Calorie Restriction Makes Old Muscle Metabolism More Youthful

The rudiments of rejuvenation treatments that will emerge in the 2020s and 2030s are presently under development at an early stage in the laboratory, largely with very limited funding and attention. It is true that those portions of the rejuvenation toolkit envisaged by the SENS Research Foundation that involve stem cells are far ahead of the pack in terms of the pace of development and the availability of first generation treatments. For the rest of it, however, all of the other varied technologies needed to repair the causes of degenerative aging, even where there are real and exciting signs of progress, as is the case for clearance of senescent cells, it will be years yet before the first reliable, partially effective treatments are available even via medical tourism.

It is a strange thing indeed for a basically healthy individual to stand in the midst of revolutionary progress in biotechnology, at a time when the research community is finally turning its attention to treating aging as a medical condition, and yet have few new tools available now to improve the odds of living a longer, healthy life. Today's middle-aged individuals can get stem cell treatments for their joints and have easy access to much more reliable data on the benefits of exercise and calorie restriction, but other than that they aren't all that much better off in comparison to their counterparts of half a century past. All of the diffuse advantages of fifty years of progress in medicine has provided perhaps five years of additional remaining life expectancy in middle age. When it comes to what you can choose to do here and now to make a difference in your long-term health the biggest tangible gains still emerge from regular moderate exercise and the practice of calorie restriction.

Calorie restriction has been shown to extend life in near all species examined, and in those where it is most examined, such as in mice, it has been demonstrated to slow near all measures of degenerative aging. Undertaking calorie restriction clearly doesn't have the same effect on maximum life span in humans as it does in mice - we'd have noticed centuries ago if restricting calories while maintaining good nutrition could reliably add decades to life spans. It does, however, improve all of the short term measures of health in humans to much the same considerable degree it does in shorter-lived species, provides resistance to age-related disease, and improves long-term health to a greater degree than any presently widely available medical technology. Will it give you good odds to living to see 90? No. Even today, three-quarters of the healthiest people die before reaching 90. What calorie restriction will do, however, is give you a better chance of living to benefit from the rejuvenation treatments of the future. In an age of rapid progress in medicine a year gained here or a year gained there can be a big deal.

Here is an example of the sort of benefits provided by calorie restriction, in this case with a focus on the metabolism of muscle tissues and the way in which it changes with age. Like many other studies, it demonstrates that it is never too late to start trying calorie restriction. You'll most likely be better off than if you chose not to:

Caloric Restriction: A Fountain of Youth for Aging Muscles?

Calorie restriction is thought to have a protective effect on muscle cells and may help cells better use antioxidants, avoid damage caused by free radicals and function better. While studies that observed the effects of lifelong calorie restriction have shown mixed results in animals of different ages, recent studies have suggested that age may play a role in how CR affects individual animals. The research team hypothesized that because CR can help reprogram metabolism, the most benefit can be reaped from aging muscles in which cellular metabolism is impaired.

Researchers focused on two pathways that produce energy in muscles, glycolysis (sugar metabolism) and mitochondrial oxidative phosphorylation (OXPHOS) in both young and middle-aged rats that were fed a normal diet or a calorie-restricted diet. In the 14-week study, rats on the calorie-restricted diet received 10 percent calorie restriction in the first week, 25 percent restriction in the second and 40 percent restriction for the remaining 12 weeks. The control rats received no calorie restriction. After 14 weeks, the researchers studied changes in the rats' muscles.

"We investigated whether CR reprogrammed muscle metabolism and whether this improvement was associated with the observed increase in muscle mass. In addition, we examined whether the CR-induced changes were age-dependent." Not surprisingly, the middle-aged rats had less muscle mass than the young rats did. However, while 14 weeks of calorie restriction did not significantly affect the middle-aged rats, it reduced muscle mass in the young rats. Calorie restriction slowed the glycolytic rate in the muscles and increased the cells' dependency for OXPHOS versus glycolysis in older rats, which was linked to improvement of normalized muscle mass. The team also found that "14 weeks of CR reprogrammed cellular metabolism, where the relative contribution of OXPHOS and glycolysis in muscles of middle-aged rats with CR was similar to that in muscles of young rats."

Late-onset Caloric Restriction Alters Skeletal Muscle Metabolism by Modulating Pyruvate Metabolism

Caloric restriction (CR) attenuates age-related muscle loss. However, the underlying mechanism responsible for this attenuation is not fully understood. This study evaluated the role of energy metabolism in the CR-induced attenuation of muscle loss. The aims of this study were two-fold: (1) to evaluate the effect of CR on energy metabolism and determine its relationship with muscle mass, and (2) to determine whether the effects of CR are age-dependent.

Young and middle-aged rats were randomized into either 40% CR or ad libitum (AL) diet groups for 14 weeks. Major energy-producing pathways in muscles, i.e., glycolysis and mitochondrial oxidative phosphorylation (OXPHOS), were examined. We found that the effects of CR were age-dependent. CR improved muscle metabolism and normalized muscle mass in middle-aged animals but not young animals. CR decreased glycolysis and increased the cellular dependency for OXPHOS versus glycolysis in muscles of middle-aged rats, which was associated with the improvement of normalized muscle mass.

The metabolic re-programming induced by CR was related to modulation of pyruvate metabolism and increased mitochondrial biogenesis. Compared to animals fed AL, middle-aged animals with CR had lower lactate dehydrogenase A content and greater mitochondrial pyruvate carrier content. In conclusion, 14 weeks of CR improved muscle metabolism and preserved muscle mass in middle-aged animals but not in young, developing animals. CR-attenuated age-related muscle loss is associated with reprogramming of the metabolic pathway from glycolysis to OXPHOS.

Comments

I read your blog and it triggers small, but semi-regular donations to SENS.

Posted by: Jersey Jones at April 23rd, 2015 8:58 AM

I was reading a paper yesterday that indicates that CR is linked to telomerase activation via a certain pathway. In other words CR induces activation of telomerase so ironically it has a small rejuvenating action. However far too much research time and effort is spent on CR and it will return little gain in terms of lifespan. Far better to get on with looking at robust interventions but of course that's not how the current system works...

Posted by: Steve H at April 24th, 2015 2:18 AM

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