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The Care and Feeding of Our Genes: Managing the Good, the Bad, Even the Ugly |
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by Parris M. Kidd, Ph.D.
- My parents both lived into their nineties, so I should have a long life.
- My father died of a heart attack at 49, and I probably have bad heart genes.
- Both my parents died of cancer. Im terrified Ill get cancer too.
How much do we really owe
to our genes? What can we
do with the genes we have,
the genetic hand we were
dealt, to achieve a long and
healthy life?
Each of our cells carries a set of 46 chromosomes,
each chromosome many genes. The total panoply of genes is called the
genome. Each gene is a DNA blueprint that
specifies the structure of one protein. The
genes are the blueprints, the proteins are the
facilitators. Our proteins feed back to our
genes as our cells respond to changes in their
internal micro-environments with changes
in gene activity. Different gene sets are constantly
being turned on or turned off, in a
yin-yang dynamic between gene and environment.
The Human Genome Project came up
with a minimum 30,000 as the number of
different genes humans carry (with a lot of
DNA leftoverlike the parts that remained
after you assembled your kids bike).
Probably all 30,000 genes arent simultaneously
active in one cell. Instead, sets of genes
become selectively activated to make the different
cell types.
Gene-environment interactions manage
our entire biochemistry and ultimately our
total health and resistance against disease.
For the good genes, a supportive good environment
means routine high performance.
Bad genes often sputter even in a good
environment; the ongoing quality of their
micro-environment determines when they
breakthrough to cause disease. Real-life environmental
factors such as lifestyle, diet,
stress, toxic load and nutrient status all
regulate gene expression.
Good genes and bad genes may begin
with grandparents. For our mothers, the
quality of their mothers uterine environmentor at an earlier stage, the quality of
their egg-sperm unionsinfluenced their
lifelong health for good or bad. In turn, our lifelong health was influenced by our eggsperm
union and the uterine environments
our mothers provided. The fathers side may
also prove to have similar trans-generational
influence. This doesnt mean that if your
grandparents or your parents didnt take care
of themselves, you are necessarily doomed to a short and sickly life. By providing a good,
supportive environment for your genes you
positively influence your health and
longevity.
Some kids do get dealt a bad genetic
hand. Autistic kids almost all have problems
to process toxins and clear them from the
body. It may well be that these same children
born into a world free of mercury and other
environmental pollutants would not become
autistic; unfortunately the modern American
environment doesnt afford that possibility. A
similar scenario applies to ADHD (attention
deficit-hyperactivity disorder), less genetically
conditioned than autism but also linked
to maternal or early childhood exposure to
toxins.
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| The Human Genome Project came up with a minimum 30,000 as the number of different genes humans carry (with a lot of DNA leftoverlike the parts that remained after you assembled
your kids bike). Probably all 30,000 genes arent simultaneously active in one cell. Instead,
sets of genes become selectively activated to make the different cell types. |
In adult life theres Parkinsons disease, for
which a single brief toxic exposure may initiate
inflammation that years later manifests
as disease. A few people with heavy genetic disposition to Parkinsons develop it in their
40s or early 50s; those with a milder genic
load manifest in their 60s or even 70s;
mineworkers can get it through exposure to
manganese, without having any known susceptibility
genes.
Some people have an inherited predisposition
to major depression, bipolar disorder
(manic-depressive illness) or schizophrenia.
A spectrum of different genes may work
together in differing combinations to determine
which of these conditions (more often,
a mixture) will develop. The susceptible individual
can be transformed from health to mental illness by one bad life event. In bipolar
disorder, the stress of a high school graduation
or the trauma of childhood sexual abuse sometimes
will suffice.
The fragile DNA strands that are our genes
are highly susceptible to damage. The great
Berkeley researcher Dr. Bruce Ames has argued
that nutrient deficiencies can mimic radiation
and toxic chemicals to cause DNA damage that
possibly leads to cancer. He lists deficiencies in
folic acid, vitamin B12, vitamin B6, niacin,
vitamin C, vitamin E, iron, or zinc in this category.
Up to 20 percent of the U.S. population
has one or more of these deficiencies. Professor
Ames suggested this may explain why the
quarter of the population that eats the fewest
fruits and vegetables has about double the
cancer rate compared to the quarter with the
highest intake.
The Ames research underscores that even
good genes require favorable biochemical environments.
The person whose two parents lived
into their 90s isn't guaranteed that for himself.
Our DNA being so fragile, our chromosomes so
vulnerable to toxins, our daily environment so
contaminated, we have no guarantees of long
life. We have to protect our genes.
The flip side of this reality is that the fellow
whose dad died of a heart attack at 49 could
live to 100 or more. He could exercise regularly,
watch his blood pressure, keep his weight
down, avoid emotional stress, eat healthy
foods and get regular cardiac checkups. He
would monitor not just his blood lipid levels
but other measurable circulatory risk factors
such as CRP (C-reactive protein) and homocysteine.
Vitamin C and other antioxidants as well
as omega-3 fatty acids would further improve
his chances for longevity.
Some genes are really ugly. The apoE4 gene,
for instance: currently, individuals who inherit
apoE4 from both parents have virtually 100
percent chance of developing Alzheimer's by
age 80. Another ugly gene is the trinucleotide
repeat mutation of Huntington's Disease,
which being dominant has only to come down
from one parent to confer a horrific fate on the
recipient. We need a lot more research on the
ugly genes, but there's reason to believe that
diet and nutraceutical intervention could at
least delay their clinical impact.
Proteogenomic (protein-gene) and nutrigenomic
(nutrient-gene) research has been
markedly accelerated by recent technological
advances. The results are showing that vitamin
E, alpha-lipoic acid, carotenoids and other
antioxidants have direct effects on multiple
gene sets. Vitamin E has the potential to
regulate genes involved in:
- Glucose metabolism, so essential to our celllevel energy supply;
- Processing of xenobiotics, substances foreign to the body and potentially toxic;
- Biosynthesis of heme, for oxygen transport and carbon dioxide clearance;
- Cholesterol metabolism AND essential fatty acid metabolism;
- Adaptive antioxidant response to free radical challenge (goxidative stressh);
- Cell growth and proliferation; cell death (apoptosis) as appropriate.
Vitamin E has been known to be effective for
circulatory health since the 1950s. Oxidized
LDL (low-density lipoprotein, oxLDL) easily
damages human endothelial (arterial lining) cells
in culture and many experts believe this is an
early step toward atherosclerotic coronary
damage. OxLDL up-regulated many genes, some
of which were down-regulated by vitamin E.
Selenium is a mineral and antioxidant
enzyme cofactor (for glutathione peroxidase).
In rats, selenium deficiency caused a 14x
down-regulation (that is, to 1.14 of the normal
activity) of the gene for this enzyme.
Controlled clinical trials indicate selenium as
the SelenoExcellTM dietary supplement has
great promise in prostate cancer prevention,
perhaps more in combination with vitamin E
as gamma-tocopherol.
Sophisticated DNA microarray technology
can study the workings of 400-plus genes
concentrated in an area one inch square.
Looking at genes from rat liver cells, combined
selenium and vitamin E deficiency caused five
percent of these genes to be up-regulated or
down-regulated. Of their protein products,
certain anti-inflammatory enzymes were
down-regulated, pro-inflammatory proteins
up-regulated. Several key antioxidant and
detoxification enzymes were down-regulated,
while one key cancer-promoting protein was
up-regulated. This pioneering nutrigenic
research is giving tantalizing clues to the clinical
importance of antioxidants.
Also highly active in direct gene regulation
are the omega-3 fatty acids EPA and DHA,
which have a biochemical anti-inflammatory
synergy with the antioxidants. The omega-3s
make cell membranes more efficient and
thereby help optimize energy balance. They
may even promote weight management.
The flavonoids and related polyphenols are
potent antioxidants from plants. Some have
strong capability to influence human genes
(epigallocatechin gallate) from tea has shown
potent, nutrigenic anticancer potential in
many experimental studies.
Other ways the gene environment seems to affect
human gene activity:
- Dietary influences on genes affect all stages of cancer development;
- One gene set similarly influences cardiovascular and osteoporosis risk;
- Subtle gene abnormalities in adipose (fat) tissue may raise diabetes risk;
- Deficiency of the affordable nutrient folic acid increases Alzheimer's risk;
- Physical exercise may activate brain stem cells to replace missing neurons.
What about that character each of us knows,
who obviously is not taking care of himself but
doesn't ever seem to get sick? Sure, some
people do better than others under similar
adverse conditions. Maybe this person is a
perennial optimist (he'd have to be, to continue
smoking this long). Maybe he has a
happy home life, a wonderful life partner and
no financial worries. All these factors are
linked to better health.
Or maybe this man has just been lucky.
Maybe he did get dealt a better genetic hand
than most of us. But does he know this for a
fact? Question for us is, how lucky do we feel?
Do we want to risk it all, hoping we'll get
new livers or hearts laterthe waiting lists are
long right nowor do we cover our bases by
practicing simple preventive measures well
within our control?
We can find out more about our gene
profiles. Many major medical centers and universities
have genetic risk assessment programs
for cancer and other diseases. If one or more of
your parents, siblings, or other close blood
relatives had such a life-threatening disease
early in life, you may want to check for a
program in your area. Consider colorectal
cancer: only five to 10 percent of cases are
strongly genetic, but those with known genetic
risk should be screened starting in their teens.
With 30,000 genes being shuffled from our
parents to us, we all get some bad genes and
some good genes. Probably a few ugly ones as
well. The modern, everyday environment that
confronts our genes causes on average at least
one million DNA damage events per cell per
day. If (big IF) we have good DNA-protective
and repair enzymes and IF we take our antioxidants
and lots of other protective nutrients
and IF we exercise to keep our cells well
supplied with oxygen and glucose, and IF we
were dealt a fighting genetic hand, we have a
shot at long life. It's all about the care and
feeding of our genes.
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