ELO-6 expression predicts longevity in isogenic populations of Caenorhabditis elegans

Abstract

Variations of individual lifespans within genetically identical populations in homogenous environments are remarkable, with the cause largely unknown. Gene expression changes with age, and the transcriptome changes correlate with chronological aging. Here, we show that in Caenorhabditis elegans, the expression dynamic of the fatty acid elongase ELO-6 during aging predicts individual longevity in isogenic populations. The expression of elo-6 is reduced with age. From adult day 5, ELO-6 expression level exhibits variation between individuals, and the expression level is positively correlated with adult lifespan and health span. Interventions that prolong longevity enhance the expression stability of ELO-6 during aging from adult day 4 to adult day 8, indicating ELO-6 is also a populational lifespan predictor. We performed transcriptome analysis in short-lived and long-lived isogenic worms and identified differentially expressed genes, which are enriched for PQM-1 binding sites. Decreasing pqm-1 expression in young adults improved the homogeneity of ELO-6 levels between individuals and enhanced health span. Furthermore, we found reducing the expression of genes that are highly expressed in short-lived individuals, including PQM-1 target genes, enhanced ELO-6 expression stability with age and extended lifespan. Thus, our study identified ELO-6 as a predictor of individual and populational lifespan and revealed the role of pqm-1 in restricting health span and possibly causing individual lifespan variation.