High transcript levels of heat-shock genes are associated with shorter lifespan of Caenorhabditis elegans

Abstract

Individual lifespans of isogenic organisms, such as Caenorhabditis elegans nematodes, fruit flies, and mice, vary greatly even under identical environmental conditions. To study the molecular mechanisms responsible for such variability, we used an assay based on the measurement of post-reproductive nematode movements stimulated by a moderate electric field. This assay allows for the separation of individual nematodes based on their speed. We show that this phenotype could be used as a biomarker for aging because it is a better predictor of lifespan than chronological age. Fast nematodes have longer lifespans, fewer protein carbonyls, higher heat-shock resistance, and higher transcript levels of the daf-16 and hsf-1 genes, which code for the stress response transcription factors, than slow nematodes. High transcript levels of the genes coding for heat-shock proteins observed in slow nematodes correlate with lower heat-shock resistance, more protein carbonyls, and shorter lifespan. Taken together, our data suggests that shorter lifespan results from early-life damage accumulation that causes subsequent faster age-related deterioration.

Chaperone AMPylation modulates aggregation and toxicity of neurodegenerative disease-associated polypeptides

“…S1 C ). Ablation of hsf-1 or daf-16, two transcription factors implicated in the control of HSP transcription ( 37 , 38 ), as well as skn-1, a major transcriptional regulator implicated in the control of aging, did not reduce the beneficial effect of FIC-1(E274G) expression in Aβ worms. This result is consistent with the notion that FIC-1(E274G) acts on preexisting chaperone pools rather than by changing the overall abundance of HSF-1–, SKN-1–, or Daf-16–dependent HSPs ( SI Appendix , Fig.…”

Small heat shock proteins in ageing and age-related diseases

“…The abundance of several sHSP homologues (such as HSP-16.48, HSP-43, HSP-17 and SIP-1) increases in aged nematodes. Moreover, elevated HSP-16.2 and HSP-16.11 expression can be utilized as an efficient predictor of shorter lifespan in an electrotaxis-based assay for assessing lifespan (Manière et al 2014). Genetic inhibition of various molecular chaperones significantly shortens the organism's lifespan (Hsu et al 2003).…”

The Natural Variation in Lifespans of Single Yeast Cells Is Related to Variation in Cell Size, Ribosomal Protein, and Division Time

“…Further complexity is added by the fact that even in laboratory models, individuals that are genetically identical and that are raised under the same environmental conditions, still have highly variable lifespans showing the typical sigmoidal lifespan curve at the population level [1–5]. …”