Scientists stop the aging process

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Posted in Longevity and Age Management, Aging, Longevity on Fri August

15, 2008

Scientists have stopped the aging process in an entire organ for the

first time, a study released today says.

Published in today's online edition of Nature Medicine, researchers at

the Albert Einstein College of Medicine at Yeshiva University in New

York City also say the older organs function as well as they did when

the host animal was younger.

The researchers, led by Associate Professor Ana Cuervo, blocked

the aging process in mice livers by stopping the build-up of harmful

proteins inside the organ's cells.

As people age their cells become less efficient at getting rid of

damaged protein resulting in a build-up of toxic material that is

especially pronounced in Alzheimer's, Parkinson's and other

neurodegenerative disorders.

The researchers say the findings suggest that therapies for boosting

protein clearance might help stave off some of the declines in

function that accompanies old age.

In experiments, livers in genetically modified mice 22 to 26 months

old, the equivalent of octogenarians in human years, cleaned blood as

efficiently as those in animals a quarter their age.

By contrast, the livers of normal mice in a control group began to fail.

The benefits of restoring the cleaning mechanisms found inside all

cells could extend far beyond a single organ, says Cuervo.

" Our findings are particularly relevant for neurodegenerative

disorders such as Parkinson's and Alzheimer's, " she says.

'Misbehaving proteins'

" Many of these diseases are due to 'misbehaving' or damaged proteins

that accumulate in neurons. By preventing this decline in protein

clearance, we may be able to keep these people free of symptoms for a

longer time. "

If the body's ability to dispose of cell debris within the cell were

enhanced across a wider range of tissues, she says, it could extend

life as well.

In healthy organisms, a surveillance system inside cells called

chaperone-mediated autophagy (CMA) locates, digests and destroys

damaged proteins.

Specialized molecules, the " chaperones " , ferry the harmful material to

membrane-bound sacs of enzymes within the cells known as lysosomes.

Once the cargo has been " docked " , a receptor molecule transfers the

protein into the sac, where it is rapidly digested.

With age, these receptors stop working as well, resulting in a

dangerous build-up of faulty proteins that has been linked, in the

liver, to insulin resistance as well as the inability to metabolize

sugar, fats or alcohol.

The same breakdown of the cell's cleaning machinery can also impair

the liver's ability to remove the toxic build-up of drugs at a stage

in life when medication is often part of daily diet.

In genetically modified mice, Cuervo compensated for the loss of the

receptors in the animals by adding extra copies.

" That was enough to maintain a clean liver and to prove that if you

keep your cells clean they work better, " she says.

Settles debate

The study goes a long way towards settling a sharp debate in the field

of aging research.

Leading Australian aging researcher le Couteur, Professor of

Geriatric Medicine at the University of Sydney, says the paper is a

major breakthrough.

" She has single-handedly shown that lysosome function is a crucial

part of the aging process, " he says.

Cuervo has also shown, he says, the critical role the lysosomal

receptor molecules play in keeping the liver clean of damaged proteins.

While her paper does not show increased survival rates among the mice,

le Couteur, who has advised her recently on the research, says Cuervo

does have data on improved survival rates which she intends to publish.

He also says she is now working with pharmaceutical companies to

identify drugs that will turn the receptors on, or make them more active.

Cuervo believes maintaining efficient protein clearance may improve

longevity and function in all the body's tissues.

It is also possible that the same kind of " cellular clearance " can be

achieved through diet, she says.

Research over the past decade has shown that restricted calorie intake

in animals, including mammals, significantly enhances longevity.

" My ideal intervention in the future would be a better diet rather

than a pill, " she says.

RESOURCE/SOURCE:

http://www.abc.net.au/science/articles/2008/08/11/2331197.htm?site=science

on Monday, AUgust 11, 2008