Measuring the age of our cells

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Exercise may not help stave off the inevitable but in many ways we

are younger than we think.

Mike

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Your Body Is Younger Than You Think

By NICHOLAS WADE

Whatever your age, your body is many years younger. In fact, even if

you're middle aged, most of you may be just 10 years old or less.

This heartening truth, which arises from the fact that most of the

body's tissues are under constant renewal, has been underlined by a

novel method of estimating the age of human cells. Its inventor,

Jonas Frisen, believes the average age of all the cells in an

adult's body may turn out to be as young as 7 to 10 years.

But Dr. Frisen, a stem cell biologist at the Karolinska Institute in

Stockholm, has also discovered a fact that explains why people

behave their birth age, not the physical age of their cells: a few

of the body's cell types endure from birth to death without renewal,

and this special minority includes some or all of the cells of the

cerebral cortex.

It was a dispute over whether the cortex ever makes any new cells

that got Dr. Frisen looking for a new way of figuring out how old

human cells really are. Existing techniques depend on tagging DNA

with chemicals but are far from perfect. Wondering if some natural

tag might already be in place, Dr. Frisen recalled that the nuclear

weapons tested above ground until 1963 had injected a pulse of

radioactive carbon 14 into the atmosphere.

Breathed in by plants worldwide and eaten by animals and people, the

carbon 14 gets incorporated into the DNA of cells each time the cell

divides and the DNA is duplicated.

Most molecules in a cell are constantly being replaced but the DNA

is not. All the carbon 14 in a cell's DNA is acquired on the cell's

birth date, the day its parent cell divided. Hence the extent of

carbon 14 enrichment could be used to figure out the cell's age, Dr.

Frisen surmised. In practice, the method has to be performed on

tissues, not individual cells, because not enough carbon 14 gets

into any single cell to signal its age. Dr. Frisen then worked out a

scale for converting carbon 14 enrichment into calendar dates by

measuring the carbon 14 incorporated into individual tree rings in

Swedish pine trees.

Having validated the method with various tests, he and his

colleagues have reported in the July 15 issue of Cell the results of

their first tests with a few body tissues. Cells from the muscles of

the ribs, taken from people in their late 30's, have an average age

of 15.1 years, they say.

The epithelial cells that line the surface of the gut have a rough

life and are known by other methods to last only five days. Ignoring

these surface cells, the average age of those in the main body of

the gut is 15.9 years, Dr. Frisen found.

The Karolinska team then turned to the brain, the renewal of whose

cells has been a matter of much contention. Prevailing belief, by

and large, is that the brain does not generate new neurons after its

structure is complete, except in two specific regions, the olfactory

bulb that mediates the sense of smell, and the hippocampus, where

initial memories of faces and places are laid down.

This consensus view was challenged a few years ago by

Gould of Princeton, who reported finding new neurons in the cerebral

cortex, along with the elegant idea that each day's memories might

be recorded in the neurons generated that day.

Dr. Frisen's method will enable all regions of the brain to be dated

to see if any new neurons are generated. So far he has tested only

cells from the visual cortex. He finds these are exactly the same

age as the individual, showing that new neurons are not generated

after birth in this region of the cerebral cortex, or at least not

in significant numbers. Cells of the cerebellum are slightly younger

than those of the cortex, which fits with the idea that the

cerebellum continues developing after birth.

Another contentious issue is whether the heart generates new muscle

cells after birth. The conventional view that it does not has

recently been challenged by Dr. Piero Anversa of the New York

Medical College in Valhalla. Dr. Frisen has found the heart as a

whole is generating new cells, but he has not yet measured the

turnover rate of the heart's muscle cells.

Although people may think of their body as a fairly permanent

structure, most of it is in a state of constant flux as old cells

are discarded and new ones generated in their place. Each kind of

tissue has its own turnover time, depending in part on the workload

endured by its cells. The cells lining the stomach, as mentioned,

last only five days. The red blood cells, bruised and battered after

traveling nearly 1,000 miles through the maze of the body's

circulatory system, last only 120 days or so on average before being

dispatched to their graveyard in the spleen.

The epidermis, or surface layer of the skin, is recycled every two

weeks or so. The reason for the quick replacement is that " this is

the body's saran wrap, and it can be easily damaged by scratching,

solvents, wear and tear, " said Elaine Fuchs, an expert on the skin's

stem cells at the Rockefeller University.

As for the liver, the detoxifier of all the natural plant poisons

and drugs that pass a person's lips, its life on the chemical-

warfare front is quite short. An adult human liver probably has a

turnover time of 300 to 500 days, said Markus Grompe, an expert on

the liver's stem cells at the Oregon Health & Science University.

Other tissues have lifetimes measured in years, not days, but are

still far from permanent. Even the bones endure nonstop makeover.

The entire human skeleton is thought to be replaced every 10 years

or so in adults, as twin construction crews of bone-dissolving and

bone-rebuilding cells combine to remodel it.

About the only pieces of the body that last a lifetime, on present

evidence, seem to be the neurons of the cerebral cortex, the inner

lens cells of the eye and perhaps the muscle cells of the heart. The

inner lens cells form in the embryo and then lapse into such

inertness for the rest of their owner's lifetime that they dispense

altogether with their nucleus and other cellular organelles.

But if the body remains so perpetually youthful and vigorous, and so

eminently capable of renewing its tissues, why doesn't the

regeneration continue forever?

Some experts believe the root cause is that the DNA accumulates

mutations and its information is gradually degraded. Others blame

the DNA of the mitochondria, which lack the repair mechanisms

available for the chromosomes. A third theory is that the stem cells

that are the source of new cells in each tissue eventually grow

feeble with age.

" The notion that stem cells themselves age and become less capable

of generating progeny is gaining increasing support, " Dr. Frisen

said. He hopes to see if the rate of a tissue's regeneration slows

as a person ages, which might point to the stem cells as being what

one unwetted heel was to Achilles, the single impediment to

immortality.