Biological resilience and aging: Activation of stress response pathways contributes to lifespan extension

While aging was traditionally viewed as a stochastic process of damage accumulation, it is now clear that aging is strongly influenced by genetics. The identification and characterization of long-lived genetic mutants in model organisms has provided insights into the genetic pathways and molecular mechanisms involved in extending longevity. Long-lived genetic mutants exhibit activation of multiple stress response pathways leading to enhanced resistance to exogenous stressors. As a result, lifespan exhibits a significant, positive correlation with resistance to stress. Disruption of stress response pathways inhibits lifespan extension in multiple long-lived mutants representing different pathways of lifespan extension and can also reduce the lifespan of wild-type animals. Combined, this suggests that activation of stress response pathways is a key mechanism by which long-lived mutants achieve their extended longevity and that many of these pathways are also required for normal lifespan. These results highlight an important role for stress response pathways in determining the lifespan of an organism.

Automated summary

While aging was once considered as a stochastic process of damage accumulation, recent studies have shown that genetics plays a significant role in the aging process. Long-lived genetic mutants in model organisms have provided insights into the genetic and molecular mechanisms involved in extending lifespan. These mutants exhibit activation of stress response pathways, leading to enhanced resistance to stressors, and lifespan exhibits a positive correlation with stress resistance. Disruption of stress response pathways inhibits lifespan extension in these mutants and also reduces lifespan in normal animals, indicating the crucial role of stress response pathways in determining lifespan.