Age-dependent changes in mobility and separation of the nematode Caenorhabditis elegans

Hosono, Ryuji; Sato, Yoshiko; Aizawa, Shin-Ichi; Mitsui, Youji

doi:10.1016/0531-5565(80)90032-7

Cited by 96 publications

(74 citation statements)

References 6 publications

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“…Here, we use a method similar to that of Hosono, Sato, Aizawa, and Mitsui (1980) and Herndon et al. (2002), which categorizes movement into one of three classes, A, B, and C. All animals begin adult life with Class A movement, a marker of a vigorous, youthful state with minimal functional decline.…”

Section: Resultsmentioning

confidence: 99%

“…Study of the age‐related loss of movement has been well documented in C. elegans and has been used as a marker of healthspan (Bolanowski et al., 1981; Duhon & Johnson, 1995; Glenn et al., 2004; Herndon et al., 2002; Honda & Honda, 2002; Hosono et al., 1980; Hsu, Feng, Hsieh, & Xu, 2009; Huang et al., 2004; Johnson, 1987; Shook, Brooks, & Johnson, 1996). Mechanisms of movement decline include structural and molecular changes resembling human sarcopenia (decrease in size and number of muscle cells, fraying of fibers, and loss of sarcomere integrity, Herndon et al., 2002), reduced neuronal signaling (Liu et al., 2013), and changes in exploratory behaviors (Hahm et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…Both worm movement and pharyngeal pumping rate have been shown to decrease with age (Hosono et al ., 1980), and so any delay in this decline would indicate a slower rate of aging. All the treated worms, except those treated with geldanamycin, showed no change in the decline of movement rate (Fig S4–S12).…”

Section: Resultsmentioning

confidence: 99%

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

et al. 2015

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SummaryCaloric restriction (CR), a reduction in calorie intake without malnutrition, retards aging in several animal models from worms to mammals. Developing CR mimetics, compounds that reproduce the longevity benefits of CR without its side effects, is of widespread interest. Here, we employed the Connectivity Map to identify drugs with overlapping gene expression profiles with CR. Eleven statistically significant compounds were predicted as CR mimetics using this bioinformatics approach. We then tested rapamycin, allantoin, trichostatin A, LY‐294002 and geldanamycin in Caenorhabditis elegans. An increase in lifespan and healthspan was observed for all drugs except geldanamycin when fed to wild‐type worms, but no lifespan effects were observed in eat‐2 mutant worms, a genetic model of CR, suggesting that life‐extending effects may be acting via CR‐related mechanisms. We also treated daf‐16 worms with rapamycin, allantoin or trichostatin A, and a lifespan extension was observed, suggesting that these drugs act via DAF‐16‐independent mechanisms, as would be expected from CR mimetics. Supporting this idea, an analysis of predictive targets of the drugs extending lifespan indicates various genes within CR and longevity networks. We also assessed the transcriptional profile of worms treated with either rapamycin or allantoin and found that both drugs use several specific pathways that do not overlap, indicating different modes of action for each compound. The current work validates the capabilities of this bioinformatic drug repositioning method in the context of longevity and reveals new putative CR mimetics that warrant further studies.

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“…Locomotion behavior represents one of the most prominent behaviors in C. elegans [4]. It is known that old worms develop motor deficits and are less active than young worms [5,9,13,14,16,18]. Indeed, the expression of motor activity has been used as a common standard in lifespan analysis to score whether a worm is alive [20].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the expression of motor activity has been used as a common standard in lifespan analysis to score whether a worm is alive [20]. Previous studies have attempted to correlate the behavioral states of worm locomotion with the biological age of the animal, and some qualitative or semi-quantitative parameters have been proposed to predict lifespan at the late or mid-to-late rather than early stage of aging [13,14,18]. For example, there appears to be a correlation between the lifespan of a worm and the number of days during which it can maintain active movement [14].…”

Section: Introductionmentioning

confidence: 99%

Identification by machine vision of the rate of motor activity decline as a lifespan predictor in C. elegans

Hsu

Feng

Hsieh

et al. 2009

Neurobiology of Aging

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One challenge in aging research concerns identifying physiological parameters or biomarkers that can reflect the physical health of an animal and predict its lifespan. In C. elegans, a model organism widely used in aging research, motor deficits develop in old worms. Here we employed machine vision to quantify worm locomotion behavior throughout lifespan. We confirm that aging worms undergo a progressive decline in motor activity, beginning in early life. Importantly, the rate of motor activity decline rather than the absolute motor activity in the early-to-mid life of individual worms in an isogenic population inversely correlates with their lifespan, and thus may serve as a lifespan predictor. Long-lived mutant strains with deficits in insulin/IGF-1 signaling or food intake display a reduction in the rate of motor activity decline, suggesting that this parameter might also be used for across-strain comparison of healthspan. Our work identifies an endogenous physiological parameter for lifespan prediction and healthspan comparison.

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Age-dependent changes in mobility and separation of the nematode Caenorhabditis elegans

Cited by 96 publications

References 6 publications

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

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

A network pharmacology approach reveals new candidate caloric restriction mimetics in C. elegans

Identification by machine vision of the rate of motor activity decline as a lifespan predictor in C. elegans

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