Genetic insights from long-lived mammals

Importance: As human and companion animal lifespans increase, understanding the biological basis of aging is becoming critical in human and veterinary medicine.Longlived animals, such as naked mole-rats, elephants, bats, whales, and hibernating squirrels, offer powerful models to explore the natural mechanisms of longevity.Their unique adaptations provide valuable insights into delaying age-related decline and improving the lifespans across species.Observations: This review highlights the conserved signaling pathways associated with longevity, including mTOR, SIRT1, FOXO3a, Nrf2, HIF-1, and p16/p21.These pathways influence oxidative stress, mitochondrial function, DNA repair, and tumor suppression.Species-specific adaptations further improve understanding: elephants possess multiple TP53 copies; bats maintain telomere stability; whales suppress mutagenesis; hibernating squirrels regulate inflammation seasonally.Even dogs and cats have breed-specific aging markers and serve as practical models for translational aging research.Shared traits, such as stress resistance, metabolic flexibility, and social complexity, appear to be closely linked to extended lifespans.Conclusions and Relevance: Long-lived species provide essential clues for healthy aging.Their unique molecular genetics and ecological strategies defy conventional aging paradigms and point to innovative avenues for intervention.Thus, integrating evolutionary and genomic insights may provide holistic approaches to age-related disease prevention in humans and animals.