Humans' indigenous microbes strongly influence organ functions in an age- and diet-dependent manner, adding an important dimension to aging biology that remains poorly understood. Although age-related differences in the gut microbiota composition correlate with age-related loss of organ function and diseases, including inflammation and frailty, variation exists among the elderly, especially centenarians and people living in areas of extreme longevity. Studies using short-lived as well as nonsenescent model organisms provide surprising functional insights into factors affecting aging and implicate attenuating effects of microbes as well as a crucial role for certain transcription factors like forkhead box O. The unexpected beneficial effects of microbes on aged animals imply an even more complex interplay between the gut microbiome and the host. The microbiome constitutes the major interface between humans and the environment, is influenced by biosocial stressors and behaviors, and mediates effects on health and aging processes, while being moderated by sex and developmental stages.
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