Twenty
years ago, if you'd mentioned free radicals
to the average person, they would probably have
thought you were talking about campus political
dissidents. Today, almost everyone has at least
some familiarity free radicals and their harmful
effects - which is why health-conscious people
always have their ears perked up for news on the
latest antioxidant to hit the market.
But
even after a generation of attention on the role
of free radicals in health and disease, many health-conscious
people still don't know that, while some free
radicals come into the body from the environment
(such as from smog, rancid fats, and ultraviolet
radiation),most free radicals are actually produced
by the body itself. Some free radicals are used
by the body's immune cells to kill off invaders.
Others are produced by the enzymes that help your
body break down toxins. Even the ability of your
blood vessels to relax and allow blood to flow
is dependent on production of a kind of free radical
(nitric oxide).
At
Ground Zero
And in fact, the single biggest source
of free radicals in your body are its mitochondria
57
Elsewhere in this article, we've referred to mitochondria
as the cell's "power plants." But "nuclear
power plants" might be a more precise image.
Because as part of the process of energy production,
both nuclear plants and mitochondria also produce
deadly, high-energy waste. In the case of mitochondria,
that waste is a free radical called superoxide.
This
means that the body's cellular power plants are
the site of an ongoing "reactor leak,"
exposing them to the biggest load of free radical
marauders in the body. And unfortunately, while
your body produces antioxidant enzymes which can
partially protect the rest of the cell from free
radical damage, these enzymes are much less able
to protect the mitochondria.
A
striking example of the greater vulnerability
of mitochondria to free radical damage is the
extent of the damage suffered by their DNA, which
is separate from the DNA of the rest of the cell.
While health-conscious people are rightly concerned
about free radical damage to the DNA blueprints
of the cell as a whole, the number of hits to
the main genetic code pales next to the level
of damage suffered by mitochondrial DNA. When
you look at the cells of key organs like the brain
and heart - the long-lived cell types that normally
must last a lifetime - you see that mitochondrial
DNA suffers seven to eleven times more damage
from free radicals than does the DNA for the rest
of the cell.
58
,
59,
60
The
picture doesn't get any prettier when you look
at the working parts of the mitochondria
- a system we've only recently begun to truly
understand. Remarkably, as scientists have pieced
together the mechanism wherebymitochondria generate
energy, it's become clear that mitochondria
create power using almost identical principles
to the ones used by hydroelectric dams - right
down to the turbines (see Figure 7)!
,
61,
62
In simple terms, mitochondria take energy from
food, and use it to build up a "reservoir"
of hydrogen ions (H+) behind a "dam"
(the mitochondrial inner membrane). The
buildup of ions behind the "dam" creates
a force drawing them to the "downhill"
side of the mitochondrial inner membrane, just
as water behind a dam is drawn downward by gravity.
The "dam" leaves only one route for
the ions to flow: through a quite literal
turbine called "Complex V" (or
the "F0/F1 ATP synthase"). The flow
of ions through Complex V literally causes its
turbine to spin, and this motion drives the joining
of a carrier molecule (adenosine diphosphate,
ADP) with a high-energy phosphate bond, to create
the "universal energy molecule"
of life: ATP (adenosine triphosphate).
So
guess what happens when the moving parts of your
turbine start to wear out, and you start getting
cracks in your hydro dam?
You
get the picture. With age, the mitochondrial
"dam" literally becomes leakier,
allowing hydrogen ions to escape across the mitochondrial
inner membrane without powering the Complex V
turbine
63
A key part of this loss of membrane function is
free radical damage in the proteins of the mitochondria,
which slowly creeps up with age
64
Just as a leaking dam reduces the water levels
behind it (and thus, the potential energy which
is available to drive the dam's electrical turbines),
so a leaky mitochondrial inner membrane reduces
the amount of force available to push ions through
the ATP turbines of Complex V.
As
a result, old organisms' mitochondria have
less membrane energy potential than do young ones,
and produce less ATP
63 (a fact which can be measured
using mitochondrial oxygen use). In addition to
seriously compromising your cellular energy supply
(and especially the ability of the cell to increase
energy output to meet unusually high energy demands
under stressful conditions), this mitochondrial
energy inefficiency has another cost. Remember,
the process of maintaining the ion "reservoir"
creates waste, in the form of superoxide free
radicals. When there are leaks in the "dam,"
it takes more and more "pumping" of
ions to create a given amount of energy, because
fewer of the ions that are moved into the "reservoir"
will ultimately generate energy by passing through
the Complex V turbines.
The
consequence: old animals' mitochondria "burn"
their fuel less and less cleanly, churning out
more and more free radical waste per unit of useable
energy produced.
63,
65,
66
, It's a vicious circle: as mitochondria decay,
the cell's power situation looks more and more
like a California brown-out, even as the cell's
need for energy is increased by the greater and
greater load of choking free radicals … which
come precisely from its increasingly polluting
"power plants."
Less
energy. More free radicals. The flames of life
grow smoky and dim. Without energy, the cell can't
perform its essential functions in the body. Proteins
aren't made; chemicals aren't detoxified; hearts
don't pump; wounds don't heal. Youth fades. Organisms
age … and die.
How
can you get that youthful energy production back?
