Movement decline across lifespan of Caenorhabditis elegans mutants in the insulin/insulin‐like signaling pathway

Abstract

SummaryResearch in aging biology has identified several pathways that are molecularly conserved across species that extend lifespan when mutated. The insulin/insulin‐like signaling (IIS) pathway is one of the most widely studied of these. It has been assumed that extending lifespan also extends healthspan (the period of life with minimal functional loss). However, data supporting this assumption conflict and recent evidence suggest that life extension may, in and of itself, extend the frail period. In this study, we use Caenorhabditis elegans to further probe the link between lifespan and healthspan. Using movement decline as a measure of health, we assessed healthspan across the entire lifespan in nine IIS pathway mutants. In one series of experiments, we studied healthspan in mass cultures, and in another series, we studied individuals longitudinally. We found that long‐lived mutants display prolonged mid‐life movement and do not prolong the frailty period. Lastly, we observed that early‐adulthood movement was not predictive of late‐life movement or survival, within identical phenotypes. Overall, these observations show that extending lifespan does not prolong the period of frailty. Both genotype and a stochastic component modulate aging, and movement late in life is more variable than early‐life movement.

Secoisolariciresinol Diglucoside Delays the Progression of Aging-Related Diseases and Extends the Lifespan ofCaenorhabditis elegansvia DAF-16 and HSF-1

“…We found worm did not avoid SDG (Figures 1(d) and S1 ). The body movement of C. elegans decreases with aging [ 25 ]. To investigate whether SDG could delay the age-related decline of phenotypes, the body movement of worms was monitored and analyzed.…”

Longitudinal assessment of health-span and pre-death morbidity in wild type Drosophila

“…Disability is divided into mid- and late-life disability associated with reduced spontaneous movements, followed by a period of frailty when spontaneous activity ceases [7]. In insulin/insulin-like signaling (IIS) pathway mutants lifespan and mid-life disability are extended, but the frailty period remains unaltered [8]. Insulin signaling is also a major factor of aging in mammals [9,10] and in fruit flies [11], thus indicating that some mechanisms of aging are highly conserved.…”

Optimized criteria for locomotion-based healthspan evaluation in C. elegans using the WorMotel system

“…The nematode C. elegans is a well-established model for aging with the advantages of a short lifespan and ease of cultivation. Work in this model indicates that a longer lifespan does not always correlate with proportional increases in healthy life [6][7][8][9], reaffirming the notion that understanding how organisms can age healthily is important.…”