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. 2015 Nov 20:6:8919.
doi: 10.1038/ncomms9919.

C. elegans maximum velocity correlates with healthspan and is maintained in worms with an insulin receptor mutation

Jeong-Hoon Hahm  1 , Sunhee Kim  1 , Race DiLoreto  2 , Cheng Shi  2 , Seung-Jae V Lee  3 , Coleen T Murphy  2 , Hong Gil Nam  1   4
Affiliations

C. elegans maximum velocity correlates with healthspan and is maintained in worms with an insulin receptor mutation

Jeong-Hoon Hahm et al. Nat Commun. .

Abstract

Ageing is marked by physical decline. Caenorhabditis elegans is a valuable model for identifying genetic regulatory mechanisms of ageing and longevity. Here we report a simple method to assess C. elegans' maximum physical ability based on the worms' maximum movement velocity. We show maximum velocity declines with age, correlates well with longevity, accurately reports movement ability and, if measured in mid-adulthood, is predictive of maximal lifespan. Contrary to recent findings, we observe that maximum velocity of worm with mutations in daf-2(e1370) insulin/IGF-1 signalling scales with lifespan. Because of increased odorant receptor expression, daf-2(e1370) mutants prefer food over exploration, causing previous on-food motility assays to underestimate movement ability and, thus, worm health. Finally, a disease-burden analysis of published data reveals that the daf-2(e1370) mutation improves quality of life, and therefore combines lifespan extension with various signs of an increased healthspan.

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Figures

Figure 1
Figure 1. MV is correlated with longevity.
(a) Age-dependent changes in the MV of 52 individual wild-type worms. Black dots represent the average value at each age. (b,c) Correlation between MV and lifespan (b) and correlation between mean velocity and lifespan (c) of individual worms. The MVs and mean velocities of individual worms were measured at day 9 of adulthood and their lifespans were measured thereafter. r2, coefficient of determination. n=173. (d) Survival curves of the low-MV (n=89) and high-MV (n=84) group worms. The groups were divided at day 9 of adulthood (grey dotted line) and the survivorship of worms in each group was measured thereafter. (e) Correlation of MV with mitochondrial morphology at day 9 of adulthood. Scores of mitochondrial morphology of low-MV and high-MV groups were 1.3±0.5 and 2.5±0.5, respectively (n=27). The bottom and top of the box and whiskers are the first and third quartiles, and the band inside the box is the average. Significance was determined using a two-tailed, unpaired t-test. ****P<0.0001.
Figure 2
Figure 2. Correlation of MV with lifespan in daf-2 mutants.
(a) Age-associated change of survivorship in N2 (wild type) (n=52), daf-2(e1370) (n=32) and daf-16(mu86) (n=42) worms. (b,c) Age-associated change of MVs in daf-2 (b) and daf-16 mutant worms (c). (d) Age-associated change of average MVs in N2 (n=52), daf-2 (n=32) and daf-16 (n=42) mutant worms. Error bars represent s.d. (e) A cumulative difference in physical performance in N2 and daf-16 and daf-2 mutant worms as indicated by area under curves in d. The relative values of area under curves are 1.0±0.2, 0.9±0.2 and 2.4±0.4 for N2, daf-16 and daf-2 worms, respectively. (f) Comparison of healthspan and gerospan in N2, daf-16 and daf-2 worms. Healthspan was defined as ‘the period during which the worm showed >50% maximal functional capacity of wild type'. Gerospan was defined as ‘the period during which the worm showed <50% maximal functional capacity of wild type'. (g) The healthspan-to-gerospan ratio normalized to their maximal lifespan in N2, daf-16 and daf-2 worms.
Figure 3
Figure 3. Motility on bacteria measures food preference rather than ability to move.
(a) Two sets of primers (#1 and #2) were used to measure the expression of odr-10 by qRT-PCR in N2 and daf-2 mutants. For each primer set, odr-10 expression in wild type was normalized to 1. odr-10 expression in daf-2 mutants increased by 15.2±0.2-fold and 19.4±3.1-fold, respectively. (b) Reduction of odr-10 levels by RNAi increased daf-2 motility on bacteria significantly. daf-2 on OP50: 0.04±0.03 mm s−1; daf-2; odr-10(RNAi): 0.11±0.01 mm s−1 (c) wild-type worms' motility on bacteria was not significantly affected by reduction of odr-10: N2 worms on OP50: 0.17±0.03 mm s−1; N2 on odr-10(RNAi): 0.14±0.03 mm s−1. n=3, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001; unpaired t-test.
Figure 4
Figure 4. Quality-adjusted health metrics.
daf-2 mutants are healthier than wild type. (a) Quality-adjusted lifespan curves for the health metrics observed by Bansal et al., with each metric normalized to the maximum value of the wild type. (b) The quality-adjusted lifespan curve is the survival rate multiplied by the normalized health measurement. (c) Visualizing the cumulative area under the quality-adjusted lifespan curve at each time point shows that daf-2 mutants have higher lifespan quality over most measured health metrics. (d) Analysis of additional healthspan data measured by Huang et al. shows a similar increase in total lifespan quality of daf-2 mutants over wild type.
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References

    1. Kenyon C. J. The genetics of ageing. Nature 464, 504–512 (2010). - PubMed
    1. Bansal A., Zhu L. H. J., Yen K. & Tissenbaum H. A. Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants. Proc. Natl Acad. Sci. USA 112, E277–E286 (2015). - PMC - PubMed
    1. Kenyon C., Chang J., Gensch E., Rudner A. & Tabtiang R. A C. elegans mutant that lives twice as long as wild type. Nature 366, 461–464 (1993). - PubMed
    1. Ogg S. et al.. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C-elegans. Nature 389, 994–999 (1997). - PubMed
    1. Lin K., Hsin H., Libina N. & Kenyon C. Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat. Genet. 28, 139–145 (2001). - PubMed

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