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      Clinical Interventions in Aging (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on prevention and treatment of diseases in people over 65 years of age. Sign up for email alerts here.

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      Trimethylamine N-Oxide, a Gut Microbiota-Dependent Metabolite, is Associated with Frailty in Older Adults with Cardiovascular Disease

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          Our study aimed to explore the association between trimethylamine N-oxide and frailty in older adults with cardiovascular disease.

          Patients and Methods

          This cross-sectional study analyzed a total of 451 people aged 65 years or older who underwent comprehensive geriatric assessments. Frailty status was determined using a frailty index constructed with 48 variables according to the cumulative deficits model. Physical frailty and cognitive frailty were also assessed in detail. Fasting plasma TMAO was measured by mass spectrometry.

          Results

          The proportion of frail subjects was 29.9% (135/451). Plasma TMAO levels were significantly higher in frail patients than in nonfrail individuals (4.04 [2.84–7.01] vs 3.21 [2.13–5.03] µM; p<0.001). Elevated plasma TMAO levels were independently associated with the likelihood of frailty (OR 2.12, 95% CI 1.01–4.38, p=0.046). Dose–response analysis revealed a linear association between the TMAO concentration and the OR for frailty. A 2-unit increase in TMAO was independently correlated with physical frailty (OR 1.23, 95% CI 1.08–1.41, p for trend 0.002) and cognitive frailty (OR 1.21, 95% CI 1.01–1.45, p for trend 0.04).

          Conclusion

          Elevated circulating TMAO levels are independently associated with frailty among older adults with cardiovascular disease.

          Most cited references32

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          Prediction of Creatinine Clearance from Serum Creatinine

          A formula has been developed to predict creatinine clearance (C cr ) from serum creatinine (S cr ) in adult males: Ccr = (140 – age) (wt kg)/72 × S cr (mg/100ml) (15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18–92. Values for C cr were predicted by this formula and four other methods and the results compared with the means of two 24-hour C cr’s measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr·s of 0.83; on average, the difference between predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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            Gut microbiota and aging.

            The potential for the gut microbiota to affect health has a particular relevance for older individuals. This is because the microbiota may modulate aging-related changes in innate immunity, sarcopaenia, and cognitive function, all of which are elements of frailty. Both cell culture-dependent and -independent studies show that the gut microbiota of older people differs from that of younger adults. There is no chronological threshold or age at which the composition of the microbiota suddenly alters; rather, changes occur gradually with time. Our detailed analyses have separated the microbiota into groups associated with age, long-term residential care, habitual diet, and degree of retention of a core microbiome. We are beginning to understand how these groups change with aging and how they relate to clinical phenotypes. These data provide a framework for analyzing microbiota-health associations, distinguishing correlation from causation, identifying microbiota interaction with physiological aging processes, and developing microbiota-based health surveillance for older adults.
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              Meta’omic analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism

              The human gut microbiome is linked to many states of human health and disease. 1 The metabolic repertoire of the gut microbiome is vast, but the health implications of these bacterial pathways are poorly understood. In this study, we identify a link between members of the genus Veillonella and exercise performance. We observed an increase Veillonella relative abundance in marathon runners post-marathon and isolated a strain of Veillonella atypica from stool samples. Inoculation of this strain into mice significantly increased exhaustive treadmill runtime. Veillonella utilize lactate as their sole carbon source, which prompted us to perform shotgun metagenomic analysis in a cohort of elite athletes, finding that every gene in a major pathway metabolizing lactate to propionate is at higher relative abundance post-exercise. Using 13C3-labeled lactate in mice we demonstrate that serum lactate crosses the epithelial barrier into the lumen of the gut. We also show that intrarectal instillation of propionate is sufficient to reproduce the increased treadmill runtime performance observed with V. atypica gavage. Taken together, these studies reveal that V. atypica improves runtime via its metabolic conversion of exercise-induced lactate into propionate, thereby identifying a natural, microbiome-encoded enzymatic process that enhances athletic performance.
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                Author and article information

                Journal
                Clin Interv Aging
                Clin Interv Aging
                cia
                clinintag
                Clinical Interventions in Aging
                Dove
                1176-9092
                1178-1998
                30 September 2020
                2020
                : 15
                : 1809-1820
                Affiliations
                [1 ]Department of Cardiology, Beijing Hospital, National Center of Gerontology , Beijing, People’s Republic of China
                [2 ]Chinese Academy of Medical Sciences, Peking Union Medical College , Beijing, People’s Republic of China
                Author notes
                Correspondence: Hua Wang; Jie-Fu Yang Department of Cardiology, Beijing Hospital, National Center of Gerontology , No. 1, Dahua Road, Dongcheng District, Beijing100730, People’s Republic of ChinaTel +86 13911680467; +86 13601292259Fax +86 10-58115035 Email wanghua2764@bjhmoh.cn; yangjiefu2011@126.com
                Author information
                http://orcid.org/0000-0002-4815-4055
                Article
                270887
                10.2147/CIA.S270887
                7534046
                33061331
                b3e22cfc-9d7e-4e06-886f-6393e9a98857
                © 2020 He et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 10 July 2020
                : 01 September 2020
                Page count
                Figures: 4, Tables: 6, References: 43, Pages: 12
                Funding
                Funded by: the Beijing Municipal Science & Technology Commission;
                Funded by: the CAMS Innovation Fund for Medical Sciences;
                Funded by: the Chinese Academy of Medical Sciences;
                Categories
                Original Research

                Health & Social care
                older adults,frailty,tmao,cardiovascular disease,physical frailty,cognitive frailty

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