#1

https://scitechdaily.com/scientists-discover-mortality-timer-inside-our-cells/

So calorie restriction… fasting… keeps the nucleus small and functioning for healthy age extention. Seems rapamycin is doing the same in cleaning and maintaining a cell’s health.

Reference:

“A mortality timer based on nucleolar size triggers nucleolar integrity loss and catastrophic genomic instability”
by J. Ignacio Gutierrez, and Jessica K. Tyler, 25 November 2024, Nature Aging .
DOI: 10.1038/s43587-024-00754-5

Paywalled Paper:

Genome instability is a hallmark of aging, with the highly repetitive ribosomal DNA (rDNA) within the nucleolus being particularly prone to genome instability. Nucleolar enlargement accompanies aging in organisms ranging from yeast to mammals, and treatment with many antiaging interventions results in small nucleoli. Here, we report that an engineered system to reduce nucleolar size robustly extends budding yeast replicative lifespan in a manner independent of protein synthesis rate or rDNA silencing. Instead, when nucleoli expand beyond a size threshold, their biophysical properties change, allowing entry of proteins normally excluded from the nucleolus, including the homologous recombinational repair protein Rad52. This triggers rDNA instability due to aberrant recombination, catastrophic genome instability and imminent death. These results establish that nucleolar expansion is sufficient to drive aging. Moreover, nucleolar expansion beyond a specific size threshold is a mortality timer, as the accompanying disruption of the nucleolar condensate boundary results in catastrophic genome instability that ends replicative lifespan.

https://www.nature.com/articles/s43587-024-00754-5

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#2

just curious: does Rapa decrease size of nucleoli or at least prevent increasing size?
If not then the hypothesis in this article would possibly be incorrect.

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#3

Rapamycin causes cells to go into starvation mode and start cleaning up… like fasting.

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