I could sure have used something like this after my instant decreptitude of my stroke.
http://www.nature.com/news/2010/101128/full/news.2010.635.html
Premature ageing can be reversed by reactivating an enzyme that protects the tips of chromosomes, a study in mice suggests.
Mice engineered to lack the enzyme, called telomerase, become
prematurely decrepit. But they bounced back to health when the enzyme
was replaced. The finding, published online today in
Nature1, hints that some disorders characterized by early ageing could be treated by boosting telomerase activity.
It also offers the possibility that normal human ageing could be
slowed by reawakening the enzyme in cells where it has stopped working,
says Ronald DePinho, a cancer geneticist at the Dana-Farber Cancer
Institute and Harvard Medical School in Boston, Massachusetts, who led
the new study. "This has implications for thinking about telomerase as a
serious anti-ageing intervention."
Other scientists, however, point out that mice lacking telomerase
are a poor stand-in for the normal ageing process. Moreover, ramping up
telomerase in humans could potentially encourage the growth of tumours.
Eternal youth
After its discovery in the 1980s, telomerase gained a reputation as a
fountain of youth. Chromosomes have caps of repetitive DNA called
telomeres at their ends. Every time cells divide, their telomeres
shorten, which eventually prompts them to stop dividing and die.
Telomerase prevents this decline in some kinds of cells, including stem
cells, by lengthening telomeres, and the hope was that activating the
enzyme could slow cellular ageing.
Two decades on, researchers are realizing that telomerase's role in
ageing is far more nuanced than first thought. Some studies have
uncovered an association between short telomeres and early death,
whereas others have failed to back up this link. People with rare
diseases characterized by shortened telomeres or telomerase mutations
seem to age prematurely, although some tissues are more affected than
others.
“They are not studying normal ageing, but ageing in mice made grossly abnormal.”
When
mice are engineered to lack telomerase completely, their telomeres
progressively shorten over several generations. These animals age much
faster than normal mice — they are barely fertile and suffer from
age-related conditions such as osteoporosis, diabetes and
neurodegeneration. They also die young. "If you look at all those data
together, you walk away with the idea that the loss of telomerase could
be a very important instigator of the ageing process," says DePinho.
To find out if these dramatic effects are reversible, DePinho's team
engineered mice such that the inactivated telomerase could be switched
back on by feeding the mice a chemical called 4-OHT. The researchers
allowed the mice to grow to adulthood without the enzyme, then
reactivated it for a month. They assessed the health of the mice another
month later.
"What really caught us by surprise was the dramatic reversal of the
effects we saw in these animals," says DePinho. He describes the outcome
as "a near 'Ponce de Leon' effect" — a reference to the Spanish
explorer Juan Ponce de Leon, who went in search of the mythical Fountain
of Youth. Shrivelled testes grew back to normal and the animals
regained their fertility. Other organs, such as the spleen, liver and
intestines, recuperated from their degenerated state.
The one-month pulse of telomerase also reversed effects of ageing in
the brain. Mice with restored telomerase activity had noticeably larger
brains than animals still lacking the enzyme, and neural progenitor
cells, which produce new neurons and supporting brain cells, started
working again.
"It gives us a sense that there's a point of return for
age-associated disorders," says DePinho. Drugs that ramp up telomerase
activity are worth pursuing as a potential treatment for rare disorders
characterized by premature ageing, he says, and perhaps even for more
common age-related conditions.
Cancer link
The downside is that telomerase is often mutated in human cancers, and
seems to help existing tumours grow faster. But DePinho argues that
telomerase should prevent healthy cells from becoming cancerous in the
first place by preventing DNA damage.
David Sinclair, a molecular biologist at Harvard Medical School in
Boston, agrees there is evidence that activating telomerase might
prevent tumours. If the treatment can be made safe, he adds, "it could
lead to breakthroughs in restoring organ function in the elderly and
treating a variety of diseases of aging."
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Other researchers are less confident that telomerase can be safely
harnessed. "Telomere rejuvenation is potentially very dangerous unless
you make sure that it does not stimulate cancer," says David Harrison,
who researches ageing at the Jackson Laboratory in Bar Harbor, Maine.
Harrison also questions whether mice lacking telomerase are a good
model for human ageing. "They are not studying normal ageing, but ageing
in mice made grossly abnormal," he says. Tom Kirkwood, who directs the
Institute for Ageing and Health at Newcastle University, UK, agrees,
pointing out that telomere erosion "is surely not the only, or even
dominant, cause" of ageing in humans.
DePinho says he recognizes that there is more to ageing than
shortened telomeres, particularly late in life, but argues that
telomerase therapy could one day be combined with other therapies that
target the biochemical pathways of ageing. "This may be one of several
things you need to do in order to extend lifespan and extend healthy
living," he says.
