From cave adaptation to ageing resilience: the Mexican cavefish Astyanax mexicanus.

Abstract

The Mexican cavefish, Astyanax mexicanus, is a powerful evolutionary model for investigating how adaptation to extreme environments reshapes vertebrate physiology. Multiple cave populations have independently evolved under subterranean conditions, acquiring traits including insulin resistance, persistent hyperglycaemia, increased adiposity, altered sleep patterns, hypoxia tolerance and extensive metabolic reprogramming. Despite these differences, cavefish exhibit lifespans comparable to those of surface fish, while selected traits, including fertility and locomotor performance, appear to be better preserved with age. These observations challenge the assumption that persistent metabolic dysfunction necessarily entails accelerated functional decline and raise the possibility that cavefish have evolved mechanisms of ageing resilience. This narrative review examines evidence linking cave adaptation to biological processes relevant to ageing, focusing on nutrient sensing, lipid metabolism, mitochondrial function, redox homeostasis and immune regulation. Rather than eliminating metabolic stress, cave-associated adaptations may buffer some of its downstream consequences, preserving selected physiological functions. Evidence is evaluated within the framework of the hallmarks of ageing, considering genomic instability, telomere dynamics, deregulated nutrient sensing, mitochondrial dysfunction and chronic inflammation, while identifying major knowledge gaps regarding epigenetic alterations, loss of proteostasis, macroautophagy, cellular senescence, stem-cell exhaustion, altered intercellular communication and dysbiosis. The available evidence supports A. mexicanus as a comparative model for investigating how chronic environmental and metabolic stress can be uncoupled from selected aspects of functional decline. Distinguishing delayed ageing from enhanced tolerance or compensation in response to accumulated damage will be essential to establish the extent and mechanisms of ageing resilience in this species.