Much More than Just Loss of Mass is Involved in the Age-Related Decline of Muscle Function
It has been some years since sarcopenia was coined as a name for the characteristic loss of muscle mass and strength that occurs with aging, one of many attempts - some successful - to carve off an aspect of aging and obtain regulatory approval to work on treating it. It remains the case that making an official disease of sarcopenia is an ongoing process of lobbying with no end in sight, however. Without that blessing of the state there is no legal path to the translation of promising research into commercial clinical treatments, and thus far less incentive for the major funding sources to invest in any of the research needed to even get to the point at which commercial development is plausible.
In countries like the US only treatments for one of a list of defined diseases are considered for approval by the FDA, very much a case of all that is not permitted is forbidden. Even if sound and proven treatments exist and are widely used elsewhere in the world, people can be ruined financially and potentially go to jail for a long time for offering those treatments in the US. This was the case for first generation stem cell therapies for quite a number of years, for example. One of the large problems for the near future of longevity science as a whole is that aging itself is not considered a medical condition by the FDA and similar regulatory bodies. For so long as that is the case all meaningful early clinical development must occur in other regions of the world, and more importantly there will continue to be far less funding for research than might otherwise be the case.
Back to sarcopenia, however. There is indeed loss of muscle mass in aging, and this is a major cause of the frailty of later life. There is much more to the underlying processes than just a simple loss of mass, however. It is much more complex than that, as this review notes. The quoted portions are from the introduction and summary, and in between there is a more detailed overview of some of the mechanisms mentioned - it makes for interesting reading within the context that the practice of calorie restriction slows the progression of sarcopenia.
Worldwide estimates predict 2 billion people will be aged over 65 years by 2050. A major current challenge is maintaining mobility and quality of life into old age. Impaired mobility is often a precursor of functional decline, disability and loss of independence. Sarcopenia which represents the age-related decline in muscle mass is a well-established factor associated with mobility limitations in older adults. However, there is now evidence that not only changes in muscle mass but other factors underpinning muscle quality including composition, metabolism, aerobic capacity, insulin resistance, fat infiltration, fibrosis and neural activation may also play a role in the decline in muscle function and impaired mobility associated with ageing. Importantly, changes in muscle quality may precede loss of muscle mass and therefore provide new opportunities for the assessment of muscle quality particularly in middle-aged adults who could benefit from interventions to improve muscle function.Several longitudinal studies suggest that muscle mass alone cannot fully explain the loss of muscle strength and physical function in older adults. Estimates of the rate of change in muscle strength with age derived from a cross-sectional cohort have also been suggested to underestimate actual yearly changes in muscle strength. In the Health, Ageing, and Body Composition (Health ABC) study, the decline in muscle strength during ageing was reported to be two- to five fold greater than the loss of muscle mass in older adults aged 70-79 years over a 3-year follow-up period. Furthermore, there was wide inter-individual variability in changes in muscle cross-sectional area and muscle strength in older adults, such that muscle mass and muscle strength were well-preserved in some individuals but not others.
It will be important in future to better understand the main factors which underpin changes in muscle quality with age, which may well precede changes in muscle mass or be of greater functional significance in ageing muscles, with declining size. In addition, a universal consensus definition of muscle quality is necessary. Muscle quality is typically used to describe muscle strength or power per unit of muscle mass, therefore does not encompass muscle aerobic capacity which is closely associated with mobility and important for activities of daily living. Currently, there is a large gap in our knowledge on the primary determinants of muscle quality in middle-aged adults. The development of muscle quality assessment tools that encompass muscle quality and which are sensitive to small changes within muscle that precede a decline in muscle function would enable individuals to take preventative steps to maintain healthy muscle.