Global, cell non-autonomous gene regulation drives individual lifespan among isogenic <i>C. elegans</i>.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33522488.
- Also identified by DOI 10.7554/eLife.65026 and PMC identifier 7864635.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Across species, lifespan is highly variable among individuals within a population. Even genetically identical <i>Caenorhabditis elegans</i> 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.
Medical subject headings
- Caenorhabditis elegans
- Gene Expression Regulation
- Longevity
- MicroRNAs