Microbiome-mediated therapies for aging and healthspan in marmosets
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PROJECT SUMMARY The number one complaint given by the elderly is not pain and discomfort, but rather the need for independence as a part of their quality of life. Independence and health are ultimately tied to disease progression and elderly resilience, which may be related to the ability to be stress resistant and to recover following disease onset. The focus of aging research has now shifted to treating aging as a systemic problem, and determining whether an increase in lifespan alters the ability for that individual to remain disease free. The hope is that the treatment for multiple age-related diseases including diabetes, cardiovascular disease, Alzheimer's disease, dementia, and sarcopenia could be discovered by understanding mechanisms that underlie the basic systemic aging process. One potentially unexplored mechanism for age-related changes is the alteration of the intestinal microbiome. Dysbiosis of the microbiome has been associated with Type 2 diabetes, obesity, cardiovascular disease, frailty, aging, and Alzheimer's disease in human populations and may in fact be associated with the aging process. Unfortunately, evaluating dysbiosis in aging human populations is confounded by changes in dietary intake, exposure to pharmaceuticals, and alterations in physical activity. We hypothesize that loss of microbial diversity is significantly associated with the aging process and seek to evaluate these changes in a nonhuman primate model, the common marmoset. Further, we hypothesize that oral fecal microbiota transplants may be a potential therapeutic for stabilizing the aging microbiome and increasing healthspan maintenance. The proposed studies will evaluate the stability of the microbial diversity and function in aging marmosets, and the associated changes in measures of health. Fecal microbiota transplant will be conducted in aged marmosets and longitudinal assessment of microbial diversity and health will allow us to evaluate the efficacy of this treatment as an intervention for human healthspan.
