Amazing stuff! When can I go into hibernation to wake up perhaps in the next century? 😴
"New research has identified specific regions of DNA that regulate hibernation by tweaking metabolism. The findings could offer pathways to new treatments for metabolic disorders like type 2 diabetes in humans.
When hibernating animals wake, they reverse dangerous health changes similar to those seen in type 2 diabetes, muscle atrophy, Alzheimer’s disease and stroke. ...
Ferris is co-author of 2 new studies which pinpointed that DNA regions near a gene cluster called the “fat mass and obesity (FTO) locus” play a crucial role in the ability to hibernate. While the FTO locus also appears in humans, hibernating animals use it in a different, and potentially more advantageous way. ...
The hibernator-specific DNA regions (located close to the FTO locus) weren’t genes but DNA sequences called “cis–regulatory elements” (CREs) which contact nearby genes to either turn up or down their expression, ... The researchers found the CREs regulated the activity of neighbouring genes, including those involved in metabolism. ..."
From the editor's summary and abstract:
"Editor’s summary
Metabolic regulation is fundamental to many aspects of health and disease. Two companion papers investigated the genetic bases of mammalian metabolic control by studying the genetic changes associated with hibernation. Ferris et al. performed a comparative analysis of gene expression and chromatin dynamics in a non hibernating mouse and a hibernating squirrel, focusing on the hypothalamus, a brain area involved in metabolic adaptations. They identified a convergent set of cis-regulatory elements (CREs) associated with the adoption of a hibernating lifestyle. Steinwand et al. performed targeted deletion of some of these CREs, determining how these specific alterations translated into distinct metabolic and behavioral phenotypes. These studies suggest that CREs might also play a role in regulating human metabolism. ...
Abstract
Cis-regulatory elements (CREs) drive phenotypic diversity, yet how CREs are causally linked to function remains largely unclear.
Our study elucidates functions for conserved cis elements associated with the evolution of mammalian hibernation and metabolic flexibility.
Genomic analyses revealed topologically associated domains (TADs) enriched for convergent changes in hibernators, including the Fat Mass & Obesity (Fto) locus. In this TAD, we uncovered genetic circuits for metabolic responses and hibernation-linked cis elements forming regulatory contacts with neighboring genes.
Deletions of individual cis elements in mice differentially altered Fto, Irx3, and Irx5 expression, reshaping downstream gene expression programs and affecting metabolism, torpor, obesogenesis, and foraging in distinct ways.
Our findings show how convergent evolution in hibernators pinpoints functional genetic mechanisms of metabolic control, with multiple effects encoded in single CREs."
Hibernator “Superpowers” May Lie Hidden in Human DNA (original news release)
Conserved noncoding cis elements associated with hibernation modulate metabolic and behavioral adaptations in mice (no public access)
Conserved Noncoding Cis-Elements Associated with Hibernation Modulate Metabolic and Behavioral Adaptations in Mice (preprint, open access)
Fig. 1 Convergent genomic changes in hibernators identify Fto-Irx TAD cis-elements for functional analysis in knockout mice.
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