Metformin and Rapamycin: Two Longevity Drugs We Should Consider Giving to Elderly, High-Risk Individuals

by Mike Mutzel

1 comment

Metformin and Rapamycin, two popular longevity drugs, have been shown to support immune health in elderly and high-risk subjects, here's the science.




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Articles Mentioned:

Bischof, E., C Siow, R., Zhavoronkov, A., & Kaeberlein, M. (2021). The potential of rapalogs to enhance resilience against SARS-CoV-2 infection and reduce the severity of COVID-19. The Lancet Healthy Longevity, 2(2), e105–e111.


Bramante, C. T., Buse, J., Tamaritz, L., Palacio, A., Cohen, K., Vojta, D., et al. (2021). Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity. Journal of Medical Virology, 93(7), 4273–4279.

Kruglikov, I. L., Shah, M., Elife, P. S.,. (2020). Obesity and diabetes as comorbidities for COVID-19: Underlying mechanisms and the role of viral–bacterial interactions.

metabolism, A. S. D.,. (2020). Metformin and COVID-19: from cellular mechanisms to reduced mortality. Nutrition, Metabolism and Cardiovascular Diseases.

Time Stamps:

01:10 Metformin and Rapamycin have a low side effect profile and have many upsides.

02:20 Metformin’s first application was to enhance recover from influenza. It is one of the most prescribed drugs for prediabetes, diabetes, and type-2 diabetes.

03:00 Mechanisms that support metabolic health improve the body’s immune response. As you age, you become more insulin resistant, and your immune system looses is competence. Cancer proliferates when you have immune incompetence.

05:09 Your immune system loses its efficacy with ageing, called immunosenescence. It effects both the innate and adaptive immune system. It greatly reduces production of T cells and B cells. Antibodies are made by B cells. T lymphocytes help instruct and orchestrate adaptive immunity by your B cells.

06:10 Decreased antibody production leads to fewer T cell and B cell interactions and reduced release of thyroid hormone. It leads to a decrease in natural killer cell activity.

06:30 Older people are more prone to have chronic low-grade background proinflammatory status, as well as elevated plasma markers, interleukin 6, TNF alpha, and CRP.

06:55 Interleukin 6 is correlated with viral load. It is a sign of a stressed immune system and insufficient initial immune response. A proxy measurement of interleukin 6 and TNF-alpha is high sensitivity C-reactive protein.

07:30 Background smoldering inflammation translates to enhanced inflammatory activity, especially in monocytes and macrophages of the innate immune system. It is linked to the acceleration of insulin resistance and worsening of glycemic control with ageing.

08:45 The relationship between chronologic age and poor COVID 19 outcomes, may be driven by biologic ageing mechanisms.

09:20 Infrequent micro dosing (5 mg) of rapamycin can promote regeneration within the immune system.  Rapamycin is used daily in high doses in transplantation patients to suppress the immune system.

10:30 Both Metformin and Rapamycin have been shown to improve immune response to a flu vaccination and have lasting favorable reductions in illness long after the drug has been stopped.

10:45 Your immune system cross talks with your microbiome. A dysregulated immune system may correspond with an altered microbiome.

11:45 Micro dose recommended amount is 5 – 10 mg one day a week for individuals over the age of 60 who are biologically aged at least 5 years older. This is periodic, not continuous.

14:20 Metformin is derived from a natural compound. Berberine functions similarly to metformin. Rapamycin is made from a bacterium.

15:28 Poor glycemic health is a predictor of mortality/death.  Glycemic variability (aberrant blood sugar levels) is linked with mortality.

16:23 If you go into the hospital with COVID and your blood sugar is very high, the probability of your survival after 40 days is zero. This compares to people admitted to the hospital with normal blood sugar. They have an 80% probability of survival after 40 days.

16:40 Hyperglycemia enhances coagulation/clotting and reduced neutrophil degranulation in systemic inflammation, even when you do not have a history of diabetes.

18:10 Methyl B 12 and folate are depleted when you are taking Metformin.

18:20 Outpatient Metformin use is associated with reduced severity of COVID 19 in adults with overweight or obesity.  Studies have shown a reduction in disease severity and hospitalization with Metformin use.

19:30 High levels of hemoglobin A1C is linked to poor outcomes, with various diseases and all-cause mortality. A1C is a look at long term blood average glucose levels.

Related: Latest Breakthroughs In the Biology of Aging with Matt Kaeberlein, PhD




  1. HI Mike:

    I would suggest that Metformin is NOT a good choice for healthy aging purposes.
    It has been shown in the literature to negatively impact on exercise performance and as well to compromise mitochondrial activity.

    Here are a couple of representative papers to support this:

    Metformin directly acts on mitochondria to alter cellular bioenergetics

    Results: We show that metformin decreases mitochondrial respiration, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, cells treated with metformin become energetically inefficient, and display increased aerobic glycolysis and reduced glucose metabolism through the citric acid cycle.


    Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults

    Metformin and exercise independently improve insulin sensitivity and decrease the risk of diabetes. Metformin was also recently proposed as a potential therapy to slow aging. However, recent evidence indicates that adding metformin to exercise antagonizes the exercise-induced improvement in insulin sensitivity and cardiorespiratory fitness.

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