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Although aging is an inevitable process, it can also be considered as a disease with genetic and environmental factors modulating its rate of progression and incidence of comorbidities. There are known molecular and cellular hallmarks of aging which include features such as
Together these features come together to deplete pools of stem cells, which prevents appropriate tissue regeneration, and alters cell-to-cell communication leading to a functional breakdown over time. In a 2020 systematic review entitled “The gut microbiome, aging, and longevity: a systematic review”, Badal et al dive into the age-associated changes in microbiota diversity, composition, and function. Here, we will provide an overview of their findings and the actionable implications.
With the emergence of the microbiome as a key player in both health and disease, it is becoming increasingly clear that the gut ecosystem is a central contributor to longevity across species. Importantly, not only do host-microbiota interactions influence aging, but aging also has physiological and metabolic effects that influence the microbiome.
The microbiome is now recognized as a primary determinant of immune function, and dysbiosis may sustain pro-inflammatory states chronically. Indeed, the “inflammaging” hypothesis of aging is now becoming widely accepted as the major driver of an unhealthy aging process. Inflammaging increases the incidence of cardiovascular disease, metabolic dysfunction, sarcopenia, and cognitive decline. Because the microbiome is a key regulator of immune cell inflammatory-anti-inflammatory balance, the cultivation of a healthy gut ecosystem helps to prevent the propagation of superfluous inflammation that drives tissue degeneration over time. Moreover, the microbes within the gut can communicate with the brain via the gut-brain axis and the production of key metabolites that influence not only cognition but also immunity and hormone balance. To this end, microbiome research offers an entry point within which to study both the physical and mental aspects of aging.
There are two primary measures of diversity used within microbiome research.
Alpha diversity corresponds to the diversity within a sample, and is often expressed as the richness or evenness of a sample. Low alpha diversity is typically associated with gut dysbiosis. Conversely, beta diversity measures the difference in diversity between samples.
Among the studies sampled, three reported that long-lived adults possessed higher alpha diversity, while a fourth showed higher alpha diversity among a set of core microbiota taxa. Across a lifespan, alpha diversity was shown to be lowest in infancy, with diversity increasing through adolescence and into young adulthood. Subsequently, diversity levels remained stable throughout the decades of adulthood, and ended higher in older adults and the elderly. With regards to cognition, lower alpha diversity was shown to be associated with slower reaction time, lessened verbal acuity, and overall poorer cognition. Additionally, lower levels of alpha diversity correspond to the presence of metabolic and inflammatory illnesses. Overall, alpha diversity is higher in individuals undergoing a healthy aging process. This increased diversity may make the microbiome more flexible and resilient to insults such as infections or medications.
With regards to beta diversity, five studies meeting the inclusion criteria showed significantly different beta diversity between the elderly and young control groups. Differences were also observed among the older adults and the elderly. Across lifespan, aging was associated highly with differences in beta diversity. In other words, beta diversity can serve as a proxy for age, with higher beta diversities corresponding to older adults.
Differences in bacterial taxonomic composition and function varied across the sampled studies. However, despite this variance, Akkermansia was the taxa most consistently reported as more abundant in the elderly. Meanwhile Faecalibacterium, Bacteroidaceae, and Lachnospiraceae showed relative reductions especially among the elderly. With regards to functional output, older adults exhibit decreased expression of microbial pathways related to carbohydrate metabolism and amino acid synthesis relative to younger adults. However, the elderly possessed increased expression of the pathways associated with short chain fatty acid (SCFA) production, enhanced cellular respiration, and vitamin synthesis relative to older adults.
In adults, there are two primary phyla residing within the gut:
The elderly were shown to have lower Firmicutes relative to Bacteroidetes, which is consistent with previous findings showing that the ratio of Firmicutes to Bacteroidetes increases with age, but then begins to decline once more in older age. Importantly, however, the Firmicutes-to-Bacteroidetes ratio was also highly dependent upon the environment of the elderly individuals, with striking differences observed between community-dwelling elders versus hospitalized elders. These findings suggest that the equilibrium between these two phyla may be an important metric of health and longevity if environmental factors are also considered.
Key taxa have been previously associated with healthy aging and anti-inflammation. These include:
Akkermansia was the genus most frequently observed in the elderly, and the literature cites Akkermansiaand Christensenellaceaeas being associated with improved metabolic health including decreased risk of type 2 diabetes, cardiovascular disease, and lower BMI. Akkermansia muciniphila is one of the only species of Verrucomicrobia currently characterized, and it is reported to promote intestinal barrier integrity and reduce the toxic effects of a high-fat diet. Within the studies that looked at the relationship between the microbiome and cognition in older adults, it was observed that individuals with higher levels of Verrucomicrobia performed better on various psychomotor tasks, had increased learning capabilities, and improved sleep quality. To this end, the research suggests that Verrucomicrobia including Akkermansia, as well as Christensenellaceaemay facilitate healthy aging by improving body composition, reducing inflammation, and decreasing risk for metabolic dysfunction and the associated cognitive declines.
Conversely, Proteobacteria was shown to be more abundant in the elderly than in older adults and younger adults. Proteobacteria has previously been shown to correspond to increased dysbiosis and gut inflammation. In addition, Faecalibacterium was shown to be less enriched in the guts of the elderly. Faecalibacterium is a primary producer of the key SCFA butyrate. Although these observations appear to be contradictory at first blush, these patterns essentially indicate that there is a balance present between key bacteria within the gut in the elderly. Along these lines, previous research suggests that, in centenarians, there is a delicate balance of pro-inflammatory and anti-inflammatory activity, representative of the healthy immune function required for longevity.
The composition and functional capacity of the microbiome is largely shaped by both short- and long-term dietary patterns. During the aging process, there are a variety of factors that limit gut microbe access to nutrients including:
To this end, it is crucial to be vigilant about dental health and maintenance of a balanced diet throughout the aging process to promote longevity. The Mediterranean diet—characterized by high consumption of vegetables, legumes, nuts, fruits, olive oil, and fish—has been reported to improve health and reduce risk of various chronic age-associated illnesses including neurodegeneration, cancers, and cardiovascular disease. Indeed, previous studies have reported a lower Firmicutes-to-Bacteroidetes ratio, higher levels of Christensenellaceae and Faecalibacterium prausnitzii, increased alpha diversity, and increased levels of SCFAs in individuals adhering to a Mediterranean diet.
Longevity encompasses both genetic and environmental factors, and is associated with an increased flexibility and stability of the microbiota. Although inflammation is generally thought of as “bad”, a balance of inflammatory and anti-inflammatory activities emerges as a hallmark of centenarians indicating that both poles of the immune system are essential for a long life. Finally, environmental factors such as diet play a major role in shaping the microbiome in both the short- and long-term. Thus, an emphasis should be placed on the consumption of a micronutrient-rich diet during aging to facilitate a healthy microbial balance within the gut.
Badal VD, Vaccariello ED, Murray ER, Yu KE, Knight R, Jeste DV, Nguyen TT. The Gut Microbiome, Aging, and Longevity: A Systematic Review. Nutrients. 2020 Dec 7;12(12):3759. doi: 10.3390/nu12123759. PMID: 33297486; PMCID: PMC7762384.
