Young at Gut-Turning Back the Clock with the Gut Microbiome

Abstract

Over the past century, we have witnessed an increase in life-expectancy due to public health measures; however, we have also seen an increase in susceptibility to chronic disease and frailty. Microbiome dysfunction may be linked to many of the conditions that increase in prevalence with age, including type 2 diabetes, cardiovascular disease, Alzheimer's disease, and cancer, suggesting the need for further research on these connections. Moreover, because both non-modifiable (e.g., age, sex, genetics) and environmental (e.g., diet, infection) factors can influence the microbiome, there are vast opportunities for the use of interventions related to the microbiome to promote lifespan and healthspan in aging populations. To understand the mechanisms mediating many of the interventions discussed in this review, we also provide an overview of the gut microbiome's relationships with the immune system, aging, and the brain. Importantly, we explore how inflammageing (low-grade chronic inflammation that often develops with age), systemic inflammation, and senescent cells may arise from and relate to the gut microbiome. Furthermore, we explore in detail the complex gut-brain axis and the evidence surrounding how gut dysbiosis may be implicated in several age-associated neurodegenerative diseases. We also examine current research on potential interventions for healthspan and lifespan as they relate to the changes taking place in the microbiome during aging; and we begin to explore how the reduction in senescent cells and senescence-associated secretory phenotype (SASP) interplay with the microbiome during the aging process and highlight avenues for further research in this area.

Keywords: aging; gut–brain axis; healthspan; immune system; inflammageing; interventions; lifespan; senescence-associated secretory phenotype.

Figure 1

The gut microbiome, immune system, and brain all cross-communicate and can be modulated by interventions to improve healthspan and lifespan. Some interventions (Section 4) may more directly impact one system, some may impact indirectly, such as the direct impact of diet (Section 4.2) and fecal transplant (Section 4.5), and the indirect impact of exercise (Section 4.8) on the gut microbiome. Nonetheless, the gut microbiome (Section 4.2, Section 4.3, Section 4.4 and Section 4.5), the brain (Section 2 and Section 4.8), and the immune system (Section 4.6 and Section 4.7) are all connected to one another, and along with age, change in one system can subsequently impact the other systems, ultimately impacting healthspan and lifespan as well. Moreover, the impact of individuals and combinations of interventions on the key players of healthspan and lifespan are still being explored (Section 5). (*) indicates that a drug more specifically improves healthspan for Alzheimer’s/Parkinson’s patients, whereas the other interventions are meant for a broader population. This figure was created with Biorender.com.