What are the biological mechanisms by which centenarians manage to reach 100 years of age or more, significantly outliving near all of their birth cohort peers? This is a question that receives a great deal of interest in the research community and among the public at large. The answer that aging is a stochastic process of damage accumulation that produces a distribution of outcomes, and that some people are lucky, is not very satisfying. So a sizable amount of funding is directed towards analysis of factors that might robustly contribution to the longevity of centenarians: cultural transmission of good practices in long-lived families, longevity-promoting genetic variants, and the topic for today, longevity-promoting variations in the composition of the gut microbiome.
Amidst all of this, it is perhaps worth considering whether finding out why centenarians are so long-lived is actually worth all of the effort. Centenarians are frail, a shadow of their younger selves, and exhibit a sizable mortality rate. Is this really a desirable state to aim for? The research community has a very good list of the causative processes of degenerative aging, the forms of molecular damage that accumulate in aged bodies to produce dysfunction. It requires exactly zero further knowledge of centenarian biochemistry to be able put a great deal of effort into the development of potential rejuvenation therapies that are capable of repairing this damage. The end result of successful, comprehensive rejuvenation via damage repair will not be people who are as damaged and frail as today's centenarians.
Diverse factors have been associated with healthy or unhealthy aging such as demographic factors; prosociality level, physical and organic health status, mental health, lifestyle factors, and genetics. This converges in the concept of biological aging (BA), defined as the set of processes that cause organ deterioration over time. BA depends on the complex interaction of these factors, which can lead to a heterogeneous aging process across multiple organic systems, and correlate with a specific survival time and health or disease phenotype even in advanced ages. To deeply understand the mechanisms associated with aging and to identify potential targets for intervention to control or delay BA and the onset of diseases, it is necessary to study successful BA models. These models reflect phenotypes that are resistant to external stress factors with a favorable organic response. Centenarians, individuals with a chronological age (CA; defined as the number of years an individual has lived) equal to or greater than 100 years, constitute one such model of successful aging.
Currently, there is a significant knowledge gap from the translational perspective due to the evolutionary and exhaustive nature of aging research, which requires robust and reproducible omics studies on populations (specially in centenarians). These studies would aid in understanding precisely how modifiable and nonmodifiable factors impact the organic evolution of centenarians. Cellular senescence, epigenetic clocks, and alterations in stem cells, are some of the cellular and molecular processes that could theoretically reflect cellular proteodynamics, adaptation to aging, and the development of health phenotypes and prognosis during longevity. Having specific data on these mechanisms could facilitate the identification of aging biomarkers for cells, tissues, organs, or diseases, and predict the onset of age-related chronic diseases. However, there are not enough, studies to corroborate these hypotheses based on centenarians as a model of successful aging. Therefore, evidence regarding possible interventions to delay aging and prevent the onset of age-related chronic diseases into extreme ages remains weak and speculative.
The gut microbiota (GM) has been described as a biological and metabolic regulator of various organs and diseases. Age and diet, determinants in aging, are two factors directly related to the establishment and modification of the composition of the GM. To date, little discussion has taken place regarding the specific changes that occur in the long-lived population, which allow the establishment of an antioxidant system with characteristics similar to those of a young population, as a result of successful evolutionary adaptation. Although the specific mechanisms are unknown, this may possibly be one of the strongest reasons influencing life expectancy and healthy lifespan during aging.
To understand the possible impact generated by the GM, its changes, and the probable causes for successful aging, the aim of this review was to synthesize evidence on the role of the GM as a potential protective factor for achieving extreme longevity, using its relationship with centenarians. Evidence suggests that there are significant changes in the composition of the GM of centenarians, compared to other age groups, which could be associated with specific phenotypes of healthy aging, and be determinants in extreme longevity. However, numerous factors condition the establishment of the GM over time. The origin of the data is limited to certain countries with some blue zones. This field should be extensively studied in regions lacking data and determine the possible specific causal association between genera and species of microorganisms, and extreme longevity.
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