insights into a unified framework has become increasingly important. As a step toward this goal, this field perspective outlines general biological mechanisms that help explain the variability in aging patterns and longevity across the animal kingdom.

This field perspective explores the impact of evolution on aging and offers a multi-angle view on longevity variation across animals and environments.

## Full-text entities

- **Genes:** GRDX (Graves disease, susceptibility to, X-linked) [NCBI Gene 117189] {aka GD3}, Smurf (SMAD specific E3 ubiquitin protein ligase) [NCBI Gene 36999] {aka CG4943, D-smurf, DSmurf, Dmel\CG4943, Dsmurf, LACK}, TERT (telomerase reverse transcriptase) [NCBI Gene 7015] {aka CMM9, DKCA2, DKCB4, EST2, PFBMFT1, TCS1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, TERF2 (telomeric repeat binding factor 2) [NCBI Gene 7014] {aka TRBF2, TRF2}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, DYRK1A (dual specificity tyrosine phosphorylation regulated kinase 1A) [NCBI Gene 1859] {aka DYRK, DYRK1, HP86, MNB, MNBH, MRD7}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, Hpgd (hydroxyprostaglandin dehydrogenase 15 (NAD)) [NCBI Gene 15446] {aka 15-PGDH}, Ercc1 (excision repair cross-complementing rodent repair deficiency, complementation group 1) [NCBI Gene 13870] {aka Ercc-1}, HPGD (15-hydroxyprostaglandin dehydrogenase) [NCBI Gene 3248] {aka 15-PGDH, PGDH, PGDH1, PHOAR1, SDR36C1}, KCNIP3 (potassium voltage-gated channel interacting protein 3) [NCBI Gene 30818] {aka CSEN, DREAM, KCHIP3}, Tcea1 (transcription elongation factor A (SII) 1) [NCBI Gene 21399] {aka S-II}, Igha (immunoglobulin heavy constant alpha) [NCBI Gene 238447] {aka IgA, Igh-2}, col12a1a (collagen, type XII, alpha 1a) [NCBI Gene 100149543] {aka col12a1}
- **Diseases:** death (MESH:D003643), tumorigenesis (MESH:D063646), progeroid (MESH:C536423), disease (MESH:D004194), retinal degeneration (MESH:D012162), Age (MESH:D019588), decline (MESH:D060825), Heart injury (MESH:D006335), infections (MESH:D007239), stroke (MESH:D020521), photoreceptor (MESH:D012173), degenerative diseases (MESH:D019636), mitochondrial dysfunction (MESH:D028361), hypercapnia (MESH:D006935), cognitive decline (MESH:D003072), locomotor decline (MESH:D001523), muscle (MESH:D019042), immune system abnormalities (MESH:D007154), cardiovascular conditions (MESH:D002318), dysbiosis (MESH:D064806), fibrosis (MESH:D005355), cancer (MESH:D009369), hypoxia (MESH:D000860), chronic (MESH:D002908), loss (MESH:D016388), metabolic disorders (MESH:D008659), organ failure (MESH:D009102), heart attack (MESH:D009203), multiorgan failure (MESH:D051437), TFIIS-defective (MESH:D000013), inborn (MESH:D030342), mitochondrial defects (MESH:C565376), chronic inflammation (MESH:D007249), neuronal (MESH:D009410), Alzheimer's (MESH:D000544), hypoxic (MESH:D002534)
- **Chemicals:** fatty acid (MESH:D005227), oxygen (MESH:D010100), 15-PGDHi (-), prostaglandin (MESH:D011453), sialic acid (MESH:D019158), glycogen (MESH:D006003), harmine (MESH:D006247), glycosphingolipid (MESH:D006028), carbohydrate (MESH:D002241), oligonucleotides (MESH:D009841), PGE2 (MESH:D015232)
- **Species:** Bacillus sp. AT (species) [taxon 1196779], Danio rerio (leopard danio, species) [taxon 7955], Mus musculus (house mouse, species) [taxon 10090], Somniosus microcephalus (Greenland shark, species) [taxon 191813], Myotis (genus) [taxon 9434], Ovis aries (domestic sheep, species) [taxon 9940], Cryptomys hottentotus (African mole rat, species) [taxon 10175], Schmidtea mediterranea (freshwater planarian, species) [taxon 79327], Drosophila melanogaster (fruit fly, species) [taxon 7227], C. elegans [taxon 328850], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Ambystoma mexicanum (axolotl, species) [taxon 8296], Fundulus heteroclitus (Atlantic killifish, species) [taxon 8078], Heterocephalus glaber (naked mole rat, species) [taxon 10181], Chiroptera (bats, order) [taxon 9397], Molossus molossus (Pallas's mastiff bat, species) [taxon 27622], Nothobranchius furzeri (turquoise killifish, species) [taxon 105023], Balaena mysticetus (bowhead, species) [taxon 27602]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13043702/full.md

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Source: https://tomesphere.com/paper/PMC13043702