The Anti-Rapamycin: Increasing mTORC1 Accelerates aging and inflammation

[RapAdmin]

This seems like a very interesting bit of new research that further validates Rapamycin’s benefits…

Full details below:

A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan

The mechanistic target of rapamycin complex 1 controls cellular anabolism in response to growth factor signaling and to nutrient sufficiency signaled through the Rag GTPases. Inhibition of mTOR reproducibly extends longevity across eukaryotes. Here we report that mice that endogenously express active mutant variants of RagC exhibit multiple features of parenchymal damage that include senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive features of inflammaging and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, we show that myeloid cells are abnormally activated by signals emanating from dysfunctional RagC-mutant parenchyma, causing neutrophil extravasation that inflicts additional inflammatory damage. Therapeutic suppression of myeloid inflammation in aged RagC-mutant mice attenuates parenchymal damage and extends survival. Together, our findings link mildly increased nutrient signaling to limited lifespan in mammals, and support a two-component process of parenchymal damage and myeloid inflammation that together precipitate a time-dependent organ deterioration that limits longevity.

Open Access Paper:

https://www.nature.com/articles/s43587-024-00635-x

[DeStrider]

Excellent article. It’s good to have more evidence that what we’re doing is correct.

[RapAdmin]

Source: x.com

Her Reference:

Reducing the metabolic burden of rRNA synthesis promotes healthy longevity in Caenorhabditis elegans

https://www.nature.com/articles/s41467-024-46037-w

[SilentWatcher]

@RapAdmin

A mild increase in nutrient signaling to mTORC1 in mice leads to parenchymal damage, myeloid inflammation and shortened lifespan

Hmmm… this confirms the fact that chronic “muscle building” = chronic mTORC1 activation (high protein, +creatine, +BCAAs, +HMB, +…) is detrimental to longevity.

[Virilius]

The mice in the study were not trained.

[nikney]

@RapAdmin

Here we report that mice endogenously expressing active mutant variants of RagC display multiple features of parenchymal damage, including senescence, expression of inflammatory molecules, increased myeloid inflammation with extensive inflammatory features, and a ~30% reduction in lifespan. Through bone marrow transplantation experiments, myeloid cells were detected by signals emanating from dysfunctional RagC-mutant parenchyma.

mtorc1 is an almost unnecessary signaling pathway that sends the organism to death after the organism completes its development, which is around 35 years of age in humans.

[RapAdmin]

Researchers find that excess nutrients in cells trigger inflammation and organ dysfunction, accelerating aging. Their study suggests that interventions in inflammation might improve lifespan.

The accelerated aging of our population underscores the urgency to understand the molecular changes occurring in the body over time. The mTOR protein complex plays a critical role in many body functions, particularly in metabolism. A new study by Spanish National Cancer Research Center (CNIO) researchers shows that even slight increases in mTOR activity can induce premature aging in animal models, reducing their lifespan by up to 20%.

This study, published in Nature Aging, provides insights into why diseases associated with aging worsen in individuals with a high body mass index, an indicator of obesity and inflammation. It also explains why calorie restriction, known for extending lifespan in animals, promotes healthy aging by activating specific genes that interact with mTOR.

Additionally, the study introduces a new research tool designed “to study the relationship between nutrient increase and the ageing of different organs,” according to lead author Alejo Efeyan, who heads the Metabolism and Cell Signalling Group at the National Cancer Research Centre (CNIO).

Cutting-Edge Study Reveals a Link Between Obesity, Inflammation, and Aging

[RapAdmin]

mTOR links nutrients, inflammaging and lifespan

(commentary on the research paper at the top of this thread)

Source: mTOR links nutrients, inflammaging and lifespan | Nature Aging