Dietary restriction - from intermittent fasting to cutting calories - consistently extended lifespan across all vertebrate species analysed in this study.
Rapamycin increased lifespan to the same extent as dietary restriction.
Metformin showed no clear longevity benefit although it is widely used for type 2 diabetes.
Lifespan gains were the same for males and females, and did not depend on the type of diet restriction.
The anti-aging drug Rapamycin (sirolimus) has the same life-extending effect as eating less, according to new research from the University of East Anglia and University of Glasgow.
Dietary restriction has long been considered one of the most reliable methods for increasing lifespan across species.
But if fasting for hours sounds unpleasant, science may suggest another route to achieving a longer and healthier life.
A new study published today reveals compelling evidence that Rapamycin, a compound originally developed as an immunosuppressant, offers comparable life-extending benefits in eight species of vertebrates, not including humans.
Co-lead researcher Dr Zahida Sultanova, from UEA’s School of Biological Sciences, said: “Dietary restriction - for example through intermittent fasting or reduced calorie intake - has been the gold standard for living longer. But it’s difficult for most of us to maintain long-term.
“We wanted to know if popular anti-aging drugs like Rapamycin or Metformin could offer similar effects without the need to cut calories.”
The research team looked at data from 167 studies of lifespan across eight vertebrate species including fish, mice, rats and primates – in this, the largest study of its kind.
They investigated the effect of dietary restriction on longevity - as well as that of Rapamycin and Metformin, both of which have been touted as life-extending drugs.
The team found that Rapamycin extends lifespan almost as consistently as eating less, while the Type 2 diabetes medicine, Metformin, does not.
We found that eating less still came out on top as the most consistent way to prolong life in all animals but rapamycin was close behind. Metformin, in contrast, showed no clear benefit. The life-extension effect of eating less was the same in both sexes, and it didn’t matter whether the diet plan involved eating smaller portions or intermittent fasting.
That makes rapamycin one of the most exciting leads for new anti-ageing therapies. Ageing might not be considered a disease, but it is a risk factor behind many diseases from cancer to dementia. If we slow that underlying process, the benefit will be extra years of quality life and lower healthcare bills as the world’s population grows older.
Metformin is useful, but not by itself (unless you are diabetic). If you pair Metformin (or Acarbose or SGLT2i) with Rapamycin, you get an enhancement of Rapamycin’s benefits. Metformin counteracts some of Rapamycin’s negatives making it even more potent.
However, if you are not diabetic or not taking Rapamycin, you probably shouldn’t take Metformin.
This is what I was thinking. I’m using berberine but I’m thinking of swapping to metformin on the day before, day of and 2 days after rapamycin dosing as it doesn’t interact with CYP3A4 and there is some evidence it is a beneficial combination. I’ll use berberine other days though I might end up using metformin permanently depending on how I react to it.
Metformin reduces glucose intolerance caused by rapamycin treatment in genetically heterogeneous female miceMetformin reduces glucose intolerance caused by rapamycin treatment in genetically heterogeneous female mice | Aging “In genetically heterogeneous HET3 mice, we found that chronic administration of encapsulated rapamycin by diet caused a measurable defect in glucose metabolism in both male and female mice as early as 1 month after treatment. In female mice, this defect was alleviated over time by simultaneous treatment with metformin, also by diet, such that females treated with both drugs where indistinguishable from control mice during glucose tolerance tests”
Interesting effect on weight though I’d like to see a more thorough breakdown of fat vs muscle vs bone mass: “After 9 months of treatment, eRapa males weighed significantly less than all other groups including eRapa+Met mice suggesting that metformin abolishes this effect of rapamycin. Females treated with rapamycin, either eRapa or eRapa+Met, weighed significantly less than control and Met-treated females starting at 3 months of treatment and continuing through 9 months (Figure 1). The masses of most fat depots were reduced in mice fed rapamycin at this 9 month point, as were hind-limb skeletal muscle mass in males and kidney mass reduced in female mice fed rapamycin (Supplementary Table 1). Metformin had no effect on tissue mass at this time point except for a small reduction in hind limb muscle mass in females.”
“Our main finding here is that a multi-drug approach utilizing metformin can alleviate common metabolic deficits associated with chronic rapamycin treatment as a pro-longevity therapeutic.”
For centuries, humans have searched for ways to extend life. Alchemists never found the philosopher’s stone, but scientists have consistently shown that a longer life can be attained by eating less – at least in certain lab animals. But can we find a way to live longer while still enjoying our food?
Compounds that mimic the biological effects of dieting could be the answer, and the two most popular diet-mimicking drugs are rapamycin and metformin. In a new study, my colleagues and I found that rapamycin prolongs life almost as consistently as eating less, whereas metformin does not.
Hi all – I’m considering adding Metformin (500mg twice daily with meals) to my stack and would appreciate any feedback, especially from those with experience combining it with Rapamycin and Acarbose.
Current Core Protocol:
Rapamycin: 18mg fortnightly (single dose)
Acarbose: 200mg with every meal
Metabolic background: Very mild insulin resistance (confirmed via Glucose-Insulin Tolerance Test), likely genetic
Primary Goal for Metformin:
Targeting potential anti-cancer benefits via:
Blunting post-prandial glucose spikes
Lowering overall circulating glucose
Nudging metabolism further toward ketone utilization
Relevant Context:
I’m already on a comprehensive longevity and cardiovascular protocol, including:
I’ll share that metformin did not drastically lower my post prandial glucose spikes. Replacing it with dapagliflozin made a much bigger difference, for me.
