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“But what happens in type 2 diabetes is still a remaining ques-

tion in humans.”

Muscle clocks may affect aspects of health other than metab-

olism as well. Esser and her colleagues have found that knock-

ing out tissue-specific timekeepers leads to weaker muscles in

mice.^11 Her team has also observed, in unpublished work, that

perturbing these clocks can influence the physiology of sarco-

meres, the basic units of muscle tissue. “When we disrupt the

clock, we’re starting to see variations in the length of the sarco-

mere along a single fiber,” Esser says. “[This can] affect force

generation, and the prediction is that you might make this mus-

cle more susceptible to injury.”

Muscle clocks can also influence rodents’ slumber. Neu-

roscientist Ketema Paul of the University of California, Los

Angeles, and his colleagues revealed that removing Bmal1

from the muscles of mice increased the amount of time the

rodents spent in non-REM sleep.^12 Moreover, the researchers

found that, while knocking out this gene in the brain or mus-

cles impaired the rodents’ ability to regain normal sleep pat-

terns after six hours of forced wakefulness, increasing Bmal1

expression in muscle made them better at bouncing back after

sleep deprivation. (See “Power Nap,” pg. 55.) In addition to pro-

viding a better understanding of the mechanisms that mediate

sleep homeostasis, Paul says, these findings hint at potential

treatments that target nonbrain tissues for sleep disorders or

improve recovery after sleep loss.

Many questions remain about the way muscle keeps time,

such as how external signals are incorporated. Studies, pri-

marily in rodents, suggest that feeding and exercise may serve

as primary environmental cues. Oxygen levels may also play a

MUSCLE TIME

The muscles’ intrinsic timekeepers keep

the body’s metabolic pathways in sync with

activity and rest cycles during the day.

The muscle clock is regulated by feeding

and physical activity—behaviors controlled

in part by the suprachiasmatic nucleus

(SCN), the body’s so-called master clock.

Researchers have found that the muscle’s

intrinsic rhythms could be tweaked in

mice by changing the timing of feeding

(Gene Dev, 14:2950–61, 2000), which is an

important cue for other peripheral clocks as

well. Scheduled exercise can also tune the

muscle’s clocks, affecting the expression

of circadian genes such as those involved

in maintaining the muscles’ contractile

properties (Med Sci Sports Exerc, 44:1663–70,

2012). Conversely, disrupting muscle clocks

can aff ect sleep, suggesting that rhythms in

the body’s peripheral tissues feedback on

the brain, possibly through circulating

hormones or other chemical messengers.

Master clock

(SCN)

Other

peripheral clocks

Muscle

clocks

infl uence

sleep

Muscle clock

Feeding Activity

Light

Glucose and lipid

metabolism

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