09.2018 | THE SCIENTIST 55© ISTOCK.COM, ALVAREZ; ©
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MUSCLED UP: In mice, it’s not just the brain that influences recovery from
a night of poor sleep.FEEL THE BURN: While exercise helps build muscle even as we age, it
does little for cells’ mitochondrial redox imbalance.CELL & MOLECULAR BIOLOGYPower Nap
THE PAPER
J.C. Ehlen et al., “Bmal1 function in skeletal muscle regulates sleep,”
eLife, 6:e26557, 2 0 1 7.UPSIDE DOWN
The protein Bmal1, which helps regulate the body’s internal clock, is
found in especially high levels in the brain and in skeletal muscles.
Mice completely deficient in Bmal1 were known to suffer from sleep
impairments, but the specifics at play weren’t clear. At the Univer-
sity of California, Los Angeles, Ketema Paul and colleagues looked to
these mice for clues about the role Bmal1 plays in sleep regulation.MUSCLE PL AY
When Paul’s team restored levels of the Bmal1 protein in the
mice’s brains, their ability to rebound from a night of bad sleep
remained poor. However, turning on production in skeletal muscles
alone enabled mice to sleep longer and more deeply to recover
after sleep loss.SWEET DREAMS
For decades, scientists have thought sleep was controlled purely
by the brain. But the new study indicates the ability to catch up on
one’s sleep after a bout of sleeplessness is locked away in skeletal
muscles, not the brain—at least for mice. “I think it’s a real paradigm
shift for how we think about sleep,” says John Hogenesch, a chrono-
biologist at Cincinnati Children’s Hospital Medical Center who dis-
covered the Bmal1 gene but was not involved in this study.TARG ET LOCKED
Paul’s group also found that having too much of the Bmal1 protein
in their muscles not only made mice vigilant but also invulnerable
to the effects of sleep loss, so that they remained alert even when
sleep-deprived and slept fewer hours to regain lost sleep. “ To me,
that presents a potential target where you could treat sleep disor-
ders,” says Paul, noting that an inability to recover from sleep loss
can make us more susceptible to diseases.
—Sukanya CharuchandraCELL & MOLECULAR BIOLOGYOld and Stressed Out
THE PAPER
G. P. Holloway et al., “Age-associated impairments in mitochondrial
ADP sensitivity contribute to redox stress in senescent human skele-
tal muscle,” Cell Rep, 22:2837–48, 2018.TOO MUCH OF A GOOD THING
The electron transport chain within mitochondria helps produce energy
in the form of AT P through redox reactions, generating reactive oxygen
species (ROS) in the process. In rodents, rising levels of ROS have been
linked to aging in mice, Graham Holloway of the University of Guelph in
Canada notes. In a recent study, his team used biopsies from a quadriceps
muscle to test whether the association held up in humans.LATERAL THINKING
The researchers grew human muscle fibers from biopsies in culture
in the presence of varying amounts of the AT P precursor ADP and
measured the amounts of oxygen used up and hydrogen peroxide
(an ROS) released in mitochondria.GROWING OLD
In healthy young adults, optimally functioning ADP ferries electrons
quickly through the final step of cellular respiration, meaning fewer
electrons can slip away to form ROS. Holloway’s group recorded
higher amounts of hydrogen peroxide in the muscle fibers from older
people (age ~70) at lower levels of A D P, indicating that the fibers had
become less sensitive to the molecule. “The paper has systemati-
cally shown how mitochondrial function and bioenergetics is greatly
affected during aging,” writes Jin Han, who studies energy metab-
olism at Inje University in South Korea but was not involved in this
study, in an email to The Scientist.LITTLE HELP
When Holloway and his colleagues tried the same experiment in
biopsies from older individuals undergoing resistance training at
the gym, the muscle fibers were in better health—stronger, leaner,
and more sensitive to A D P. But the skewed levels of peroxide
emission remained unchanged. —Sukanya Charuchandra