Lifespan

Lifespan is the total length of life, and understanding ageing and the processes that limit lifespan has challenged biologists for several decades. ^[1] It is distinct from healthspan: dietary restriction, for example, delays ageing and extends both healthspan and lifespan, indicating the two are related but separate outcomes. ^[2]

The biology of ageing gained scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. ^[1] Large-scale genome-wide association studies have identified many loci that influence key human ageing traits, including lifespan, and mutations that drive accelerated ageing in progeria syndromes point to an important role for genome maintenance and stability. ^[3]

The past two centuries have witnessed an unprecedented rise in human life expectancy, and sustaining longer lives with reduced periods of disability will require an understanding of the underlying mechanisms of ageing. ^[3] Strategies to extend health span and life span require an understanding of interindividual differences in age-dependent functional decline, known as biological aging. ^[4]

The restriction of calories, branched-chain amino acids, and methionine have all been shown to extend lifespan in model organisms, and glycine was found to boost longevity in genetically heterogenous mice and extend lifespan in rats. ^[5] Senotherapies such as senolytic and senomorphic drugs, stem cell therapies and other interventions have been shown to extend lifespan and reduce tissue injury in various animal models. ^[6] Early clinical trials confirm that senotherapeutic approaches could be beneficial in human disease, but larger clinical trials are needed to translate these approaches to patient care. ^[6]