Amazing stuff!
"A new study of C. elegans traces the origin of this variation [in individual lifespans] to changes in the messenger RNA (mRNA) content in germline cells (sperm and egg cells) and somatic cells (the rest of the body). ...
The magnitude and speed of this decoupling process is influenced by a group of at least 40 genes. The genes are involved in a wide range of functions within the body, from metabolism to the neuroendocrine system.
The study found the balance of the amount of mRNA in germline and somatic cells becomes disrupted, or ‘decouples’, over time in the worms. This causes ageing to run faster in some individuals than others.
The researchers found that knocking down some of the genes (stopping their transcription into mRNA) extended a worm’s lifespan, while knocking down others shortened it. ..."
From the highlights and abstract:
"Highlights
• An atlas of 2,700 individual C. elegans transcriptomes quantifies heterogeneity in aging
• A perturbation screen identifies intrinsic drivers of this heterogeneity
• Heterogeneity in aging is driven by pleiotropic genes expressed in diverse cell types
• Suppressing intrinsic sources of heterogeneity reduces variation in health and lifespan
Summary
In aging, physiologic networks decline in function at rates that differ between individuals, producing a wide distribution of lifespan. Though 70% of human lifespan variance remains unexplained by heritable factors, little is known about the intrinsic sources of physiologic heterogeneity in aging. To understand how complex physiologic networks generate lifespan variation, new methods are needed.
Here, we present Asynch-seq, an approach that uses gene-expression heterogeneity within isogenic populations to study the processes generating lifespan variation. By collecting thousands of single-individual transcriptomes, we capture the Caenorhabditis elegans “pan-transcriptome”—a highly resolved atlas of non-genetic variation. We use our atlas to guide a large-scale perturbation screen that identifies the decoupling of total mRNA content between germline and soma as the largest source of physiologic heterogeneity in aging, driven by pleiotropic genes whose knockdown dramatically reduces lifespan variance. Our work demonstrates how systematic mapping of physiologic heterogeneity can be applied to reduce inter-individual disparities in aging."
Systematic mapping of organism-scale gene-regulatory networks in aging using population asynchrony (no public access)
Graphical abstract:
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