X-Message-Number: 26772
From: 
Date: Sat, 6 Aug 2005 23:16:35 EDT
Subject: Hippocampus: May be barking up the right tree.

Hippocampus: Barking up the right tree?  

Well, more evidence of it anyway, and for very popular consumption this 
time...

From the New York Times this week.

David C. Johnson, Raleigh
Biologist & Commercial Real Estate Appraiser
______

August 2, 2005

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 Elizabeth 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.
________


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