Assessing Health Span in Caenorhabditis elegans: Lessons From Short-Lived Mutants

Abstract

Genetic changes resulting in increased life span are often positively associated with enhanced stress resistance and somatic maintenance. A recent study found that certain long-lived Caenorhabditis elegans mutants spent a decreased proportion of total life in a healthy state compared with controls, raising concerns about how the relationship between health and longevity is assessed. We evaluated seven markers of health and two health-span models for their suitability in assessing age-associated health in invertebrates using C elegans strains not expected to outperform wild-type animals. Additionally, we used an empirical method to determine the transition point into failing health based on the greatest rate of change with age for each marker. As expected, animals with mutations causing sickness or accelerated aging had reduced health span when compared chronologically to wild-type animals. Physiological health span, the proportion of total life spent healthy, was reduced for locomotion markers in chronically ill mutants, but, surprisingly, was extended for thermotolerance. In contrast, all short-lived mutants had reduced "quality-of-life" in another model recently employed for assessing invertebrate health. Results suggest that the interpretation of physiological health span is not straightforward, possibly because it factors out time and thus does not account for the added cost of extrinsic forces on longer-lived strains.

HeALTH: An Automated Platform for Long-term Longitudinal Studies of Whole Organisms under Precise Environmental Control

“…Similar to previous studies, across all genotypes there appears to be a consistent initial period of frequent 'high activity' movement, followed by a period of sporadic 'low activity' movement until the individual's death [12][13][14]16]. Bouts of consistent movement suggest an initial period of good health for the worm, which may indicate a lack of sarcopenia or cognitive decline.…”

“…Existing methods of studying lifespan and the period of healthy living, or 'healthspan', in C. elegans are limited and lack the ability to provide precise environmental control. Although traditional lifespan and healthspan assays have uncovered important insights into the aging process, they require large amounts of manual labor, making it difficult to scale for different genotypes or environmental conditions [11][12][13][14]. Recent high-throughput methods have been developed for scoring longevity or observing behavior over time [15][16][17][18]; however, they also lack precise control in regulating the organism's immediate environment.…”

The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis inCaenorhabditis elegans

“…2C). Thus, while nsun-1 knockdown does not extend lifespan, it improves the healthspan parameters thermotolerance and locomotion (Bansal et al, 2015; Rollins et al, 2017).…”

Genome-wide analysis reveals distinct genetic mechanisms of diet-dependent lifespan and healthspan inD. melanogaster

“…Recent studies in humans have investigated the period at the tail end of life and how it correlates with mortality, and results have demonstrated that although disability generally increases as individuals approach death (38), the rate and severity of decline varies by case and individual (39). Studies in worms (40–43) and mice (36, 44) in select genetic backgrounds demonstrate that lifespan extension is not necessarily accompanied by an increase in healthspan. Thus these studies pose the question whether lifespan and healthspan are indeed determined by the same genetic mechanisms.…”