Bacterial Stimulation of FOXN1 Theorized to Enhance Healthy Longevity

Researchers here theorize on the role of bacteria in stimulating immune function and other aspects of our biology in a positive way, with a focus on the FOXN1 protein. Increased FOXN1 in old mice has been demonstrated to restore the thymus to more youthful activity, and thus improve immune function. The thymus is where some classes of immune cell mature, and because it atrophies early in adulthood, the flow of new immune cells is much reduced over most of the life span. This low rate of production is a contributing factor to the age-related limits and decline of the immune system. Any method that rejuvenates the thymus, or that otherwise produces a large supply of new immune cells, will do a lot for immune function in old age. It isn't a fix for all of the issues by any means, but it is a fix for one of them, and in this new age of cheap and effective gene therapy, boosting the levels of individual proteins isn't an unreasonable thing to aim for in the years ahead.

The popularity of hand sanitizer and antibiotics shows how we feel about bacteria: an enemy that's bad for our health. Emerging data, however, suggest just the opposite - that exposures to certain kinds of bacteria are beneficial for a long and healthy life. Specifically, mice consuming probiotic L. reuteri were shown to have larger skeletal muscles than untreated age-matched controls. A surprising additional finding was increased thymus gland size only in mice consuming bacteria in their drinking water. The thymus was not only larger, but also had increased expression of Forkhead Box N1 (FoxN1), a feature involved in systemic programming of immune system lymphocytes.

Bacterial stimulation of FoxN1 and increased thymus gland size has enormous implications for host good health. Indeed, FoxN1 protein has been touted as a "Fountain of Youth". During childhood, a proficient thymus gland supplies adaptive immune cells that help fight pathogenic infections and discern self versus non-self, to lower risk of autoimmune diseases. With increasing age, the thymus gland naturally shrinks leading to immune dysregulation with higher risk for infections and cancer in elderly subjects. Other studies have shown that mouse models treated exogenously with FoxN1 had features of sustained youth. Interestingly, animals lacking FoxN1 failed to develop larger muscles after microbial therapy, implicating the immune system in muscle-boosting effects.

The precise mechanism by which bacteria stimulate FoxN1 expression in the thymus gland remains unknown but likely involves the wnt signaling pathway. Microbes have been shown by our own lab and by others to prime the immune system for sustained good health. At the same time, the thymus gland and muscle growth may also be stimulated through bacteria-triggered upregulation of central nervous system (CNS) hormones, for example growth hormone and oxytocin. Perhaps exposures to bacteria can be good for us, after all. Can we formulate a bacteria cocktail that prevents muscle loss with aging and imparts a long, healthy, and meaningful life? Additional research is needed to explore the vast and far-reaching potential of microbes for a long and healthy life.



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