Fight Aging!

In today's study, researchers report on a comparison between mice undergoing life-long exercise (a wheel in their cage) versus more sedentary mice (no wheel). The authors note that the age-related onset of sarcopenia is much reduced in the exercising mice, which we could perhaps take as more of an indication of the harms of a lack of exercise than of the benefits of exercise per se. This is perhaps the least interesting part of the data and discussion, however. One of the points being made by the researchers is that the effects of life-long exercise are underestimated by the research community, because this intervention is not well studied in either mice or humans, at least in comparison to shorter periods of exercise commencing in old age.

The other point being made is that while it is known that exercise helps to blunt the loss of capillary density with age, the markers that the researchers assessed for cellular biochemistry related to angiogenesis, the creation of blood vessels, are not telling a story that matches up with the observed outcome. Thus the present understanding of the way in which exercise interacts with maintenance of capillary networks over the long term is probably incomplete, and there are other pathways to discover and investigate.

Capillary density is important in the operation of energy-hungry tissues such as muscle and the brain, being the road by which nutrients reach cells. Fewer capillaries means a lesser supply of nutrients and a consequent stress on cells and loss of tissue function. This issue of capillary densitry is probably a useful point of intervention, given safe strategies to adjust the operation of angiogenesis, such as VEGF gene therapy or CXCL12 upregulation via small molecule drugs.

Effects of lifelong spontaneous exercise on skeletal muscle and angiogenesis in super-aged mice

The effect of endurance exercise on sarcopenia is underestimated compared to that of resistance exercise. The reason for this is that the studies so far have mainly focused on therapeutic approaches after the onset of sarcopenia. In addition, large-scale epidemiological studies are difficult to control for variables that directly or indirectly affect endurance exercise. In the case of clinical studies, it is difficult to obtain various physiological phenotypes in the muscles following endurance exercise through research because long-term endurance exercise intervention over a lifetime is virtually impossible.

Our previous study indirectly demonstrated that the risk of premature death can be lowered by maintaining energy homeostasis in super-aged mice subjected to lifelong spontaneous exercise (LSE). Therefore, it was expected that the onset of sarcopenia caused by aging would be delayed or the risk of sarcopenia occurring during aging would be lowered if LSE that mimics endurance exercise is performed. We aimed to investigate the quantity and quality of skeletal muscle in 25-month-old super-aged mice (99-week-old, corresponding to a human age of at least 70 years), which corresponds to the late life of naturally aging mice used as a rodent model for sarcopenia. In particular, one of the key points of this study was to explain capillary density (expression of angiogenesis-related genes and angiogenic capacity), which is known to be closely related to endurance exercise, by integrating the results of our previous study.

Our findings show that LSE could maintain skeletal muscle mass, quality, and fitness levels in super-aged mice. In addition, ex vivo experiments showed that the angiogenic capacity was maintained at a high level. However, these results were not consistent with the related changes in the expression of genes and/or proteins involved in protein synthesis or angiogenesis. Based on the results of previous studies, it seems certain that the expression at the molecular level does not represent the phenotypes of skeletal muscle and angiogenesis. This is because aging and long-term exercise are variables that can affect both protein synthesis and the expression patterns of angiogenesis-related genes and proteins. Therefore, in aging and exercise-related research, various physical fitness and angiogenesis variables and phenotypes should be analyzed.