Help us: Donate
Follow us on:

Rapamycin, not Dietary Restriction, Fights Infection in Mice

"Feed a fever" may be good advice.

Infectious diseaseInfectious disease

A meta-analysis published in GeroScience has shown that the well-studied drug rapamycin has positive effects on infection in mice, but dietary restriction seems to worsen the problem.

Aging, immunity, and interventions

This paper begins with the well-known information that aging impairs the immune system, harming its effectiveness against infectious diseases [1] while causing systemic inflammation (inflammaging) [2]. Interestingly, while both rapamycin and dietary restriction are thoroughly documented interventions against aging, high-dose rapamycin is used in clinical settings as an immunosuppressant [3], and there is prior evidence that dietary restriction impedes immune function against pathogens [4].

This line of research has been explored many times in the past. Therefore, these researchers performed a study of studies, a true meta-analysis, in order to determine whether dietary restriction and rapamycin are helpful or harmful against infection.

Counterintuitive results

Rapamycin DR meta-analysis

While it is clear that not all of these studies agreed with each other, the researchers note that the standard Black 6 mouse and a standard 40% dietary restriction rate were common throughout. By thoroughly comparing these various studies, the researchers found that dietary restriction slightly but significantly increased the risk of pathogen infection, while rapamycin treatment significantly decreased it, particularly in secondary infections. There did not seem to be evidence of publication bias, and the type of pathogen did not seem to matter either. However, the researchers do note that the sex of the mice, a frequent confounding factor, was not reported enough to be used as part of the meta-analysis.

The researchers note several aspects of these findings. Caloric restriction has been previously reported to youthen the immune system, such as by protecting T-lymphocytes from oxidative damage [5]. However, it decreases leptin, which has been shown to reduce the effectiveness of natural killer cells [6]. Rapamycin, on the other hand, increases the population of T regulatory cells [7] and improves immune memory [8], which could explain its effectiveness against secondary infections.


This meta-analysis serves as a sharp reminder that while systemic immune overactivation is a key part of age-related diseases, underactivation has its own obvious problems as well. Treatments to fight inflammaging need to allow the immune system to perform its original, core function. Furthermore, while these studies were done on mice rather than people, practitioners of caloric restriction might also want to keep these results in mind.

We would like to ask you a small favor. We are a non-profit foundation, and unlike some other organizations, we have no shareholders and no products to sell you. We are committed to responsible journalism, free from commercial or political influence, that allows you to make informed decisions about your future health.

All our news and educational content is free for everyone to read, but it does mean that we rely on the help of people like you. Every contribution, no matter if it’s big or small, supports independent journalism and sustains our future. You can support us by making a donation or in other ways at no cost to you.

Senolytic Improves Metabolism in Mice

Scientists have shown that a popular senolytic combination of dasatinib and quercetin improves glucose tolerance and fasting blood glucose levels...

A Light-Sensitive Drug to Remove Senescent Cells

Research published in Nature Aging has shown that a photosensitive senolytic drug can be used to selectively remove senescent cells,...

Ultrasound Rejuvenates Senescent Cells Through Autophagy

In a preprint paper, the researchers have shown that low-frequency ultrasound treatment decreases senescence and improves the physical performance of...

Rejuvenation Roundup January 2023

As 2023 continues, so does new research into rejuvenation, regeneration, and restoration. Let's see what's been done to reverse age-related...


[1] Gavazzi, G., & Krause, K. H. (2002). Ageing and infection. The Lancet infectious diseases, 2(11), 659-666.

[2] Baylis, D., Bartlett, D. B., Patel, H. P., & Roberts, H. C. (2013). Understanding how we age: insights into inflammaging. Longevity & healthspan, 2(1), 1-8.

[3] Saunders, R. N., Metcalfe, M. S., & Nicholson, M. L. (2001). Rapamycin in transplantation: a review of the evidence. Kidney international, 59(1), 3-16.

[4] Speakman, J. R., & Mitchell, S. E. (2011). Caloric restriction. Molecular aspects of medicine, 32(3), 159-221.

[5] González, O. A., Tobia, C., Ebersole, J. L., & Novak, M. J. (2012). Caloric restriction and chronic inflammatory diseases. Oral diseases, 18(1), 16-31.

[6] Clinthorne, J. F., Adams, D. J., Fenton, J. I., Ritz, B. W., & Gardner, E. M. (2010). Short-term re-feeding of previously energy-restricted C57BL/6 male mice restores body weight and body fat and attenuates the decline in natural killer cell function after primary influenza infection. The Journal of nutrition, 140(8), 1495-1501.

[7] Canivet, C., Menasria, R., Rhéaume, C., Piret, J., & Boivin, G. (2015). Valacyclovir combined with artesunate or rapamycin improves the outcome of herpes simplex virus encephalitis in mice compared to antiviral therapy alone. Antiviral research, 123, 105-113.

[8] Keating, R., Hertz, T., Wehenkel, M., Harris, T. L., Edwards, B. A., McClaren, J. L., … & McGargill, M. A. (2013). The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nature immunology, 14(12), 1266-1276.

About the author
Josh Conway

Josh Conway

Josh is a professional editor and is responsible for editing our articles before they become available to the public as well as moderating our Discord server. He is also a programmer, long-time supporter of anti-aging medicine, and avid player of the strange game called “real life.” Living in the center of the northern prairie, Josh enjoys long bike rides before the blizzards hit.
No Comments
Write a comment:


Your email address will not be published.

This site uses Akismet to reduce spam. Learn how your comment data is processed.