Global, cell non-autonomous gene regulation drives individual lifespan among isogenic c. Elegans

Holly E. Kinser, Matthew C. Mosley, Isaac B. Plutzer, Zachary Pincus

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Across species, lifespan is highly variable among individuals within a population. Even genetically identical Caenorhabditis elegans reared in homogeneous environments are as variable in lifespan as outbred human populations. We hypothesized that persistent inter-individual differences in expression of key regulatory genes drives this lifespan variability. As a test, we examined the relationship between future lifespan and the expression of 22 microRNA promoter:: GFP constructs. Surprisingly, expression of nearly half of these reporters, well before death, could effectively predict lifespan. This indicates that prospectively long-vs. short-lived individuals have highly divergent patterns of transgene expression and transcriptional regulation. The gene-regulatory processes reported on by two of the most lifespan-predictive transgenes do not require DAF-16, the FOXO transcription factor that is a principal effector of insulin/insulin-like growth factor (IGF-1) signaling. Last, we demonstrate a hierarchy of redundancy in lifespan-predictive ability among three transgenes expressed in distinct tissues, suggesting that they collectively report on an organism-wide, cell non-autonomous process that acts to set each individual’s lifespan.

Original languageEnglish
Article numbere65026
Pages (from-to)1-27
Number of pages27
JournaleLife
Volume10
DOIs
StatePublished - Feb 2021

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