From rapalogs to anti-aging formula

bird catching an earthworm

Abstract

Inhibitors of mTOR, including clinically available rapalogs such as rapamycin (Sirolimus) and Everolimus, are gerosuppressants, which suppress cellular senescence. Rapamycin slows aging and extends life span in a variety of species from worm to mammals. Rapalogs can prevent age-related diseases, including cancer, atherosclerosis, obesity, neurodegeneration and retinopathy and potentially rejuvenate stem cells, immunity and metabolism.

[In this paper] I further suggest how rapamycin can be combined with metformin, inhibitors of angiotensin II signaling (Losartan, Lisinopril), statins (simvastatin, atorvastatin), propranolol, aspirin and a PDE5 inhibitor. Rational combinations of these drugs with physical exercise and an anti-aging diet (Koschei formula) can maximize their anti-aging effects and decrease side effects.

SOURCE: Oncotarget

Fasting + rapamycin

Monstera plant with large droopy leaves

Abstract

Rapamycin (Sirolimus) slows aging, extends life span, and prevents age-related diseases, including diabetic complications such as retinopathy. Puzzlingly, rapamycin can induce insulin sensitivity, but may also induce insulin resistance or glucose intolerance without insulin resistance. This mirrors the effect of fasting and very low calorie diets, which improve insulin sensitivity and reverse type 2 diabetes, but also can cause a form of glucose intolerance known as benevolent pseudo-diabetes.

There is no indication that starvation (benevolent) pseudo-diabetes is detrimental. By contrast, it is associated with better health and life extension.

In transplant patients, a weak association between rapamycin/everolimus use and hyperglycemia is mostly due to a drug interaction with calcineurin inhibitors. When it occurs in cancer patients, the hyperglycemia is mild and reversible. No hyperglycemic effects of rapamycin/everolimus have been detected in healthy people.

For antiaging purposes, rapamycin/everolimus can be administrated intermittently (e.g., once a week) in combination with intermittent carbohydrate restriction, physical exercise, and metformin.

Rapalogs

line drawing of scientist looking into a microscope

What Are Rapalogs?

Rapalogs are drugs that work similarly to rapamycin, the most reliably life-extending drug.  Rapamycin was discovered in 1972 in a bacterium called Streptomyces hygroscopicus on the island of Rapa Nui (aka Easter Island).  It was initially developed as an antifungal, but later it was found that it inhibits the mTOR pathway, which regulates cell growth, cell proliferation, and cell survival. Recently, other drugs have been found which also inhibit mTOR.

Rapamycin is an immunosuppressant used to prevent organ transplant rejection; it has serious side effects in humans, including infections and low platelet counts, so it’s unlikely to be usable as an anti-aging preventative, though there are some studies suggesting that low-dose rapamycin may be safe.  

A few rapalogs have been found to have anti-aging effects in animals, but none have been shown to increase mouse lifespan so far.

LEARN MORE: The Lifespan Research Institute