Gut microbiota: A player in aging and a target for anti-aging intervention

Vaiserman, Alexander; Koliada, Alexander; Marotta, Francesco

doi:10.1016/j.arr.2017.01.001

Cited by 372 publications

(266 citation statements)

References 121 publications

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“…This led to a decrease in the overall degree of microbial translocation and ultimately improved immune cell function (Gori et al., 2011). The microbial communities of the elderly gut appear to be strongly influenced by diet (Claesson et al., 2012), and dietary interventions designed to restore a robust microbiota may improve anti-bacterial immunity by reducing age-associated inflammation and macrophage immunosenescence (Clements and Carding, 2016, Vaiserman et al., 2017). …”

Section: Discussionmentioning

confidence: 99%

Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction

Thevaranjan

Puchta

Schulz

et al. 2017

Cell Host & Microbe

905

672

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SummaryLevels of inflammatory mediators in circulation are known to increase with age, but the underlying cause of this age-associated inflammation is debated. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to 600 days than their conventional counterparts, and macrophages derived from aged germ-free mice maintain anti-microbial activity. Co-housing germ-free mice with old, but not young, conventionally raised mice increases pro-inflammatory cytokines in the blood. In tumor necrosis factor (TNF)-deficient mice, which are protected from age-associated inflammation, age-related microbiota changes are not observed. Furthermore, age-associated microbiota changes can be reversed by reducing TNF using anti-TNF therapy. These data suggest that aging-associated microbiota promote inflammation and that reversing these age-related microbiota changes represents a potential strategy for reducing age-associated inflammation and the accompanying morbidity.

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Section: Discussionmentioning

confidence: 99%

Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction

Thevaranjan

Puchta

Schulz

et al. 2017

Cell Host & Microbe

905

672

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“…Changes of gut microbiota composition, called dysbiosis, may lead to higher levels of TMAO (Kitai et al, 2016). Aging process has been shown to induce alterations in composition, diversity and functional features of gut microbiota, which are associated with aging-related decline in immune system functioning and chronic inflammation (Vaiserman et al, 2017). In the present study, we found that old control animals had significantly higher levels of plasma TMAO than young control animals, indicating that aging process elevates circulating TMAO levels.…”

Section: Discussionmentioning

confidence: 99%

Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress

et al. 2017

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Vascular endothelial dysfunction, a characteristic of the aging process, is an important risk factor for cardiovascular disease in aging. Although, vascular inflammation and oxidative stress are major contributors to endothelial dysfunction in aging, the underlying mechanisms during the aging process are not fully understood. Accumulating evidence reveals that gut microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) is implicated in the pathogenesis of many cardiovascular diseases. We tested the hypothesis that aging increases circulating TMAO levels, which induce vascular inflammation and oxidative stress, resulting in age-associated endothelial dysfunction. Old (22-mo-old) and young (4-mo-old) Fischer-344 rats were treated without (control) or with 1.0% 3,3-Dimethyl-1-butanol (DMB, an inhibitor of trimethylamine formation) in drinking water for 8 weeks. Compared with young control group, old control group had markedly higher plasma TMAO levels, which were reduced by DMB treatment. Endothelium-dependent relaxation of aorta in response to acetylcholine was impaired in old control group compared with young control group as indicated by decreased maximal relaxation (Emax) and reduced area under the curve (AUC). Emax and AUC were both normalized in old rats treated with DMB. No difference in endothelial-independent relaxation in response to sodium nitroprusside was observed among groups. Molecular studies revealed that old control group exhibits increased expression of proinflammatory cytokines and superoxide production, and decreased expression of endothelial nitric-oxide synthase (eNOS) in the aorta, all of which were restored by DMB treatment. These results suggest that aging increases circulating TMAO levels, which may impair eNOS-derived NO bioavailability by increasing vascular inflammation and oxidative stress, contributing to aging-associated endothelial dysfunction.

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“…During aging, gut microbiota composition physiologically faces reduced species richness and increased interindividual variability 26. In 2012, Claesson et al demonstrated that these alterations are particularly observed in older subjects with physical frailty and living in nursing home, partly because of reduced mobility and variety in dietary habits 27…”

Section: Introductionmentioning

confidence: 99%

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

Ticinesi¹,

Tana²,

Nouvenne³

et al. 2018

CIA

168

133

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Cognitive frailty, defined as the coexistence of mild cognitive impairment symptoms and physical frailty phenotype in older persons, is increasingly considered the main geriatric condition predisposing to dementia. Recent studies have demonstrated that gut microbiota may be involved in frailty physiopathology by promoting chronic inflammation and anabolic resistance. The contribution of gut microbiota to the development of cognitive impairment and dementia is less defined, even though the concept of “gut–brain axis” has been well demonstrated for other neuropsychiatric disorders. The aim of this systematic review was to summarize the current state-of-the-art literature on the gut microbiota alterations associated with cognitive frailty, mild cognitive impairment and dementia and elucidate the effects of pre- or probiotic administration on cognitive symptom modulation in animal models of aging and human beings. We identified 47 papers with original data (31 from animal studies and 16 from human studies) suitable for inclusion according to our aims. We concluded that several observational and intervention studies performed in animal models of dementia (mainly Alzheimer’s disease) support the concept of a gut–brain regulation of cognitive symptoms. Modulation of vagal activity and bacterial synthesis of substances active on host neural metabolism, inflammation and amyloid deposition are the main mechanisms involved in this physiopathologic link. Conversely, there is a substantial lack of human data, both from observational and intervention studies, preventing to formulate any clinical recommendation on this topic. Gut microbiota modulation of cognitive function represents, however, a promising area of research for identifying novel preventive and treatment strategies against dementia.

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Gut microbiota: A player in aging and a target for anti-aging intervention

Cited by 372 publications

References 121 publications

Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction

Age-Associated Microbial Dysbiosis Promotes Intestinal Permeability, Systemic Inflammation, and Macrophage Dysfunction

Elevated Circulating Trimethylamine N-Oxide Levels Contribute to Endothelial Dysfunction in Aged Rats through Vascular Inflammation and Oxidative Stress

Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review

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