Glutathione
(GSH) & Aging
High Glutathione levels may prevent diseases
of aging
Copyright
© 2002 1Whey2Health
Reproduction Prohibited
The
GSH antioxidant system is the body's powerhouse for diffusing
and disposing of free radicals that threaten cell, tissue and
organ damage, thus slowing the approach of aging.
John
T. Pinto of Sloan Kettering Cancer Center in New York proclaims
GSH "The master antioxidant."
Jean
Carper in her bestseller "Stop Aging Now!" highlights the same
point: "You must get your levels of GSH up if you want to keep
your youth and live longer.
High
blood levels of GSH predict good health as you age and a long
life. Low levels predict early disease and death."
These
opinions result from convincing, fascinating research and experimentation.
Age-specific decreases in GSH are seen in all tissues, including
liver, kidney, lung, heart, spleen and the brain. Laboratory studies
on the role of GSH in aging show GSH deficiency in all aging creatures,
from mosquitoes and houseflies to rats and mice.
Similar findings in humans indicate that elderly subjects bear
increased risk of disease and impairment. Blood-GSH concentrations
in younger people (20-40 years) are 20 to 40% higher than in those
aged 60-80 years.
Studies
by leading experts on aging (C.A. Lang, M. Julius and others)
suggest that elevated GSH levels give elderly individuals a
physical, psychological and sociological advantage over those
with lower levels.
Researchers
Mara Julius and Calvin Lang measured glutathione concentrations
in community-based individuals over the age of 60 years. They
found that h igher
glutathione levels corresponded to lessened effects of aging and
better general health.
Those
with 20% greater blood GSH -levels experience about one-third
the rate of arthritis, high blood -pressure, heart disease, circulatory
difficulties and other maladies.
Dr.
Lang also looked at glutathione levels in age groups: 20-40, 40-60,
60-80 and 80-100 years. The youngest group had acceptable levels
but 14% of the 40-60 year olds and 53% of the 60-80 year olds
had critically low levels.
Interestingly,
only 24% of the 80-100 year olds had low levels, perhaps explaining
how they reached such a ripe old age in the first place.
The
Italians G. Paolisso and M.R. Tagliamonte went one step further,
comparing adults under age 50 with those over 50. Both the GSH
and antioxidant function were depressed in the older group.
However,
those over 100 years old had higher GSH levels than the other
over-50 group. Again, this may explain their unusual longevity.
Several
researchers over the years have also shown that life span can
be extended by restricting diet and maintaining low body weight.
No
satisfactory explanation has emerged for this phenomenon, but
some scientists have demonstrated that glutathione levels rise
in these longer-living individuals. They
suggest that glutathione may be involved in a molecular mechanism
that contributes to longevity.
S.L.
Nuttal and his British team published a revealing study in The
Lancet, comparing GSH levels in individuals of different ages
and states of health. The healthy young had the highest levels,
ahead of the healthy elderly. The lowest levels were found in
sick, elderly patients.
The
results clearly showed that GSH levels fall as we age and as we
become ill. The more severe the illness, the more evident the
decrease.
Back
in the laboratory, scientists are trying to find out whether elevated
GSH levels can actually extend the life span. Aging-expert John
Richie Jr. thinks that glutathione deficiency may be a biochemical
cause of the aging process.
In
some of his experiments MgTC-a GSH promoting drug similar to OTC-was
fed to mosquitoes. GSH levels were found to be 50 to 100% higher,
and life span was increased by almost 40%.
In
another experiment, Diane Birt at the University of Nebraska fed
hamsters the whey-protein concentrate lactalbumin - a GSH-precursor.
These animals also lived longer.
Interestingly, control hamsters on a diet including casein and
cysteine, or methionine did not benefit. In fact high cysteine
loads proved harmful, showing how the bioactivity of these amino
acids changes when part of a larger protein, rather than free
amino acids.
Dr.
Gustavo Bounous and other researchers at McGill University demonstrated
this anti-aging effect using a natural product to elevate GSH
levels. They fed mice a specially developed whey protein isolate-later
trademarked Immunocal - and compared their GSH levels and lifespan
to mice on a standard diet.
Not
only were the tissue GSH levels found to be higher, the mice fed
un-denatured whey protein had an average life span of 27 months
(corresponding to a human age of 80 years) as compared to the
control diet average of 21 months (human equivalent of 55 years).
This is an astonishing increase of 30%.
Antioxidant
enzymes low in aging disease
NEW
YORK Jun 08 (Reuters Health) -- People with progeria --
a rare, rapid aging disease -- have low levels of the antioxidant
enzymes believed to fight aging, researchers from the University
of Iowa, Iowa City, have found.
The
results not only suggest that replacement of these enzymes may
help treat people with progeria, but they also provide insight
into the normal aging process, he said.
People
with progeria live on average to the age of 13. By the time they're
6 years old, they look like they're 60 or 70. In addition to rapid
aging, patients suffer delayed growth, a build up of fats and
cholesterol in the arteries, cardiovascular disease and other
illnesses.
Studying
progeria also enables researchers to examine the normal aging
process. "We think normal cell aging is caused by free radical
damage," said Oberley. In
their study, funded by the National Institutes of Health, Oberley
and colleagues compared skin cells of progeria patients with those
of healthy patients.
The
researchers found that in cells from progeria patients, levels
of three important antioxidant enzymes were lower than those found
in healthy cells.
Activity
levels of the enzyme catalase were 50% lower than normal, while
glutathione peroxidase activity was 70% less. In
addition, the investigators note that progeria cells respond less
well to the stress of poor nutrition compared with healthy cells.
The
results suggest two types of treatment for progeria, he said.
For short-term treatment, existing drugs that mimic the missing
enzymes can be studied.
A
long-term solution is to use genetic engineering to deliver genes
coding for the enzymes into the cells of progeria patients. This
way, the genes will be able to produce the missing enzymes in
the body.
Research
in this area is at an early stage, but may be applicable to many
diseases including cancer, heart disease, stroke or diabetes,
said Oberley.
SOURCE: Biochemical and Biophysical Research
Communications 1999;257:163-167.
Articles and Research Publications on Glutathione and Aging
The
Life Extension Protein that Fights Disease And Extends Lifespan
(LE Magazine January 1996) - By Will Brink
The
influence of dietary whey protein on tissue glutathione and the
diseases of aging
Bounous G, Gervais F, Amer V, Batist G, Gold P Montreal General
Hospital Research Institute, Quebec. "Hence a whey protein
diet appears to enhance the liver and heart glutathione concentration
in aging mice and to increase longevity over a 6.3 month observation
period. "
Relationships
between the cellular glutathione level and in vitro life span
of human diploid fibroblasts
Honda S, Matsuo M [Exp Gerontol 1988;23(2):81-6.] In order
to examine the role of cellular glutathione (GSH) in the in vitro
aging of human diploid fibroblasts, we studied the effects of
manipulated cellular GSH levels on their in vitro life span. An
increase in cellular GSH level was produced by the addition of
N-acetylcysteine (NAC), a carrier of cysteine across cell membranes,
into the culture medium, while a decrease in GSH level was produced
by the addition of L-buthionine-(R,S)-sulfoximine (BSO), a specific
inhibitor of GSH synthetase. When the cells were serially subcultivated
in a medium containing NAC or BSO, their life spans were markedly
extended or shortened, respectively, in comparison to the life
span of cells grown in a control medium. These results suggest
that the cellular GSH level is a determinant of the in vitro
life span of human diploid cells.
Glutathione
in human plasma: Decline in association with aging, age- related
macular degeneration, and diabetes
Samiec
PS, Drews-Botsch C, and others. [Free Radic Biol Med 1998
Mar 15;24(5):699-704.]
Glutathione
biosynthesis influences replicative longevity in Saccharomyces
cerevisiae
Zandycke SM, Smart KA. [ScientificWorldJournal. 2001
Jan 1;1(1 Suppl 3):133.]
The yeast Saccharomyces cerevisiae possesses a finite lifespan;
the metric of which is the number of times the cell divides and
not its chronological age (1). The free radical theory of ageing
postulates that reactive oxygen species are causal factors in
ageing (2). These species are capable of damaging DNA, protein
and lipids within the cell. For defence against these
prooxidants, cells contain antioxidant molecule such as glutathione
(GSH).
High
blood glutathione levels accompany excellent physical and mental
health in women ages 60 to 103 years
Lang CA, Mills BJ, Lang HL, Liu MC, Usui WM, Richie J Jr,
Mastropaolo W, Murrell SA. [J Lab Clin Med. 2002 Dec;140(6):413-7.]
Earlier we found a high percentage of subnormal total glutathione
(G(T)) levels in blood from elderly subjects and patients with
chronic diseases. These findings suggested a hypothesis that high
levels of G(T) in the blood occur in old persons who are in excellent
physical and mental health. To this end, we recruited 87 white
women who ranged in age from 60 to 103 years and reported that
they felt healthy. Their health was verified with physical examinations,
clinical chemistry profiles, psychosocial assessments, and blood
G(T) determinations. This evaluation was performed in three waves
over a 5-year period. The values were compared with those from
representative individuals in this region and with normal national
data. The results verified that these healthy subjects were in
top physical and mental health. We also found that subjects of
all ages had very high blood G(T) levels in waves I and II but
only normal levels in wave III. These findings confirm that high
blood G(T) concentrations and excellent physical and mental health
are characteristics of long-lived women.
Increased
oxidative stress with aging reduces chondrocyte survival: correlation
with intracellular glutathione levels
Carlo MD Jr, Loeser RF. [Arthritis Rheum. 2003 Dec; 48(12):
3419-30.] Cells depleted of intracellular glutathione were more
susceptible to cell death induced by SIN-1. These results provide
evidence that increased oxidative stress with aging makes chondrocytes
more susceptible to oxidant-mediated cell death through the dysregulation
of the glutathione antioxidant system. This may represent an important
contributing factor to the development of osteoarthritis in older
adults.
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