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

• Published in: Ageing research reviews 2023-07, Vol.88, p.101941-101941, Article 101941
• Main Authors: Soo, Sonja K., Rudich, Zenith D., Ko, Bokang, Moldakozhayev, Alibek, AlOkda, Abdelrahman, Van Raamsdonk, Jeremy M.
• Format: Article
• Language: English
• Subjects: Aging; Aging - genetics; Animals; Biological resilience; C. elegans; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Genetics; Humans; Lifespan; Longevity - genetics; Oxidative Stress; Stress resistance; Stress response pathways
• ISSN: 1568-1637; 1872-9649
• DOI: 10.1016/j.arr.2023.101941

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. [Display omitted] •Long-lived genetic mutants exhibit activation of multiple stress response pathways.•Stress response pathways are required for the extended longevity of long-lived mutants.•Disruption of stress response pathways can also shorten wild-type lifespan.•Stress response pathways contribute to both stress resistance and lifespan leading to a correlation between these phenotypes.•Activation of stress response pathways is an important mechanism contributing to lifespan extension.