76 BBC SCIENCE FOCUS MAGAZINE COLLECTION
SLEEPA mitochondrion, a cell’s
‘power pack’, has a highly
folded inner membrane
that’s packed with
substances involved in the
creation of ATP, which the
body uses for energyAt a cel lu la r level, scient ist s a re i nc rea si ng ly
looking at the role of mitochondria – the power
packs in every human cell – in determining
how tired we feel. Mitochondria are miniature
organs (organelles) that convert oxygen, sugar,
fats and protein into a form of chemical energy,
called ATP, which the body uses to fuel the
brain and muscles. Diseases affecting the
mitochondria cause fatigue, so recent reviews of
research suggest that fatigue is closely associated
with mitochondria not working properly
because the body is not producing particular
enzymes, for example.
Studies into CFS/ME by fatigue expert
Dr Robert Naviaux have shown that the condition
is characterised by changes in mitochondria
function. Dr Naviaux believes that these changes
may be triggered by stressors such as infection,
or physical and psychological trauma.
Dr Naviaux cites new literature indicating that
stress can prompt metabolic changes, which
make organisms go into hibernation-like states
such as torpor and aestivation. “Both of these
is an energy conservation state that permits
survival under conditions of environmental
stress at the expense of a decrease in the ability
to a l locate ener g y for da ily work or ac t iv it y,” he
says. “Mitochondria are central control points
for each of these processes.”
This initial research about the metabolic
origins of fatigue may link with other studies
suggesting that sometimes tiredness has
underlying but undiscovered physical origins.
For example, recent studies have indicated that
severe fat ig ue is a ssociated w it h ra ised levels of
leptin, a hormone produced in fat tissue, which
signals to the brain that the body has adequate
energy stores. This raises the prospect that too
much leptin – possibly from too much body
fat – means we naturally feel less energetic:
if we don’t need food we don’t need to go out
and do something about it. This links with
anecdotal evidence that intermittent fasting
and reducing body fat can improve people’s
energy levels.
It also links with research indicating that
people with CFS/ME can have high levels of
leptin and similar inflammation-producing
substances called cytokines. Cytokines, which
are also produced in fat, are released during5 Until now, little has been known about the
biolog ica l processes t hat resu lt i n what we ca l l
tiredness or fatigue. Only in recent decades,
with growing concern about the prevalence
of conditions such as CFS/ME, has research
money been invested into the causes of long-
term fatigue. As a result it’s becoming clear
that, although there is a wide spectrum of
types of tiredness, they are all linked and their
causes interact.
Prof Julia Newton, director of the Newcastle
Centre for Fatigue Research at Newcastle
University, explains the causes of tiredness
via a classic bell-shaped curve graph. “At the
thin end of the curve, there are people who just
need to get some sleep and get their lifestyle
in order. At the other thin end of the curve
there are clearly people who have diagnosed or
undiagnosed illnesses that are causing fatigue.
And then, there’s everyone else in the wide,
middle part of curve.”
The wide middle is the complex bit, covering
tiredness caused by combinations of many
environmental, lifestyle and health factors.
And recent research is beginning to reveal
how genetics, cell function, inflammation and
the brain’s response to light may all have an
underlying role in this tiredness ‘mainstream’.Some of us may simply
have been born with a
physical and psychological
susceptibility to tiredness