Metabolic slowdown as the proximal cause of ageing and death PaperPlayer biorxiv systems biology
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- Life Sciences
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.08.01.551537v1?rss=1
Authors: Wordsworth, J., Yde Nielsen, P., Fielder, E., Chandrasegaran, S., Shanley, D.
Abstract:
Ageing results from the gradual loss of homeostasis, and there are currently many hypotheses for the underlying initial causes, such as molecular damage accumulation. However, few if any theories directly connect comprehensive, underlying biological mechanisms to specific age-related diseases. We recently demonstrated how a specific maintenance system impeding overactivity disorders such as cancer might undergo positive selection while still resulting in a gradual homeostatic shift toward slower metabolism. Here we connect this metabolic slowdown, via a series of unavoidable homeostatic shifts, to the hallmarks of ageing, including mitochondrial dysfunction, insulin resistance (IR), weight gain, basal inflammation, and age-related diseases such as atherosclerosis. We constructed the fuel and energy model (FEM) based on these shifts and found that ageing via metabolic slowdown could explain not only the effects of anti-ageing interventions such as rapamycin and calorie restriction, but many of the paradoxes of ageing that currently defy alternative theories.
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Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.08.01.551537v1?rss=1
Authors: Wordsworth, J., Yde Nielsen, P., Fielder, E., Chandrasegaran, S., Shanley, D.
Abstract:
Ageing results from the gradual loss of homeostasis, and there are currently many hypotheses for the underlying initial causes, such as molecular damage accumulation. However, few if any theories directly connect comprehensive, underlying biological mechanisms to specific age-related diseases. We recently demonstrated how a specific maintenance system impeding overactivity disorders such as cancer might undergo positive selection while still resulting in a gradual homeostatic shift toward slower metabolism. Here we connect this metabolic slowdown, via a series of unavoidable homeostatic shifts, to the hallmarks of ageing, including mitochondrial dysfunction, insulin resistance (IR), weight gain, basal inflammation, and age-related diseases such as atherosclerosis. We constructed the fuel and energy model (FEM) based on these shifts and found that ageing via metabolic slowdown could explain not only the effects of anti-ageing interventions such as rapamycin and calorie restriction, but many of the paradoxes of ageing that currently defy alternative theories.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC