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      The gut microbiome as a modulator of healthy ageing

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          Abstract

          The gut microbiome is a contributory factor in ageing-related health loss and in several non-communicable diseases in all age groups. Some age-linked and disease-linked compositional and functional changes overlap, while others are distinct. In this Review, we explore targeted studies of the gut microbiome of older individuals and general cohort studies across geographically distinct populations. We also address the promise of the targeted restoration of microorganisms associated with healthier ageing.

          Abstract

          In this Review, O’Toole and colleagues discuss the composition and function of the gut microbiome as it relates to ageing and ‘unhealthy’ ageing as well as the potential for microbiome-directed interventions to encourage ‘healthy’ ageing.

          Key points

          • The gut microbiome is a transducer of environmental signals, modifies the risk of disease across all age groups and changes with host age.

          • Age-related alterations in the gut microbiome are influenced by personal factors, including progressive physiological deterioration, as well as by lifestyle-linked factors such as diet, medication and reduced social contact.

          • Age-related and disease-related deterioration in the gut microbiome of older people reflect overlapping interactive but distinct processes.

          • Resetting gut microbiome-derived signals of ‘unhealthy’ ageing through personalized or subpopulation-level microbiome-associated interventions is a new area of research informed by large shotgun metagenomics-based studies and data analytics.

          • Gut microbiome-based therapeutics for older people will need combined approaches, including dietary intervention with microbial restoration of lost strains.

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          Most cited references204

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            The Microbiota-Gut-Brain Axis

            The importance of the gut-brain axis in maintaining homeostasis has long been appreciated. However, the past 15 yr have seen the emergence of the microbiota (the trillions of microorganisms within and on our bodies) as one of the key regulators of gut-brain function and has led to the appreciation of the importance of a distinct microbiota-gut-brain axis. This axis is gaining ever more traction in fields investigating the biological and physiological basis of psychiatric, neurodevelopmental, age-related, and neurodegenerative disorders. The microbiota and the brain communicate with each other via various routes including the immune system, tryptophan metabolism, the vagus nerve and the enteric nervous system, involving microbial metabolites such as short-chain fatty acids, branched chain amino acids, and peptidoglycans. Many factors can influence microbiota composition in early life, including infection, mode of birth delivery, use of antibiotic medications, the nature of nutritional provision, environmental stressors, and host genetics. At the other extreme of life, microbial diversity diminishes with aging. Stress, in particular, can significantly impact the microbiota-gut-brain axis at all stages of life. Much recent work has implicated the gut microbiota in many conditions including autism, anxiety, obesity, schizophrenia, Parkinson’s disease, and Alzheimer’s disease. Animal models have been paramount in linking the regulation of fundamental neural processes, such as neurogenesis and myelination, to microbiome activation of microglia. Moreover, translational human studies are ongoing and will greatly enhance the field. Future studies will focus on understanding the mechanisms underlying the microbiota-gut-brain axis and attempt to elucidate microbial-based intervention and therapeutic strategies for neuropsychiatric disorders.
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              The Human Intestinal Microbiome in Health and Disease.

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                Author and article information

                Contributors
                pwotoole@ucc.ie
                Journal
                Nat Rev Gastroenterol Hepatol
                Nat Rev Gastroenterol Hepatol
                Nature Reviews. Gastroenterology & Hepatology
                Nature Publishing Group UK (London )
                1759-5045
                1759-5053
                25 April 2022
                : 1-20
                Affiliations
                [1 ]GRID grid.7872.a, ISNI 0000000123318773, APC Microbiome Ireland, , University College Cork, National University of Ireland, ; Cork, Ireland
                [2 ]GRID grid.7872.a, ISNI 0000000123318773, School of Microbiology, , University College Cork, National University of Ireland, ; Cork, Ireland
                [3 ]GRID grid.7872.a, ISNI 0000000123318773, Department of Medicine, , University College Cork, National University of Ireland, ; Cork, Ireland
                Author information
                http://orcid.org/0000-0001-9570-0365
                http://orcid.org/0000-0003-0467-0936
                http://orcid.org/0000-0001-5377-0824
                Article
                605
                10.1038/s41575-022-00605-x
                9035980
                35468952
                c0ce1afd-9c76-41bd-b88b-f75d41cb05ba
                © Springer Nature Limited 2022

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 9 March 2022
                Categories
                Review Article

                microbiota,microbiome
                microbiota, microbiome

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