Enhancing Late-Life Survival and Mobility via Mitohormesis by Reducing Mitochondrial Calcium Levels.

ABSTRACT: Mitochondrial calcium (Ca²⁺) homeostasis plays a critical role in aging and cellular fitness. In the search for novel antiaging approaches, we explored how genetic and pharmacological inhibition of mitochondrial Ca²⁺ uptake influences the lifespan and health of Caenorhabditis elegans. Using live-cell imaging, we demonstrate that RNA interference-mediated knockdown of mcu-1, the nematode ortholog of the mitochondrial Ca²⁺ uniporter (MCU), reduces mitochondrial Ca²⁺ levels, thereby extending lifespan and preserving motility during aging, while compromising early-life survival. This longevity benefit requires intervention before day 14 and coincides with a transient increase in reactive oxygen species (ROS), which activates pathways involving pmk-1,

SUBMITTER: Bresilla D 

PROVIDER: S-EPMC12608091 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature