Bacteria, both invasive and symbiotic, play their parts in the progression of our biochemistry from young to old. Here I'll point out a couple of interesting recent papers that are representative of the increased level of scientific community interest in what exactly is going on in bacterial populations over the course of aging. In this case the area of focus is the bacteria present in the mouth and the gut.
The first paper suggests that we might blame bacteria for some portion of the damaged or otherwise problematic lipids that contribute to the development of atherosclerosis. This is as opposed to, say, oxidative damage of native lipids as a result of mitochondrial dysfunction or other sources of oxidative stress in tissues. These damaged lipids enter the bloodstream where they can provoke an overreaction in blood vessel walls, leading to a runaway process of inflammation and cell death that over the years produces fatty deposits that narrow and weaken blood vessels. A rational process of walking through the various problem compounds found in atherosclerotic deposits in some order of priority, finding ways to safely break them down, such those of the LysoSENS programs, probably doesn't involve too much introspection about the origins of these compounds. It is more the case that a better understanding of those origins is helpful at this stage to construct the priority list - there are a lot of potential targets.
The second paper is something we're seeing more of these days, the delivery of a young bacterial population to old individuals, or vice versa. The balance of microbial species in the gut changes with age in what are beginning to appear to be fairly characteristic ways, one more secondary consequence of the underlying damage and disruption of aging that is argued to itself go on to create further harms. Raised levels of chronic inflammation are the most likely mediating mechanism for those further harms: inflammation speeds the development of all of the common age-related diseases.
There is, I think, sufficient evidence already to say that changing gut bacteria populations contribute secondary harms in aging. For example, a transplant of gut microbes from young killifish to old killifish extends life. More evidence in mammals rather than fish can't hurt, however. Neither say a great deal about how important this all is in human aging, of course. Short-lived species have very plastic life spans, exhibiting large changes in response to circumstances that, while they certainly impact health in our species, don't do much to human life span. We might imagine that the various effects of exercise, obesity, and calorie restriction place likely bounds on the size of the benefits that might be achieved by maintaining or failing to maintain youthful bacterial populations.
Microorganisms of the phylum Bacterioidetes are prevalent in the human intestinal flora and within this phylum, members of the Bacteroides genera represent approximately one-third of the cultivable microbial flora of the human intestinal microbiome. Periodontal diseases are also associated with increased percentages of specific Bacteroidetes species at periodontal disease sites. Porphyromonas gingivalis is considered to be a primary pathogen for chronic destructive periodontal disease. P. gingivalis has also been implicated in the development of atherosclerosis in experimental animals and P. gingivalis genomic products have been identified in a limited percentage of human atherosclerotic artery samples. In contrast to the atherogenic members of the oral flora, little is known regarding the capacity of intestinal organisms, particularly intestinal Bacteroidetes organisms, to contribute to the development of atherosclerosis.
Serine dipeptide lipids are produced by common oral and intestinal Bacteroidetes bacteria and the serine dipeptide lipids produced by P. gingivalis engage human and mouse Toll-like receptor TLR2. The serine lipids of P. gingivalis are comprised of two classes. One class is termed Lipid 430 and contains a single hydroxyl fatty acid linked to a serine-glycine dipeptide. The other class, termed Lipid 654, contains two fatty acids. Our work has shown that Lipid 654 engages TLR2. We have demonstrated that human blood sera samples contain detectable levels of Lipid 654 and lipid extracts of diseased periodontal tissues also contain Lipid 654. Therefore, accumulation of Lipid 654 in human tissues represents the presence of an exogenous TLR2 ligand produced by organisms of either the oral cavity or intestinal tract. TLR2 has been shown in experimental animal models to be an important innate immune receptor in the development of atherosclerosis.
The first goal of this investigation was to determine whether Lipid 654 is recovered in lipid extracts of common intestinal and oral Bacteroidetes, as well as in lipid extracts of human carotid artery tissue, brain, and blood samples. The median Lipid 430/Lipid 654 ratio was significantly elevated in carotid artery tissue when compared with control artery samples. Our results indicate that deacylation of Lipid 654 to Lipid 430 likely occurs in diseased artery walls due to phospholipase A2 enzyme activity. These results suggest that commensal Bacteriodetes bacteria of the gut and the oral cavity may contribute to the pathogenesis of TLR2-dependent atherosclerosis through serine dipeptide lipid deposition and metabolism in artery walls.
Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer's patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray.
Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.