The prevalence of elderly, is expected to double by 2050. Scientific advancements in the prevention and treatment of disease have prolonged human life span however, the increased life span is not accompanied by an elevated health span. Aging is an irreversible biological process that can be defined using nine hallmarks: the deregulation of genetic, epigenetic, and immunological mechanisms (immune senescence), as well as mitochondrial dysfunction, cell senescence, stem cell exhaustion and faulty nutrient sensing and intercellular signaling. In this context, several recent studies suggest that the aging microbiome presents abnormally high instability and heterogeneity between hosts, while specific microbial signatures of age-related diseases have started to be revealed. Furthermore, increased gut permeability can amplify low-grade local and systemic inflammation, predisposing individuals to the onset of multi morbidity. Several studies have proposed that the intake of probiotics can fine tune the gut microbial composition to more favorable structures in a host-specific manner.
Probiotics and Aging
Cell senescence and the exhaustion of the regenerative mechanisms result in loss of tissue functionality, thus providing fertile ground for the onset of multi morbidity. Apart from cancer, neurodegenerative and musculoskeletal disorders; cardiovascular and metabolic disease also present with high frequencies in this demographic, as aging is a major risk factor for chronic inflammatory diseases, such as diabetes and atherosclerosis. In this context, cell senescence and telomere shortening in cardiac cells lead to the progressive degeneration of aortic valves and vascular cells, increasing risk for the incidence of stroke and cardiac arrest. Interestingly, the gut microbiota can present differences between pre diabetic and healthy individuals, as shown during the integrative human microbiome project. Indeed, it was found that insulin-resistant participants exhibited a specific metabolic profile, delayed inflammatory responses, and altered gut microbiome structure compared to insulin-sensitive participants. Importantly, this multilevel approach was efficient in pinpointing disease states prior to clinical manifestations.
New investigations
Refining Probiotic Research in the Elderly Aging is highly personalized process, and thus the genetic, metabolic and microbial signature of advanced age could differ between individuals. The results of novel studies may provide a basis for the differential pace of aging recorded in individuals, as well as the onset of (multi-)morbidity with age. The genetic component of age-related diseases was examined in a recent study, where it was found that diseases that present with late onset in the population, share a common genetic basis. Indeed, there is significant overlap between diseases in terms of loci implicated in longevity. The role of the gut microbiome in ageing is currently a hot topic of study. Microbial residents of the gut co-evolve with the host throughout life. The structure of the gut microbiome is stabilized at around three years of age; during adulthood the composition and function of these communities remain relatively stable, as they can be influenced by a plethora of genetic and environmental factors. Disease-specific microbial signatures during adulthood have been proposed by several studies, however in the case of aging, the gut microbiome undergoes tremendous changes leading to dysbiosis. A shared characteristic of the aging gut microbiome is that the diversity of the microbiome falls dramatically, presenting high inter individual variability. This new unstable composition favors the establishment and proliferation of pathobionts, such as Proteobacteria . These changes can trigger local and systemic inflammation, while also contributing to the weakening of the gut barrier integrity. More specifically, the population shifts result in changes in the metabolic profile of the gut microbiome. For instance, decrease in the populations of short-chain fatty acid (SCFA) producers, such as Akkermansia muciniphila, results in decreased production of acetate, butyrate and propionate, which display anti-inflammatory activity and preserve the function of the gut mucosa. It is important to note however, that these changes may not be exclusively associated to aging, but also to environmental factors, use of medications (for co-morbid diseases/antibiotics), as well as malnutrition. The gut microbiome can be easily manipulated extrinsically; however, the ability of probiotics to alter its structure and function is debatable. Studies on healthy adults have shown that the gut microbiome presents an individual-specific resistance to the colonization of probiotics that may be decreased after antibiotic treatments. Nevertheless, their ability to rehabilitate the structure and function of the gut microbiome is limited and may even have adverse effects by slowing down the full repopulation of the gut. In this light, the fact that the aged microbiome presents a decreased diversity could indicate that probiotic supplementation could more readily modify the gut microbiome. Undoubtedly, the integration of systems biology in probiotic research has unraveled the great complexity of their biological properties, also providing an explanation for contradicting clinical data and inconsistencies of clinical outcomes in individuals.
Conclusions
As the worldwide population is ageing rapidly, the need for expanding citizen health span is coming to the forefront. Age is considered an important risk factor for the development of debilitating disease that can increase the dependency of individuals and negatively affect their quality of life. The biological mechanisms of aging are starting to be revealed, and novel approaches, for more efficient management of multi morbidity have been developed. Probiotics that can modulate the root causes of aging, especially inflammation, oxidative stress and cell senescence could comprise useful tools in this direction. Despite the available literature on the beneficial effects of probiotic consumption on age-related diseases, no consensus has been reached for their use in clinical practice. This phenomenon could be attributed to the absence of meticulous characterization of the biology and mechanisms of action of probiotic strains that can enhance the lack of translatability of preclinical studies. Furthermore, current clinical studies present analytical drawbacks that can weaken their arguments and conclusions. With the dawn of the multi-omics era, the use of high throughput platforms to understand the complex host–microbiome–probiotic interactions, could enhance the efficacy and safety of probiotic consumption in the elderly. Conclusively, clinical studies with greater rigor and proper measurement of outcomes to evaluate and systematically classify the holistic effects of probiotic consumption, are required in order to design personalized approaches for the management of age-related disease.
prepared by: Nazila Kassaian
references
- Kiousi DE, Kouroutzidou AZ, Neanidis K, Matthaios D, Pappa A, Galanis A. Evaluating the Role of Probiotics in the Prevention and Management of Age-Related Diseases. International Journal of Molecular Sciences. 2022 Mar 26; 23(7):3628.
- Hutchinson, A.N.; Bergh, C.; Kruger, K.; S ˝usserová, M.; Allen, J.; Améen, S.; Tingö, L. The Effect of Probiotics on Health Outcomes in the Elderly: A Systematic Review of Randomized, Placebo-Controlled Studies. Microorganisms. 2021; 9: 1344.
