🔬TODAY’S BREAKTHROUGH
A new study reveals that the oncology drug trametinib, by inhibiting MEK1, can activate chaperone-mediated autophagy (CMA), clearing aging-related metabolic enzymes and extending lifespan in animal models.
The Discovery:
In aged model organisms, low-dose trametinib treatment significantly enhanced lifespan and healthspan. It promoted the degradation of lipogenesis enzymes through CMA, reduced hepatic fat accumulation, and improved metabolic profiles.
The Science:
MEK1 (mitogen‑activated protein kinase kinase 1) is part of the MAPK pathway, linked to cell growth and metabolism
Trametinib inhibits MEK1, triggering activation of CMA, a targeted autophagy route where proteins are delivered to lysosomes for breakdown
CMA selectively degraded key enzymes in de novo lipogenesis, such as FASN and ACC1, reducing hepatic lipid content
Treated animals showed lower liver fat, improved glucose metabolism, and better lipid homeostasis
Lifespan extension occurred without general autophagy upregulation, highlighting CMA specificity
Suggests a clear mechanism: metabolic enzyme clearance via CMA as a pathway to longevity
Your Action:
Support metabolic and autophagic health with:
Intermittent fasting or time-restricted eating, which naturally boost CMA and autophagy.
Physical activity, particularly moderate aerobic exercise, linked to increased lysosomal function and autophagy.
Coffee or tea polyphenols, which may assist CMA induction.
Consider periodic metabolic health screening: lipid panels, liver enzymes, and body composition tracking.
Bottom Line:
Trametinib extends lifespan in animals by activating CMA to clear aging-related lipogenic enzymes, revealing a targeted metabolic rejuvenation strategy.
Source:
The lifespan-extending MEK1 inhibitor trametinib promotes regulation of de novo lipogenesis enzymes by chaperone-mediated autophagy, Frontiers in Aging, June 25, 2025
https://www.frontiersin.org/articles/10.3389/fragi.2025.1621808/full
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Disclaimer:
This newsletter is for informational purposes only and does not substitute professional medical advice. Always consult with a healthcare provider before making any changes to your health regimen.