Abstract Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. Although the development of modern medicine has promoted human health and greatly extended life expectancy, with the aging of society, a variety of chronic diseases have gradually become the most important causes of disability and death in elderly individuals. Current research on aging focuses on elucidating how various endogenous and exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss of proteostasis, compromise of autophagy, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing) participate in the regulation of aging. Furthermore, thorough research on the pathogenesis of aging to identify interventions that promote health and longevity (such as caloric restriction, microbiota transplantation, and nutritional intervention) and clinical treatment methods for aging-related diseases (depletion of senescent cells, stem cell therapy, antioxidative and anti-inflammatory treatments, and hormone replacement therapy) could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity. 

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Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

ABSTRACT Alterations in the gut microbiota composition have been associated with a range of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders. The gut microbes transform and metabolize dietary- and host-derived molecules generating a diverse group of metabolites with local and systemic effects. The bi-directional communication between brain and the microbes residing in the gut, the so-called gut–brain axis, consists of a network of immunological, neuronal, and endocrine signaling pathways. Although the full variety of mechanisms of the gut–brain crosstalk is yet to be established, the existing data demonstrates that a single metabolite or its derivatives are likely among the key inductors within the gut–brain axis communication. However, more research is needed to understand the molecular mechanisms underlying how gut microbiota associated metabolites alter brain functions, and to examine if different interventional approaches targeting the gut microbiota could be used in prevention and treatment of neurological disorders, as reviewed herein. Abbreviations:4-EPS 4-ethylphenylsulfate; 5-AVA(B) 5-aminovaleric acid (betaine); Aβ Amyloid beta protein; AhR Aryl hydrocarbon receptor; ASD Autism spectrum disorder; BBB Blood–brain barrier; BDNF Brain-derived neurotrophic factor; CNS Central nervous system; GABA ɣ-aminobutyric acid; GF Germ-free; MIA Maternal immune activation; SCFA Short-chain fatty acid; 3M-4-TMAB 3-methyl-4-(trimethylammonio)butanoate; 4-TMAP 4-(trimethylammonio)pentanoate; TMA(O) Trimethylamine(-N-oxide); TUDCA Tauroursodeoxycholic acid; ZO Zonula occludens proteins

Microbiota-derived metabolites as drivers of gut–brain communication

http://manuscript.elsevier.com/S0952791522000243/pdf/S0952791522000243.pdf

Gut microbiome-mediated regulation of neuroinflammation.

No organism can avoid the process of aging, which is often accompanied by chronic disease. The process of biological aging is driven by a series of interrelated mechanisms through different signal pathways, including oxidative stress, inflammatory states, autophagy and others. In addition, the intestinal microbiota play a key role in regulating oxidative stress of microglia, maintaining homeostasis of microglia and alleviating age-related diseases. Tea polyphenols can effectively regulate the composition of the intestinal microbiota. In recent years, the potential anti-aging benefits of tea polyphenols have attracted increasing attention because they can inhibit neuroinflammation and prevent degenerative effects in the brain. The interaction between human neurological function and the gut microbiota suggests that intervention with tea polyphenols is a possible way to alleviate brain-aging. Studies have been undertaken into the possible mechanisms underpinning the preventative effect of tea polyphenols on brain-aging mediated by the intestinal microbiota. Tea polyphenols may be regarded as potential neuroprotective substances which can act with high efficiency and low toxicity.

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Tea Polyphenols as Prospective Natural Attenuators of Brain Aging

https://doi.org/10.1016/j.conb.2022.102652

Microbiota-immune-brain interactions: A lifespan perspective

Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine

http://www.jidonline.org/article/S0022202X23007716/pdf

Antal Szalay

Papers

Gut microbiota drives age-related oxidative stress and mitochondrial damage in microglia via the metabolite N6-carboxymethyllysine

589 Patients with advanced melanoma who benefit from the addition of anti-CTLA-4 to anti-PD-1 have a distinct tumor microenvironment (TME)