Ageing is an inevitable, intricate process that affects all living organisms, marked by various genetic hallmarks such as telomere shortening, genomic instability, and epigenetic alterations. Physical, biochemical, and metabolic transformations occur within the human body as time progresses. Among the myriad factors influencing ageing, the gut microbiome (GM)—a complex and dynamic community of microorganisms in our gastrointestinal tract—plays a crucial yet often overlooked role. This review delves into the intricate relationship between the gut microbiome and ageing, underscoring the microbiota-dependent mechanisms that govern ageing processes, and evaluates various interventions to foster healthy ageing by modulating the microbiome.
The dynamics of the gut microbiome are ever-changing from the moment of birth through to old age. The nature of one’s birth, whether through cesarean section or natural delivery, along with early dietary habits such as breastfeeding or formula feeding, plays a significant role in shaping the initial microbial landscape. In infancy, the microbiome showcases less diversity, with distinct differences observed between breastfed babies, who tend to have a microbiome dominated by Bifidobacterium, and those formula-fed, typically showing higher levels of Bacteroides. A well-established “core microbiome” emerges as individuals reach adulthood, pivotal in immune and metabolic regulation. The onset of puberty introduces further changes, particularly sex-related variations influenced primarily by hormonal shifts. For older adults, a notable decline in microbial diversity occurs, with an increase in microbes associated with frailty, such as Christensenellaceae, and a decrease in short-chain fatty acid (SCFA) producers, which are vital for combating age-related conditions like sarcopenia and osteoporosis.
The interplay between the gut microbiome and ageing-related disorders is profound. Age-associated alterations in the gut microbiome are closely linked with various neurodegenerative and metabolic diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Dysbiosis, a term for microbial imbalance, has been implicated in ‘inflammageing’—a persistent, low-grade inflammation that accelerates the ageing process and is associated with numerous conditions such as AD, PD, cardiovascular diseases, and Type 2 diabetes. A reduction in beneficial SCFA-producing bacteria and an increase in gut permeability exacerbate inflammatory responses, hastening the progression of these diseases.
Furthermore, the gut microbiome shapes the immune system throughout an individual’s life. Immunosenescence, the gradual deterioration of the immune system associated with age, is intricately linked to changes in the gut microbiome. A decrease in microbial diversity impairs the immune system’s capability to combat infections, posing a significant challenge in elderly populations. Research suggests that maintaining a balanced microbial environment could delay immunosenescence and bolster immune responses, thus diminishing susceptibility to infections and chronic age-related ailments.
The metabolic implications of the gut microbiome are equally significant. The microbiome influences the production of various metabolites, including SCFAs, polyamines, and reactive oxygen species (ROS), affecting metabolic pathways and the ageing process. SCFAs, such as butyrate, are particularly beneficial; they help prevent age-related physiological decline by enhancing the integrity of the intestinal barrier, modulating immune responses, and preventing cellular senescence. However, dysbiosis can disrupt these beneficial processes, contributing to the onset of metabolic disorders like obesity and insulin resistance.
Promising interventions for promoting healthy ageing include microbiome modulation through dietary means, such as the intake of prebiotics and probiotics. Probiotic strains like Bifidobacterium longum and Lactobacillus rhamnosus have been associated with improved immune function and reduced inflammation in older adults. Moreover, maintaining physical activity and a balanced diet are pivotal for sustaining a diverse and stable microbiome, essential for longevity and well-being in an ageing population.
In conclusion, the gut microbiome occupies a central position in the biology of human ageing, influencing a wide array of physiological functions from metabolism to immune health. By strategically modifying the gut microbiome through lifestyle changes and targeted interventions, we can potentially decelerate the ageing process, mitigate the risk of age-related diseases, and enhance overall healthy ageing.
More information: Rashmi Ira et al, Understanding Aging through the Lense of Gut Microbiome, Exploratory Research and Hypothesis in Medicine. DOI: 10.14218/ERHM.2024.00008
Journal information: Exploratory Research and Hypothesis in Medicine Provided by Xia & He Publishing Inc.
