I thought about this while reading this paper: The mTOR Signaling Pathway in Cardiac Aging
The “rapamycin memory” discussed above is not limited to cardiac aging. Transient rapamycin treatment for 3 months, initiated for ~20-21 months-old mice, is sufficient to increase life expectancy by ~40%-60% and improve several measures of healthspan in middle-aged mice. A recent study reported a long-lasting geroprotection from brief rapamycin treatment in early adulthood. This was the result of a persistent increase in intestinal autophagy in Drosophila. This “memory” was confirmed by enhanced gut barrier function and Paneth cell architecture in mice exposed to short-term RP treatment.
Too high a dose can also be risky:
In the heart, the hyperactivation of mTORC1 leads to pathological growth (cardiac hypertrophy) and cardiac dysfunction, as seen in aging and in response to pressure overload stress. Moderate suppression of mTORC1 by calorie restriction, rapamycin or some genetic models of reduced mTORC1 has been shown to ameliorate cardiac aging and pressure-overload-induced heart failure. In contrast, cardiac-specific ablation of mTORC1 leads to dilated cardiomyopathy, as it may suppress protein synthesis required for adaptive cardiac hypertrophy. The role of mTORC2 in cardiac aging is less defined. In contrast to the detrimental effect of mTORC1 activation, overexpression of the mTORC2 component in Drosophila is cardioprotective; however, the role of mTORC2 in mammals remains to be elucidated.
What’s your rapa dosing schedule @John_Hemming?