The Aging of the Gut Microbiome from a DNA Damage and Telomere Erosion Perspective
Researchers here focus specifically on DNA damage and telomere erosion as hallmarks of aging, and discuss mechanisms by which changes in the microbial populations of the body (primarily the gut microbiome) can indirectly influence these outcomes. Unsurprisingly, inflammation is high on the list. With age, beneficial microbial species decline in number to be replaced by an expanded pool of species capable of provoking continual, unresolved inflammatory reactions as they interact with tissues and the immune system. Evidence suggests that this is an important contribution to the state of low-grade inflammation that is characteristic of older individuals, and thus to degenerative aging, disruptive to tissue structure and function.
Aging is not a singular event but a complex interaction of numerous inherent and external factors that together shape the timing and nature of the process. Among these factors, the human microbiome has emerged as an important influence on host physiology and health outcomes. Dysbiosis, or imbalances in the microbiome, is linked to age-related conditions such as cardiovascular diseases (CVDs), neurodegenerative diseases (NDs), and metabolic syndromes.
DNA repair mechanisms and cell cycle checkpoints protect genetic material, ensuring its stability across cell generations. However, internal and external factors continuously threaten this stability by causing DNA damage. An important factor in cellular aging is the progressive shortening of telomeres, repetitive DNA sequences found at the ends of chromosomes. Telomeres protect chromosomal ends, preventing them from being mistaken for DNA breaks and maintaining genomic stability. However, with each cell division, telomeres shorten because DNA polymerase cannot fully replicate the lagging strand. As a result, telomeres act as a molecular timer, restricting the ability of cells to proliferate and leading to replicative senescence. Understanding how the human microbiome, genomic stability, and telomere shortening are interconnected is crucial to uncovering the mechanisms of aging and developing strategies for healthy aging.
This review examines how microbiome dynamics influence aging by triggering inflammation, oxidative stress, immune dysregulation, and metabolic dysfunction, all of which affect two primary hallmarks of aging: genomic instability and telomere attrition. Understanding these interactions is essential for developing targeted interventions to restore microbiome balance and promote healthy aging, offering potential treatments to extend healthspan and alleviate aging-related diseases. The convergence of microbiome and aging research promises transformative insights and new avenues for improving global population well-being.