After watching Dr. Mannicks interview recently, she mentioned a shift in mTOR regulation that occurs as we get older. I believe she said that normally, when fasting in our youth, mTOR is inhibited, but as we age, fasting does not inhibit mTOR as well. If we are trying to mimic our youthful mTOR regulation that usually is turned off while fasting at night, then should we take our doses of Rapamycin at night?
I know many have shared their experience of a higher HR and a lower HRV the day of dosing. Also, many have the desire to dose in the morning with fatty food and or grapefruit to maximize absorption / dosing.
Just a thought for discussion. Maybe an ideal longevity rapalog would have a very short half life and be taken at night to mimic youthful mTOR regulations?
It is an interesting question… historically perhaps there has been greater levels of mTOR inhibition and autophagy during the night since we are in a fasted state. Though, another thought is that historically, in evolutionary terms, most autophagy has probably happened during times of food deprivation (the common cycle of feast or famine in hunter/gatherer type societies)… especially given that I’ve heard that it typically takes 48 hours to 36 hours+ of fasting to truly get into a good mTOR inhibition state, and upregulated autophagy…
So, my thoughts are yes, in today’s modern society nights are the most common form of “fasting” that most people experience in their lives. And taking rapamycin in the evening seems like it might duplicate that effect in greater ages… but perhaps countering that is that many of us seem to suffer in our sleep when we take rapamycin in the evening, so that might counter the benefits…
And, if you look at the longer span of history, it seems likely that longer periods of “fasting” (food deprivation) would have been much, much more common, lasting days or weeks or longer, so perhaps that is the condition we may want to try to replicate (via high doses of rapamycin for several days/weeks or months)… and perhaps how our bodies have evolved to best reap the benefits of autophagy?
Great points! I was extrapolating what I think she meant on Younger mTOR modulation vs. Older mTOR modulation in modern day and just assumed the fasting she was referring to was fasting during sleep since most people do not fast unless religious or dieting.
The current evidence suggests that anywhere between 18 hours (as evidenced by the eTFR study) to four days will trigger autophagy.[5-7] However, only a handful of studies measuring fasting and autophagy exist in humans. As mentioned above, intermittent fasting, calorie restriction, and exercise are all ways to boost autophagy that don’t involve fasting for several days.