Dietary Supplements Make Old Rats Youthful, May Help Rejuvenate Aging Hu

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Dietary Supplements Make Old Rats Youthful, May Help Rejuvenate

Aging Humans

JoAnn Guest

Jan 09, 2007 10:10 PST

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Dietary Supplements Make Old Rats Youthful, May Help Rejuvenate

Aging Humans, According To UC Berkeley Study

 

http://www.willner.com/article.aspx?artid=8

 

Two dietary supplements straight off the health food store shelf put

the spark back into aging rats, and might do the same for aging baby

boomers, according to a study at the University of California,

Berkeley, and Children's Hospital Oakland Research Institute.

 

A team of researchers led by Bruce N. Ames, professor of molecular

and cell biology at UC Berkeley, fed older rats two chemicals

normally found in the body's cells and available as dietary

supplements: acetyl-L-carnitine and an antioxidant, alpha-lipoic

acid.

 

In three articles in the February 19 issue of Proceedings of the

National Academy of Sciences, Ames and his colleagues report the

surprising results. Not only did the older rats do better on memory

tests, they had more pep, and the energy-producing organelles in

their cells worked better.

 

" With the two supplements together, these old rats got up and did

the Macarena, " said Ames, also a researcher at Children's Hospital

Oakland Research Institute (CHORI). " The brain looks better, they

are full of energy - everything we looked at looks more like a young

animal. "

 

" The animals seem to have much more vigor and are much more active

than animals not on this diet, signaling massive improvement to

these animals' health and well-being, " said former UC Berkeley post-

doctoral fellow Tory M. Hagen, now an assistant professor at the

Linus Pauling

Institute at Oregon State University, Corvallis. " And we also see a

reversal in loss of memory. That is a dual-track improvement that is

significant and unique. This is really starting to explode and move

out of the realm of basic research into people. "

 

Based on the group's earlier studies, the University of California

patented use of the combination of the two supplements to rejuvenate

cells. Ames, through the Bruce and Giovanna Ames Foundation, and

Hagen founded a company in 1999 called Juvenon to license the patent

from the

university. Juvenon currently is engaged in human clinical trials of

the

combination.

 

One of the three PNAS articles probes the reasons behind this

rejuvenation, concluding that the two chemicals " tune up " the

energy-producing organelles that power all cells, the mitochondria.

Both

chemicals are normally used in mitochondria.

 

Ames calls mitochondria the " weak link in aging. " Evidence has been

piling up, he said, that deterioration of mitochondria is an

important

cause of aging. A significant cause of this deterioration, he

believes,

is the accumulation of destructive free radicals - byproducts of

normal

metabolism - that disable enzymes and other chemicals.

 

The combination therapy targets mitochondria to get rid of

destructive

radicals and to boost the activity of a damaged enzyme, carnitine

acetyltransferase, that plays a key role in burning fuel in

mitochondria. The researchers hoped that the anti-oxidant alpha-

lipoic

acid would do the former, and that flooding the cell with

acetyl-L-carnitine, one of two proteins that the enzyme acts on,

would

achieve the latter.

 

Experiments showed that this regimen worked. Associate researcher

Jiankang Liu of CHORI, UC Berkeley postdoctoral fellow David W.

Killilea

and Ames demonstrated that the enzyme carnitine acetyltransferase is

less active in old rats than in young rats, and that it binds less

tightly to acetyl-L-carnitine in older rats.

 

Supplementation with acetyl-L-carnitine or a combination of

acetyl-L-carnitine and alpha-lipoic acid restored the enzyme's

activity

nearly to that found in young rats and substantially restored

binding to

acetyl-L-carnitine.

 

" The acetyl-L-carnitine is protecting the protein and the higher

levels

are enabling the protein to work, while alpha-lipoic acid knocks

down

oxygen radicals, " Ames said. " Each chemical solves a different

problem -

the two together are better than either one alone. "

 

Ames and Hagen have long had an interest in mitochondria as they

relate

to aging, and they were intrigued by a 1999 Italian study that

showed

acetyl-L-carnitine, when fed to old rats, improved mitochondrial

activity.

 

The two thought this might be a way to reverse the effects of aging

on

mitochondria, and in various trials found it to work to some degree.

Free radicals were still damaging the cell, however, so they decided

to

pair it with one of the few antioxidants that gets into

mitochondria,

alpha-lipoic acid. Lipoic acid is produced by mitochondria and

boosts

levels of other antioxidants.

 

In the second of the PNAS studies, Hagen, Ames and colleagues

compared

2- to 4-month-old rats to 24- to 28-month-old rats, all fed

acetyl-L-carnitine in their water and alpha-lipoic acid in their

chow.

 

After as much as a month on the supplements, the old and lethargic

rats

became more peppy, Ames said.

 

" We significantly reversed the decline in overall activity typical

of

aged rats to what you see in a middle-aged to young adult rat 7 to

10

months of age, " Hagen said. " This is equivalent to making a 75- to

80-year-old person act middle-aged. We've only shown short-term

effects,

but the results give us the rationale for looking at these things

long

term. "

 

They found also that the combination of lipoic acid and acetyl-

carnitine

improved mitochondrial activity and thus cellular metabolism, and

increased levels of various chemicals known to decline with age,

including ascorbic acid, an antioxidant.

 

In a third study, Liu, Hagen, Ames and colleagues fed old rats a

similar

diet of the two supplements and looked at memory function as

measured by

the Morris water maze test and a peak procedure for assessing

temporal

or time-based memory developed by Seth Roberts, professor of

psychology

at UC Berkeley. They found that supplementation improved both

spatial

and temporal memory, and reduced the amount of oxidative damage to

RNA

in the brain's hippocampus, an area important in memory. In electron

microscope pictures of cells from the hippocampus, mitochondria

showed

less structural decay in old rats that had a supplemented diet.

 

" We did two different tests for cognitive activity in rats, and in

both

it made a big difference to feed them this mixture, " Ames

said. " Memory

degenerates with age, and this makes them better. "

 

The analysis of nucleic acid damage in the brain was performed with

post-doctoral researcher Elizabeth Head and Carl W. Cotman,

professor of

neurobiology and behavior, at the Institute for Brain Aging and

Dementia

at UC Irvine. UC Berkeley psychology graduate student Afshin M.

Gharib

worked with Liu to conduct the peak performance tests.

 

" In aging, you're oxidizing the proteins in mitochondria and they

lose

activity, " Ames explained. " If some of that lost activity is due to

binding for substrate or coenzyme - like binding of acetyl-L-

carnitine

by carnitine acetyltransferase - and you can raise the level of

those,

then you can reverse some of the loss.

 

" We showed, in fact, that that is what's happening with

acetyl-L-carnitine. Aldehydes from lipid oxidation are glomming onto

that protein, and that is what appears to cause the reduction in

binding

activity. But if you raise the level of acetyl-L-carnitine, now it

works. "

Hagen added, " With aging, we see so many different things that are

occurring to mitochondria that then lead to consequences in the

cell. If

you tune up mitochondria you may have a means of at least delaying

the

onset of a number of age-related problems that we encounter, or we

can

in some ways, hopefully, reverse what has already taken place. "

 

The work was supported by grants from the Ellison Foundation, the

National Institute on Aging of the National Institutes of Health,

the

Wheeler Fund of the Dean of Biology at UC Berkeley, the Bruce and

Giovanna Ames Foundation and the National Institute of Environmental

Health Sciences Center at UC Berkeley. www.Berkeley.edu

 

 

 

JoAnn Guest

mrsjo-

www.geocities.com/mrsjoguest/Diets