Longevity interventions temporally scale healthspan in Caenorhabditis elegans

Abstract

Longer lived individuals, such as centenarians or longevity mutants of model organisms, have later onsets and lower incidence rates of late-life morbidities or disabilities than the average population. However, whether increased lifespan is caused by a compression of the portion of life spent in a state of morbidity, i.e., “sickspan,” is highly debated. It is unclear which health matrices are representative for measuring healthspan (time spent in good health); however, muscular performance is generally a good indicator for the health status in humans and a predictor for their mortality, regardless of the underlying cause. Here, we developed a novel microfluidic device that employs acoustophoretic force fields to quantify the maximum muscle strength and dynamic power in aging C. elegans populations. We found that longevity mutants have a delayed onset and lower declining rates in maximum muscle strength compared to wild type. Reconciling previous conflicting reports, we confirmed that certain longevity mutants exhibited a mild increase in relative sickspan measured by voluntary movement matrices, which is not the case when using our acoustophoretic force measurements, swim endurance, or other approaches. Using six different biomarkers for healthspan, we observed a time-dependent onset of morbidity, starting with a loss of stress resilience, a decline in dynamic power, and a decline in structural integrity, culminating finally in inactivity (lethargy) and a loss of mobility. We observed that a subset of aging biomarkers correlate with each other and maybe functionally interconnected. Surprisingly, we did not observe a compression of sickspan in longevity mutants but instead observed a temporal scaling of healthspan with diminishing returns for extreme lifespan extensions. Given the conservation of these longevity interventions, this raises the question of whether the healthspan of mammalian longevity interventions is temporally scaled as well.