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How Gut Microbes Influence Aging and Inflammation

Research is increasingly finding a link between the aging process and the lifelong exposure to pathogens. Researchers in this recent study kept mice in a germ-free environment and found that the mice had significantly lower levels of inflammation and a marked improvement in their average lifespan [1].

This correlates with another study where mice were raised in a germ-free environment and they accumulated less amyloids in the brain during their lives [2].

The researchers in this new study have studied the interaction between the gut microbiota and the immune system and its influence on aging. Populations of microbes in the gut can have a long-term effect on health and research is exploring this relationship. In a broad sense, the long-term health of the gut might be considered on par to regular exercise as part of a personal health and longevity strategy.

This is based on the fact that the most impressive effects on lifespan thus far are obtained via caloric restriction, and that the manipulation of the gut microbiota is yet to yield results in the same league. Nevertheless as this research shows, microbial burden does appear to play a significant role in aging.

Microbial burden

There is good supporting evidence to suggest that decline of the immune system can be accelerated by exposure to persistent pathogens such as cytomegalovirus (CMV)[3-4]. CMV is a type of virus from the herpes family and is extremely common, it is thought that between 50-80% of the US population has contracted this virus by age 40.

The CMV virus is a problem, as the body cannot effectively combat it and so it increases in numbers putting an increasing strain on the immune system as we age. CMV is one example of persistent pathogens that remain in the body and cannot be removed, but there are others.

This microbial burden likely contributes to the decline of the immune system (known as immunosenescence) and is an influence on the aging hallmark: altered intercellular communication, helping to drive the smoldering chronic inflammation known as inflammaging[5].

Inflammaging results from multiple causes, such as the accumulation of proinflammatory tissue damage, the failure of an ever more dysfunctional immune system to effectively clear pathogens and cell debris, persistent pathogens, and accumulated senescent cells secreting proinflammatory cytokines.

Inflammation drives the aging process

These sources create inflammation, which changes the signalling environment and increasingly reduces the regenerative capacity of tissue as we age.

Short term inflammation is a beneficial and necessary part of how the immune system works; however, chronic inflammation associated with aging is not. As the immune system becomes increasingly dysfunctional, it drives excessive inflammation, causing damage, and leads to the progression of various age-related diseases. There is a good chance that microbial burden plays a significant part in this downward spiral.

In fact, we can even look at humans as a comparison to the new study to see the effects of reduced exposure to pathogens on long-term health and lifespan. Historically, as medicine and hygiene have improved, our exposure to pathogens has been reduced and aged people today are generally less physically frail than people a century ago. In general people tend to age better, and even a few generations ago people often looked older than people the same age now do; some of this is almost surely down to a reduction of pathogen exposure.

Where microbial burden falls in the hierarchy of aging is less clear. Does microbial burden cause the immune system to fail or does the failing immune system allow microbial burden to increase?

For example, as we age, the thymus begins to shrink and produce fewer and fewer T-cells to help protect us from infections and viral invaders; so, is it a case that this decline permits microbes to infiltrate and evade destruction, or do the microbes actually contribute to the immune system failing, causing it to become weaker over time?

The situation is at this point far from clear, and research like this is critical in helping us get to the bottom of this mystery.


Microbial burden no doubt plays a significant role in aging of the immune system, and as an aged immune system influences so many processes of aging, it makes sense to try to keep your gut healthy.

If you are interested in learning more about microbial burden and optimizing your gut for health and longevity, we recommend reading “Microbial Burden: A Major Cause Of Aging And Age-Related Disease” by Mike Lustgarten.


[1] Thevaranjan, Netusha et al. (2017).Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction. Cell Host & Microbe , Volume 21 , Issue 4 , 455 – 466.e4
[2] Harach, T., Marungruang, N., Duthilleul, N., Cheatham, V., Mc Coy, K. D., Frisoni, G., … & Bolmont, T. (2017). Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota. Scientific Reports, 7.
[3] Cicin-Sain, L., Brien, J. D., Uhrlaub, J. L., Drabig, A., Marandu, T. F., & Nikolich-Zugich, J. (2012). Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging. PLoS pathogens, 8(8), e1002849.
[4] Khan, N., Hislop, A., Gudgeon, N., Cobbold, M., Khanna, R., Nayak, L., … & Moss, P. A. (2004). Herpesvirus-specific CD8 T cell immunity in old age: cytomegalovirus impairs the response to a coresident EBV infection. The Journal of Immunology, 173(12), 7481-7489.
[5] López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.

About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 600 articles on the topic, interviewed over 100 of the leading researchers in the field, hosted livestream events focused on aging, as well as attending various medical industry conferences. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, Swiss Monthly, Keep me Prime, and New Economy Magazine. Steve is one of three recipients of the 2020 H+ Innovator Award and shares this honour with Mirko Ranieri – Google AR and Dinorah Delfin – Immortalists Magazine. The H+ Innovator Award looks into our community and acknowledges ideas and projects that encourage social change, achieve scientific accomplishments, technological advances, philosophical and intellectual visions, author unique narratives, build fascinating artistic ventures, and develop products that bridge gaps and help us to achieve transhumanist goals. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project.
  1. April 13, 2017

    Very interesting indeed, and another book added to my to-read list (that list is getting very long indeed).

    Thanks very much Steve!

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