Interesting new study from the Skeletal Muscle Journal (“The endogenous molecular clock orchestrates the temporal separation of substrate metabolism in skeletal muscle”) found a protein that has some responsibility for the aging of our muscles and that may be affected by how we manage our circadian rhythms.
Losing Muscle as We Age
You may already know that we lose muscle naturally as we age. We call that “sarcopenia.” Research has found that sarcopenia is due as much to lifestyle as sheer age, so that with strength training you can hold on to more muscle fiber as you age. Why does that matter? Because more muscle means better mobility, greater functional abilities, better hormone regulation, faster recoveries, and increased bone density as we age. It also means higher metabolism and hence, greater lean mass. However, what do we mean when we say “we lose muscle”? We mean our quick type muscle fibers (described variously as white, type 2, fast-twitch) transform into slow type muscle fibers (red, type 1, slow-twitch) by neighboring type 1 fibers innervating atrophied type 2 neighbors.
The Study’s Conclusions
Researchers knew the protein Bmal1 regulated the circadian feeding rhythm of muscle. Now they think it regulates the aging of muscle. The study looked at mice without Bmal1, which is known to be responsible for metabolic processes. They found two things:
- This protein affects the circadian rhythm of muscle metabolism (how and when the muscles feed).
- There is more transition from type 2 to type 1 fibers where this protein is absent.
The study focused on the circadian rhythm of the metabolic processes in muscle fiber. That is, there is a regular daily cycle to what muscle utilizes for energy. Muscle uses glucose–a carbohydrate–more when it’s actively feeding (during the day) and lipids–fatty acids–when fasting (when we’re sleeping). During the transition period from active to sleep (often described as an hour after our daily activity has stopped, though not specifically mentioned in this study), our muscles begin to store the glucose or lipids it gets rather than utilize them.
They extrapolate that Bmal1 is involved in the aging process and that we can control our aging to some extent by maintaining consistent sleep and eating routines — activities that, when absent, have been found in other studies to disrupt our circadian rhythms.
Here, we report that the intrinsic molecular clock regulates the timing of genes involved in substrate catabolic and anabolic processes in skeletal muscle. We have identified the mid-inactive period as the time of peak expression of genes involved in fatty-acid breakdown, possibly serving as the main energy source to skeletal muscle during the overnight fasting period. The temporal expression pattern of genes that regulate glycolysis and glycolytic flux into the Kreb’s cycle suggests a shift in substrate utilization during the early active period from lipids to carbohydrates, which has previously been documented in other muscle-specific Bmal1 knockout models .
Genes involved in glucose and lipid storage were observed as reaching peak expression toward the end of the active phase, where we predict excess energy is stored for usage during the postabsorptive phase. Expression analysis of time-course data from iMS-Bmal1−/− skeletal muscle revealed the differential expression of a number of key circadian metabolic genes in the absence of BMAL1. These finding suggests that the temporal regulation and circadian rhythmicity of these genes is directly downstream of the intrinsic skeletal muscle molecular clock mechanism.
Lastly, we observe a gene expression profile that is indicative of a glycolytic to oxidative fiber type shift with loss of Bmal1 in adult muscle tissue. These findings suggest a potential unidentified role of Bmal1 in the maintenance of fast-type muscle fibers, possibly via direct transcriptional regulation of glucose handling. It is widely reported that aging is associated with a selective loss of fast-type skeletal muscle fibers ,. In addition, aging is also associated with decreases in the robustness of the molecular clock ,. These observations raise the possibility that fast to slow fiber-type shifts may be a result of dampening of the molecular clock with age.