# Aging is not a disease: an evolutionary and comparative biological reappraisal

**Authors:** Bruno César Feltes

PMC · DOI: 10.1007/s10522-026-10422-3 · 2026-03-23

## TL;DR

This paper argues that aging should not be classified as a disease, based on evolutionary and comparative biological evidence.

## Contribution

It provides a reappraisal of aging through evolutionary and comparative biology, challenging the disease classification.

## Key findings

- Aging is an emergent consequence of evolutionary trade-offs, not a deviation from normal function.
- Molecular processes linked to aging are conserved and context-dependent, not consistently pathological.
- Epigenetic clocks track biological aging but do not indicate an underlying disease process.

## Abstract

The question of whether aging should be classified as a disease has gained prominence in geroscience, fueled by advances in molecular biology and the aspiration to develop interventions that mitigate age-associated functional decline. However, evolutionary models describe aging as an emergent consequence of declining selection gradients and life-history trade-offs rather than as a deviation from species-typical function. Comparative data across taxa reveal substantial heterogeneity in aging trajectories, challenging the assumption of a uniform pathological pattern. At the molecular level, processes often described as “hallmarks of aging” reflect conserved regulatory mechanisms whose effects are context-dependent and do not consistently align with criteria used to define diseases. Likewise, epigenetic clocks capture molecular signatures that track biological aging and predict mortality risk, yet these biomarkers reflect time-dependent molecular remodeling rather than an underlying pathological process. While translational research aimed at extending healthspan has generated important advances, current empirical evidence does not support equating aging with disease in a strict biological sense. Even though the classification of aging is not relevant to the importance of investing in aging research to alleviate its burden, maintaining a clear conceptual distinction between time-dependent biological remodeling and pathological dysfunction may provide a more coherent basis for both scientific inquiry and therapeutic development.

## Full-text entities

- **Genes:** TOP2B (DNA topoisomerase II beta) [NCBI Gene 7155] {aka BILU, TOPIIB, top2beta}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}
- **Diseases:** dementia (MESH:D003704), autoimmune diseases (MESH:D001327), non-communicable disease (MESH:D000073296), metabolic disorders (MESH:D008659), chronic (MESH:D002908), Neoplasia (MESH:D009369), age-related diseases (MESH:D010024), heart failure (MESH:D006333), chronic inflammation (MESH:D007249), kidney failure (MESH:D051437), infections (MESH:D007239), Injuries (MESH:D014947), metastasis (MESH:D009362), Aging (MESH:D019588), Diseases (MESH:D004194), obese (MESH:D009765), cytotoxic (MESH:D064420), cardiovascular disease (MESH:D002318), frailty (MESH:D000073496), mitochondrial dysfunction (MESH:D028361), diabetes (MESH:D003920), neurodegeneration (MESH:D019636), osteoarthritis (MESH:D010003)
- **Chemicals:** NAD+ (MESH:D009243), reactive oxygen species (MESH:D017382), pyruvate (MESH:D019289), rapamycin (MESH:D020123), ketone body (MESH:D007657)
- **Species:** PX clade (clade) [taxon 569578], Homo sapiens (human, species) [taxon 9606]

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Source: https://tomesphere.com/paper/PMC13009041