09.2018 | THE SCIENTIST 53els comparable to those observed in young
subjects. Additionally, exercise improved
muscle function: the older adults were
59 percent weaker than the younger
adults before training, and only 38 per-
cent weaker afterward.^12 Different types
of exercise can trigger variable but spe-
cific responses in the muscle. For exam-
ple, whereas strength training is efficient
at making muscle, high intensity interval
training in aerobic exercises such as biking
and walking had the greatest effect at the
cellular level at combating age-related loss
and weakness, according to Nair’s work.
Exercise also appears to influence
autophagy. In December 2011, Sandri and
his colleagues were the first to report, in
mice, that autophagy activity could be
boosted by voluntary physical activity,
in this case, running on a treadmill.^13 In
January 2012, the team of Beth Levine
at the University of Texas Southwestern
Medical Center confirmed that exercise
rapidly increased autophagy activity and
that autophagy is required for exercise
to have its beneficial effects: physically
active mice that were unable to ramp up
autophagy did not show any increase in
muscle mass, mitochondrial content, or
insulin sensitivity after running.^14
Finally, exercise can also apparently
restore levels of myokines that decline
with age. For example, when elderly sub-
jects followed a regular program of physi-
cal activity, there was a direct correlation
between the improvement in their phys-
ical performance and the increase in the
level of circulating apelin.^15 Similarly, Ivan
Bautmans from Vrije Universiteit Brussel
showed that increased circulating levels of
inflammation markers correlate with mus-
cle fatigue in geriatric patients, and that
resistance training decreased inflamma-
tory myokines in young adults.^16
By these mechanisms and others we
have yet to discover, exercise can improve
overall strength in the elderly, and specifi-
cally, the metabolic vigor of skeletal mus-
cle. Being the most abundant tissue in
the average human body, accounting for30 percent to 40 percent of its total mass,
muscle is not only critical for locomotion
and breathing, but also for glucose, lipid,
and amino-acid homeostasis. The age-
associated loss of muscle mass and quality
thus contributes to the general metabolic
dysfunction commonly seen in elderly
patients. In older women, one hour of
brisk walking produced elevated insulin
sensitivity on the following d ay. There-
fore, it is never too late to exercise to try to
combat the consequences of muscle aging.
A detailed understanding of the
molecular and cellular pathways
involved in muscle aging could pave the
way for the development of therapeutic
interventions to boost protein synthesis
and increase muscle mass. For now, reg-
ular exercise combined with good nutri-
tion is still the most effective way to fight
sarcopenia, and possibly aging over-
all. In addition to detailing the under-
lying causes of muscle aging, future
research should seek to define optimal
physical exercise and nutritional pro-
grams to combat age-related muscle loss
and weakness. It may not significantly
increase human lifespan, but it will cer-
tainly help people reach the end of their
lifespan in a healthier condition. gGillian Butler-Browne studies neuromuscu-
lar diseases and gene therapy at Sorbonne
Université, INSERM, Institut de Myolo-
gie, Centre de Recherche en Myologie, in
Paris, France. At the same institution, Vin-
cent Mouly studies muscle regeneration in
health and disease, Anne Bigot studies mus-cle aging, and Capucine Trollet studies age-
related muscle disease and gene therapy.References- A. Mauro, “Satellite cell of skeletal muscle fibers,”
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Exercise may prevent or reverse many
of these age-related changes, whereas
inactivity will accelerate muscle aging.