Fight Aging!

The gut microbiome is a highly varied collection of microbial populations that acts in symbiosis with the body to process food and provide needed metabolites. With age, there is a detrimental shift in these populations. Those generating useful metabolites, such as butyrate, diminish in number. Those capable of infiltrating tissue, generating inflammatory compounds, or otherwise interacting with the immune system to provoke chronic inflammation increase in number. Researchers have demonstrated that this is a meaningful process in short-lived species by transplanting a youthful gut microbiome into older individuals. In killifish, for example, this produces extension of life. In mice, it has been shown to beneficially change measures of metabolic aging. In aged humans, better health at a given age corresponds to a younger gut microbiome configuration.

In today's open access review paper, researchers look at just one set of processes that may be influenced by the gut microbiome, those contributing to age-related anabolic resistance. Muscle growth depends on anabolism - the construction of proteins needed for cellular structures, new cells, and tissue mass - and an aged body does not produce the same level of anabolic response to stimuli such as exercise or increased protein intake. This leads to sarcopenia, the characteristic, steady loss of muscle mass over the years. Why does anabolic resistance arise with age? It is proposed that the changing populations of the gut microbiome play a role, though as is usually the case in aging, assigning a relative importance to different processes is considerably harder than identifying those processes in the first place.

Evidence for the Contribution of Gut Microbiota to Age-Related Anabolic Resistance

The aging process is associated with pervasive physiological declines that are exemplified by reductions in size and function of skeletal muscle (i.e., sarcopenia). Given the association between sarcopenia with adverse health outcomes (e.g., falls, fractures, and mobility limitations) and mortality, a more definitive understanding of the biological mechanisms underlying sarcopenia is warranted.

The regulation of skeletal muscle mass is dictated by temporal fluctuations in muscle protein synthesis (MPS) and muscle protein breakdown (MPB). Though the effect of aging on whole body protein turnover was initially a subject of great contention, it is now generally accepted that healthy aging is not accompanied by accelerated MPB. Furthermore, comparable rates of basal MPS and turnover have been observed in healthy older and younger adults. However, in older animals and humans alike, the sensitivity of MPS to anabolic stimuli, such as protein feeding, is substantially diminished when compared with that in the young. This blunted anabolic responsiveness, termed anabolic resistance, is highly characteristic of aging skeletal muscle, and much effort is being devoted to delineating the etiology of this phenomenon. Greater insight into this area may help to optimize the rehabilitative role of protein intake for the maintenance and/or recovery of skeletal muscle tissue in older adults.

The gut microbiota refers to the collective of bacteria, archaea, viruses, and eukaryotic microbes that reside in the gastrointestinal tract. Though best known for its role in nutrient uptake, the gut microbiome is also intricately connected to a diverse array of physiological systems; influencing metabolic function, protecting against pathogens, and modulating immune response. Recent studies by several independent research groups have provided evidence for a bidirectional gut-muscle axis with profound implications for aging skeletal muscle and sarcopenia. As studies supporting a role for the gut microbiome in regulating muscle mass and function continue to accumulate, whether baseline microbial signatures may influence anabolic potential is deserving of deeper inquiry.

The purpose of this review will be to provide evidence in support of the hypothesis that age-associated changes in gut microbiota composition contribute to anabolic resistance following protein feeding in older adults that underlie sarcopenia. We will begin by outlining how changes in gut microbiota that are hallmarks of aging may impact protein digestion and amino acid absorption, reduce circulating amino acid availability, contribute to anabolic hormone deficiencies or impair responsiveness, and play a role in intramuscular signaling deficits - all of which may underlie age-related anabolic resistance.

A bidirectional gut-muscle axis with implications for aging skeletal muscle size, quality, and function has been proposed. Extending on this aging gut-muscle axis, we propose that age-related changes in gut microbiota may detract from the anabolic response of skeletal muscle to protein feeding in older adults. Intriguingly, many of these adverse microbial modifications seem to be avoided in long-lived models of highly successful aging. Through the above, we describe how commonly observed age-related changes in the gut microbiome may compromise anabolic responsiveness through their impact on protein digestion and amino acid absorption, circulating amino acid availability, anabolic hormone production and responsiveness, and anabolic intramuscular signaling.

While some of these age-associated gut microbiome alterations may simply be a product of the natural aging process, we believe that lifestyle modification (i.e., improved diet, exercise, sleep, and reducing medication use) may help to preserve gut microbial equilibrium in a manner that would be anticipated to maintain anabolic capacity in older years. To validate this hypothesis, interventional studies attempting to manipulate microbial ecology as a means to potentiate muscle protein synthetic responses to anabolic stimuli (i.e., protein feeding) in older individuals are needed.