The goal of current approaches to anti-aging in humans is to reduce the excess growth and development signal to the cells and enhance the repair system of the cells in order to maximize DNA repair and increase autophagy. Autophagy is the normal process used by the body to remove defective proteins, cell components, and even entire defective cells, so they can be replaced by new healthy ones. We know what stimulates autophagy and many supplements and drugs are now used by people interested in slowing their rate of aging. Drugs and supplements that stimulate autophagy are called senolytic drugs. I will review them in this post. But first, lets discuss fasting.
Fasting is a powerful inducer of autophagy, whether intermittent or longer term. Eating a lower calorie diet with adequate protein and micronutrients has been shown to improve health and extend the lifespan of all organisms it has been studied in. Many of the long-lived people of the world eat a lower calorie but nutritious diet and incorporate fasting traditionally.
What supplements can activate autophagy? Here is a partial list, which I discuss with my patients, when creating an antiaging program for them:
NMN (nicotinamide mononucleotide) and NR(nicotinamide riboside), both forms of vitamin B3, increase NAD+ which is a key energy source for certain important enzymes such as sirtuins which repair the epigenetic controls and also activates autophagy. Resveratrol, Quercetin, Fisetin, Curcumin, Spermidine and Urolithin are also powerful activators of autophagy. There are now supplements that combine many such autophagy activators and are called "senolytics", meaning they eliminate old cells, and are typically taken once per month.
Other helpful antiaging supplements include N-Acetyl Cysteine and Glycine, and Taurine, which boost the antioxidant Glutathione, Astaxanthin, TA65 (an extract of astralagus), oxaloacetate.
Exercise can stimulate autophagy, particularly high-intensity exercise.
Optimizing nutrition is important to prevent micronutrient deficiencies, so taking a good multivitamin, omega 3 fats, supplementl D3 and K2 is important.
What about drug therapy for aging? Well, it turns out that several already approved drugs may be effective senolytics and act to induce autophagy. These include the combination of Dasatanib and Quercetin or Fisetin and the drugs Rapamycin and Metformin. Several human trials have shown beneficial results when treating the patients with Dasatanib+Quercetin intermittently, Rapamycin has been tested on animals and has improved longevity by reducing mTOR activity which triggers cell division and activating autophagy, mimicking the effect of fasting, and reducing inflammation. Studies are ongoing to see what effect it has in humans, but many people are taking it in the meantime, typically on a once per week dosing schedule. Metformin activates AMPK, which triggers autophagy similar to fasting; it is typically prescribed to diabetics. Studies of diabetics show reduced rates of cancer, cardiovascular complications, and longer life vs. patients who did not receive this drug. Based on this research, and the mechanism of action, many people take metformin daily, even if not diabetic, to slow the rate of aging.
An interesting recent study showed that using human growth hormone+metformin and DHEA reduced patients epigenetic age; this pilot study is being repeated with a larger group of patients to confirm the surprising results.
These are just the highlights of the current approach many people are using to improve their healthspan and hopefully slow the rate of aging. If you would like to discuss this complex topic further, please schedule an appointment with me.
