Exercise may be the best anti-ageing pill

19 Oct

NS 2990: Exercise may be the best anti-ageing pill
* 10 October 2014 by Clare Wilson

IT COULD be the biggest killer you’ve never
heard of: the weakening
and loss of muscle that happens as we get

Muscle loss is no longer seen as just a side
effect of disease and
frailty – it’s also a prime cause. As well as
contributing to falls,
muscle loss has serious knock-on effects
on metabolism (see
“Life-saving muscle”). In future, muscle-boosting drugs could aid
those unable to maintain muscle mass
through exercise such as weight
training. Although researchers stress this
isn’t about bodybuilding,
but keeping muscles in your limbs at a
healthy level.

Muscle loss, also known as sarcopenia, is
increasingly being seen as
an important facet of ageing, according to
several speakers at a
conference on longevity drugs held in
Basel, Switzerland, last
month. “Treatments will eventually get into
the market,” said Dan
Perry of the patient lobby group Alliance for
Aging Research.

However, the mechanisms behind muscle
ageing are still poorly
understood – although new research
suggests it involves damage from
free radicals.

Mice that have been genetically modified to
produce fewer free
radicals in their mitochondria are known to
live about 20 per cent
longer than normal mice. So a team led by
Andrew Marks at Columbia
University in New York investigated how
this affected the ageing of
their muscle tissue.

They found that a key player is calcium, the
release of which
triggers our muscles to contract. The
molecule responsible for this
release – ryanodine receptor 1 – is
damaged by free radicals, and as
the rodents age, calcium begins to leak out
when it shouldn’t,
weakening muscle fibres.

The modified mice experienced less free
radical damage to the
ryanodine receptor 1. They also had
stronger muscles, and, in old
age, chose to run on their exercise wheels
more than unmodified mice
– by about an extra kilometre a day (PNAS,

“It helps point to the role that mitochondria
play in the muscle
ageing process,” says Daniel Moore of the
University of Toronto,

Marks has founded a firm called Armgo to
develop several compounds
aimed at preventing calcium leakage,
which are in early-stage
clinical trials.

Other drugs are in development that
combat sarcopenia in different
ways. Muscle fibres are in a constant state
of turnover, being
simultaneously broken down and regrown,
so any compound that tips
the balance towards growth could help
build muscle mass.

One class of drug includes the compound
bimagrumab, which works by
blocking a signalling pathway targeted by
an inhibitor of muscle
growth called myostatin. Others work by
mimicking the effects of
testosterone in a safer way than existing
steroid drugs.

“There’s a lot of interest in trying to come
up with something for
sarcopenia because at the moment there’s
no treatment,” says Marks.

Indeed, it’s only within the last six months
that US researchers
have even agreed on how to define the
condition – essential before a
drug treatment can be approved. The US
National Institutes of Health
published its results in May.

“We have come a long way in how to
approach this,” says Jack
Guralnik of the University of Maryland, who
was involved in the
defining process.

In the meantime, there is already a natural
way to boost muscle:
exercise. “The mitochondrial function of
lifelong exercisers is like
that of someone half their age,” says
Moore. “One of the best
anti-ageing pills is to stay active.”

Life-saving muscle

While a six-pack is seen as the preserve of
body builders or
athletes, muscularity should be a concern
for anyone who plans on
living a long time (see main story).

As we age, our muscle fibres start to
perform less well and we lose
muscle mass – with serious consequences.
Older people with weaker
grip strength, for instance, are more likely
to die in the next few
years – even when compared with people
apparently in similar health
(BMJ, doi.org/dzn7wm).

One explanation is that as people’s
strength decreases they are more
likely to fall, and if an older person breaks a
bone and is
bed-ridden for several weeks they lose
further muscle and bone mass.
This may help to explain why 1 in 3 people
who fracture their hip in
the UK die within 12 months, according to
National Health Service
figures. “It’s a vicious circle,” says Avan
Aihie Sayer at the
University of Southampton, UK.

What’s more, muscle is the only place the
body can store amino acids
– the building blocks of proteins – so when
someone with little
muscle becomes ill they have few reserves
to call on.

Healthy muscle tissue is also a major
consumer of glucose, so lack
of muscle means the body can’t cope well
with the surge of blood
glucose after meals, which slowly nudges
people down the road to
diabetes. “People think of muscle as the
body’s mover, but it’s
really a huge metabolic organ,” says Daniel
Moore of the University
of Toronto, Canada.


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