Pharyngeal pumping rate does not reflect lifespan extension in C. elegans transgenerational longevity mutants

Abstract

Epigenetic modifications must be reprogrammed with each new generation. In Caenorhabditis elegans , defects in histone methylation reprogramming allow for the transgenerational acquisition of longevity. For example, mutations in the putative H3K9 demethylase JHDM-1 extend lifespan after six to ten generations. We noticed that long-lived jhdm-1 mutants appear healthier than wild-type animals from the same generation. To quantify health, we compared the common metric of pharyngeal pumping rate at specific adult ages between early-gen populations with normal lifespans and late-gen populations with long lifespans. Longevity did not affect pumping rate, but long-lived mutants stop pumping at a younger age, suggesting a possible conservation of energy to extend lifespan.

Figure 1. Lifespan extension in jhdm-1 mutants does not affect pumping rate, but long-lived populations stop pumping at a younger age.

(A, B) Representative lifespan of jhdm-1 ( ok2364 ) mutants (blue) and generation-matched wild-type animals (gray) in early-gen ( A, C, E ) and late-gen populations ( B, D, F ). Lifespan was assessed for 3-4 independent transgenerational replicates, with one representative replicate shown here. (A) In early-gen F8 populations, jhdm-1 mutants are not long-lived. (B) In late-gen F13 populations, the median lifespan of jhdm-1 mutants was 5.26% longer than generation matched wild-type *p<0.05 with a long-rank test. (C, D) Pharyngeal pumping rate of jhdm-1 mutants (blue) in both early-gen ( C ) and late-gen ( D ) populations did not differ from generation matched wild-type animals (gray). Graphs combine data from three independent transgenerational replicates. Median is shown as a black line. (E, F) Percentage of the population pumping in jhdm-1 mutants (blue) and generation-matched wild-type (gray) across generational time. Graphs combine data from two independent transgenerational replicates. Total N values are shown in white. (E) Throughout adulthood, the percentage of early-gen jhdm-1 mutants that are pumping does not differ from wild-type. (F) In populations of late-gen jhdm-1 mutants that have acquired longevity, fewer animals are pumping in middle age (Day 8 of adulthood). *p<0.05 with a Fisher’s exact test.