Adult-restricted gene knock-down reveals candidates that affect locomotive healthspan in C. elegans

Understanding how we can age healthily is a challenge at the heart of biogerontological interest. Whereas myriad genes are known to affect the lifespan of model organisms, effects of such interventions on healthspan-the period of life where an animal is considered healthy, rather than merely alive-are less clear. To understand relationships between life- and healthspan, in recent years several platforms were developed with the purpose of assessing both readouts simultaneously. We here relied on one such platform, the WorMotel, to study effects of adulthood-restricted knock-down of 130 Caenorhabditis elegans genes on the locomotive health of the animals along their lifespans. We found that knock-down of six genes affected healthspan while lifespan remained unchanged. For two of these, F26A3.4 and chn-1, knock-down resulted in an improvement of healthspan. In follow-up experiments we showed that knockdown of F26A3.4 indeed improves locomotive health and muscle structure at old age.

Automated summary

Understanding healthy aging is a challenge in biogerontology. Although many genes are known to affect lifespan, the effects on healthspan are unclear. A platform called WorMotel was used to study the effects of gene knockdown on locomotive health in Caenorhabditis elegans. Knockdown of six genes affected healthspan without altering lifespan, and knockdown of F26A3.4 and chn-1 improved healthspan. Follow-up experiments confirmed that knockdown of F26A3.4 improved locomotive health and muscle structure in old age.