Fight Aging!

In today's open access paper, researchers discuss immunization with Mycobacterium vaccae as an approach to reduce the inflammatory overactivity of the aged immune system. Researchers have made some initial inroads into studying the way in which this bacteria can alter the function of the immune system, and here the focus is on immune cells in the brain. A growing body of evidence points to microglia, innate immune cells of the central nervous system, as an important contributing cause of age-related neurodegeneration. These cells react to increased molecular damage, inflammatory signaling generated by senescent cells, and so forth, all of which is far more prevalent in the old brain than in the young brain. They become activated and inflammatory. The result is chronic inflammation in brain tissue and consequent disruption of cell and tissue function.

From a self-experimenter's perspective, Mycobacterium vaccae immunization is an interesting approach. Large clinical trials of Mycobacterium vaccae immunization have taken place for reasons unrelated to inflammation, and thus a good deal of safety data already exists. A quick look online suggests that it is practical to purchase Mycobacterium vaccae in a useful form, given a little work. The protocol used in rats in the paper here is as simple as a few weekly injections of a small amount of bacteria. While it is next to impossible to assess what is going on in the microglial population of the human brain, there are plenty of assays that might be used to assess the burden of systemic inflammation. That said, this is an initial observation that needs more research and reading to back it up; it may not be as interesting as it seems at first glance.

Mycobacterium vaccae immunization in rats ameliorates features of age-associated microglia activation in the amygdala and hippocampus

The lengthening of the human lifespan is associated with a rise in the burden of age-associated neurological disorders. Indeed, the aging process is characterized by a progressive shift from a homeostatic balance of inflammatory markers towards a "primed" or sensitized state. This increased neuroinflammatory priming makes the aged brain further susceptible to the disruptive effects of intrinsic and extrinsic factors like disease, infection, and stress, thereby elevating the risk of affective disorders, cognitive impairments, and neurodegenerative diseases in the aged population.

In addition to aging, chronic inflammatory conditions are increasing. Elevated chronic low-grade inflammation among modern urban societies may be caused by decreased microbial exposures - this is the foundation for the "Old Friends" hypothesis. Throughout evolution, the mammalian immune system developed tolerance to commensal environmental microbes. One such example is Mycobacterium vaccae (M. vaccae), a saprophytic bacterium found in soil, water, and mud that our ancestors frequently encountered. Reintroduction of these microbes in an excessively "clean" environment can suppress immune sensitization and reduce the risk for inflammatory diseases. M. vaccae has immunoregulatory properties, such as enhancing the induction of regulatory T cells and stimulating their production of anti-inflammatory cytokines, including interleukin (IL)-10 and transforming growth factor β. Peripheral immunization with M. vaccae also promotes an anti-inflammatory milieu in the central nervous system (CNS).

Elevated neuroinflammatory priming, as is observed due to aging, is mediated in part by microglia, the primary immunocompetent cell in the CNS. Microglia are dynamic cells that take on an array of phenotypes based on signals from their surrounding microenvironment. When microglia detect adverse signals or molecules, their morphology can drastically change.

Here, we investigate whether aging-related shifts in microglial morphology are ameliorated by immunization with anti-inflammatory M. vaccae. Morphological features of microglia evaluated in the amygdala, hippocampus, hypothalamus, and prefrontal cortex of adult (3 mos) and aged (24 mos) male rats. Our results demonstrate that aging leads to differential changes in microglia morphology and reactivity across brain regions, with the hippocampus being the most sensitive. Moreover, microglia in the amygdala and hippocampus appear most responsive to the anti-inflammatory effects of M. vaccae immunization, protecting against some age-associated microglia morphological changes.