Does the Gut Microbiome Contribute to Frailty via Oxidative Stress?

The challenge in understanding degenerative aging is at this point less a matter of identifying mechanisms, and more a matter of establishing which of the many mechanisms involved in every specific aspect of aging are actually important. Cellular biochemistry is a complex interconnected web, and it is very hard to make changes to just one mechanism in isolation, so as to establish exactly its contribution. Now that biotechnology has advanced to the point at which near every biological mechanism is a viable target for intervention, it matters whether or not the research and development communities focus on the right targets, those that can produce meaningful benefits to patients.

Correlations are observed between the state of the gut microbiome and late life health, and the gut microbiome changes with age in ways thought to provoke inflammation and reduce the generation of beneficial metabolites. In today's open access paper, researchers propose that generation of excessive oxidative molecules via activities of the gut microbiome is an important factor in the onset and progression of age-related frailty.

It is almost certainly the case that the mechanisms described in the paper exist, but it is very hard to say how important they are in humans versus other layered and interacting issues in aging, such as chronic inflammation, or loss of stem cell function in muscle tissue, or immunosenescence. One way forward would be to perform fecal microbiota transplants in old people, using young donors, an approach shown to rejuvenate the gut microbiome in animal studies, but even this would mix in effects on inflammation and tissue function. It is challenging to make isolated changes in the body.

Oxidative stress bridges the gut microbiota and the occurrence of frailty syndrome

Frailty is one of the most complicated clinical syndromes and is defined as a decrease in the reserve and restoring capacity of the body. For frail people, a slight irritant can result in strong responses, which require a longer period to recover. Thus, frailty can also be regarded as a decline in the ability to maintain homeostasis. Multiple organs and systems, such as the skeletal muscle, immune, endocrine, hematopoiesis, and cardiovascular systems, are involved in the process of frailty. Patients with frailty have a high risk of developing age-related diseases, including neurodegenerative diseases (such as dementia), type II diabetes, atherosclerosis, and chronic heart failure.

Although there are a few hypotheses at present, the mechanisms involved in frailty remain unknown. Researchers have different opinions about the origin of frailty. It is generally accepted that frailty is related to aging. With the increasing focus on frailty, emerging evidence has increased our understanding of this syndrome. Findings from centenarians suggest that specific gut microbiota (GM) constituents may contribute to healthy aging. The diversity and abundance of the GM vary between elderly adults and centenarians.

However, the bridge between the GM and the occurrence of frailty remains unclear. In this review, we proposed the possible mechanisms involved in frailty from the perspective of the GM and oxidative stress (OS). Specific GMs and their metabolites stimulate the production of ROS and affect OS in the body, leading to damage to multiple biological macromolecules. The occurrence of OS may be the intermediate process of the GM that leads to frailty, producing a direct action on the body. This may be one of the precipitating factors of frailty syndrome.

The idea of using GM biomarkers to predict frailty is proposed prospectively. Notably, frailty is not an irreversible status. Timely interventions have the potential to revert the prefrailty or frailty state to a nonfrailty state. By understanding the role of the GM and OS in frailty, several interventions have been proposed to improve this syndrome and to achieve the goal of healthy aging. According to existing research, dietary interventions are the most commonly used treatment for frailty.

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