Fight Aging!

The authors of this open access review walk through some of the evidence for delivery of exosomes, such as those derived from stem cells, to be a basis for treating sarcopenia. Sarcopenia is the progressive loss of muscle mass and strength that takes place with aging. While a fair degree of sarcopenia is preventable, being the consequence of an age of comfort, leisure, and too little exercise, the rest of it is still inevitable absent some way to interfere in the mechanisms of aging that disrupt muscle tissue maintenance. The delivery of cell signals encapsulated in exosomes might be capable of forcing muscle stem cells into greater activity, overriding their natural reaction to an aged tissue environment. While this class of therapy doesn't address the underlying causes of the problem, the benefits may still be large enough to be worth chasing.

Sarcopenia is one of the hallmarks of the aging process. Human muscle undergoes constant changes with the most alterations taking place with age. As shown by different studies, on average, the prevalence of sarcopenia in older adults aged 60-70 years lies at 5-13%, increasing to 11-50% in people aged 80 or older. Sarcopenia is closely related to negative outcomes in older adults, such as an increased risk of falls and fractures and impaired cognitive function and physical performance. Researchers estimated that the economic costs for sarcopenia in the USA were about $18.5bn in 2000. Strikingly, if the prevalence of sarcopenia would be reduced by only 10%, it would save $1.1bn in medical costs per year in the US health care expenditures. Therefore, it is urgent to develop more effective research strategies and therapeutic approaches for preventing sarcopenia based on a better understanding of the potential mechanisms of this disease.

Over the years, many researches have investigated physiological and pathological conditions related to poor muscle regeneration in sarcopenia. However, the underlying molecular mechanisms associated with sarcopenia remain not completely understood. Some evidence suggests that such factors as anabolic resistance and endothelial dysfunction may contribute to the development of sarcopenia. Another one of the recent studies reported that exosomes released by muscles into the bloodstream may also play an essential role in muscle regeneration. This opens a novel field of research in preventing muscle loss. It is hypothesized that exosomes as carrier of a cargo of proteins, mRNA, miRNA, and other non-coding RNAs play a crucial role in myogenesis and muscle development. It has been shown in a mouse model of muscle injury that human skeletal myoblasts-derived exosomes containing all sorts of signal molecules can promote muscle regeneration.

Although the treatment of sarcopenia remains challenging, it is widely accepted that such strategies as nutritional supplementation and physical training (both aerobic exercise and resistance exercise) are the key interventions that can help maintain skeletal muscle mass. However, the molecular mechanisms behind the prevention from the age-related muscle loss by nutrition and exercise are still poorly understood. More recent data indicate that exercise attenuates sarcopenia mainly through increasing peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) signalling, which can be activated by heat shock protein 60-bearing exosomes released after physical training. This connection between sports and release of exosomes supports the assumption about the key role of exosomes in muscle regeneration.

Other recent data also indicates that exosomes, secreted by skeletal muscle cells and carrying miRNAs and other factors, may act as vital modulators of skeletal muscle function, and may have the potential in the research strategies of sarcopenia. Owing to their diverse pathological and therapeutic effects, exosomes has attracted more attention in the scientific community in recent years. It has been shown that exosomes are related to organ crosstalk and can be beneficial in research of many diseases, including kidney injury, myocardial infarction, Parkinson's disease, and cancer. Importantly, the present data suggest that exosomes may mediate and enhance the beneficial effects of exercise. Emerging evidence has presented that exosomes as carriers can increase muscle regeneration after skeletal muscle injury and improve muscle protein synthesis and hypertrophy, which could support exosomes as vectors for future research strategies of sarcopenia. All these mechanisms are interconnected, but the underlying pathways are still not understood completely and should be examined more thoroughly in future studies.

Link: https://doi.org/10.1002/jcsm.12536