Diapause and aging: Two opposing yet intertwined biological phenomena

Diapause is an evolutionarily conserved strategy that enables many organisms to survive prolonged exposure to harsh environmental stressors. During this state, organisms drastically reduce their metabolic rate, halt development, and enhance stress tolerance in an energy-efficient manner. Remarkably, many diapausing organisms appear to substantially slow or suspend aging as a result of profound metabolic depression and developmental arrest. Consequently, diapause and aging appear to be programmed in opposite directions, yet both rely on many of the same master regulatory genes and epigenetic modulators. This review explores the molecular mechanisms underlying diapause-induced stress resistance and metabolic suppression, offering critical insights into how dormant biological systems preserve function and delay aging. Manipulating these shared regulatory networks has led to significant extensions in lifespan and improvements in healthspan across various model organisms. Anhydrobiotic species such as Artemia, Caenorhabditis elegans, and tardigrades can nearly suspend aging during dormancy by downregulating metabolic pathways and accumulating protective macromolecules. Notably, the African turquoise killifish, which has adapted to life in ephemeral ponds, can provide a unique platform to study both diapause and aging within a single vertebrate model. Phenotypic plasticity may offer the most compelling evolutionary explanation for resolving the paradox of how the same regulatory network can produce opposite outcomes in diapause and aging. Overall, diapause offers a powerful natural framework for uncovering anti-aging mechanisms and holds great promise for guiding the development of novel interventions to promote longevity and healthy aging.