Living to 100 healthy years

Our genes help us to determine everything from our height to our eye colour to our risk of heart disease stroke and many other unknown diseases. We can today influence these same genes – in the direction of longevity.

There’s no reason that we cannot prolong our life spans to 100 or more with energy and good health, when from our past experience when lifespan was only 60 years not many years ago and today it peaks to 84 in the U.S. and 74 in our own country (Sri Lanka).

If we can prevent heart disease and cancer through genetic manipulations we could easily add another decade into our lives. Some researchers seem to think that we could recover from them faster and better to extend our lives in health.

Rapamycin a new discovery

Rapamycin, also called sirolimus is being used as a coating in coronary stents to prevent re-stenosis in coronary arteries following balloon angioplasty. In a study in 2009, the lifespan of mice fed rapamycin were increased between 28-38% from beginning of treatment, or 9-14% in total increased maximum lifespan. This gives us a clue that treating humans with rapamycin could extend the lifespan. However, it also suppresses the immune system; hence the drug cannot be easily used by humans. Rapamycin is used to reduce the immune system in organ transplants like the kidney and other organs.

Rapamycin was first isolated from bacteria in a soil sample from Easter Island (Rapa Nui).

Target of Rapamycin (TOR)

TOR is a kinase enzyme and stands for “target of Rapamycin”

It is now been used as an anticancer therapy. Normally immunosuppressive therapy increases significantly higher risk of cancer.  There is a lot that we do not understand about aging, cancer and the immune response, and there are a lot of other TOR inhibitors out there being researched into, and there may be more clues in this anti-aging direction.

TOR inhibitors-Rapamycin

Inhibition of the TOR signaling pathway by genetic pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruit flies. However, whether inhibition of TOR signaling can extend lifespan in a mammalian species was unknown till now. However, rapamycin an inhibitor of the TOR pathway extends the lifespan of both male and female mice when fed at a young age. Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. These findings have implications for further development of interventions targeting TOR for the treatment and prevention of age-related diseases.

Alcohol, Longevity and Cancer

David Foster of the Department of Biological Sciences at Hunter College in New York City wrote a paper and published in the journal Cell Cycle, and his findings are remarkable and most welcome. He pointed out that alcohol can inhibit a protein as mentioned above named TOR (Target of rapamycin) and it seems to shorten the lifespan of cancer cells.

Scientists have known for some time that suppressing TOR can extend longevity; Foster says resveratrol and calorie restriction both seem to extend life because they suppress TOR. Foster notes that alcohol can reduce stress, something the authors of the other paper also mention.

But there is of course that one should know too much alcohol can harm your quality of life even as it extends it. As Foster told me, “In principle, higher levels of alcohol would work better, but of course there is a point where there is a tradeoff with liver and behavioral problems.”

Chromosomes and aging- Telomeres

Controversy has long existed in scientific circles as to the precise role of genetics play in the aging process and determination of longevity. Life span seems to be genetically determined. Healthy human cells undergo divisions or replications and terminate into senescent phase. The number of times the cell can divide is determined by its genes. There are also non-genetical influences on cellular aging, such as free radical or oxidative damage, and exposure to radiation.

The field of biological aging has in recent years focused on the part played by DNA contained in human cells called chromosomes. All chromosomes have a protective feather like cap at either end called Telomeres. They can be compared to plastic tips fraying on the end of shoe-laces. Each time a cell replicates (copies) itself the tip of the telomere shortens. Shortening of these telomeres have been linked to a host of age-related illnesses such as heart disease and certain cancers. Many scientists believe that telomeres are the closest we may come to identifying a biological clock, and learning how to stop or turn back that clock. These biological timers (telomeres), at the tips of chromosomes in every cell that carry genetic code may give us a clue how we gradually age.

From birth, every time a cell divide(replicates) the telomeres get shorter and there is evidence that people with shorter telomeres, either because they diminish more quickly may be at higher risk from age-related illnesses. Or, it is possible that those who live for shorter periods are born with shorter telomeres. It is possible that gene variants might show how fast people’s body cells are actually aging. People carrying these variants had a difference in the “biological clock” within each cell

The researchers say in the journal, Nature Genetics, that they looked at more than 500,000 genetic variations across the entire human genome to see which variants cropped up more frequently in people known to have shorter telomeres.

They eventually located a number of variants located near a gene called TERC which, in people carrying them, seemed to be equivalent to an extra three or four years of "biological ageing".

It is possible that genetically susceptible people with gene variants may age even faster when exposed to proven bad environments for telomeres such as smoking, obesity or lack of exercise, and succumb to more age-related diseases, said Professor Tim Spector, from King’s College London.

Proteins that detect diseases and target drug development

Mark Baker, the chairman of proteomics at Macquarie University in Sydney proclaims that proteins were the “machinery of life” and the proteome project launched recently is expected to lead to a new era of personalized medicine.

Proteins within the human cells can reveal the presence of disease and provide new targets for drug development. They can indicate whether a patient will react badly to a medication as well as whether a treatment will be effective.

Protein science

Genes contain the instructions for making a protein, (one protein encoded by each gene), and those proteins will decide in what quantities they are made in healthy tissues and organs. More research is required, done presently by the Human Proteome Organization, to know about this protein encoded genes and soon diseases like cancer may be diseases of the past, by knowing more about these protein’s functions and the studies to unlock the future.

What is Gene therapy?

Research presently by the Human Genome Project will have a blue print that can tell us what genes are responsible for a vast array of human diseases, and Gene therapy is intended to stop many of those diseases in their tracts, and prolonging life of the humans.

Genetic influence on Longevity & Variant Genes

How much of our longevity is determined by our genes is undergoing intensive study. It is observed that parents who live long often have very long-lived children. Variants of Genes that are associated with diseases that shorten human lives have been identified, and include the BRCA1 and BRCA2 genes of breast cancer, and apoB, associated with high blood levels of cholesterol. . Variants of other genes have been associated with longer life spans, and inheriting these increases our likelihood of achieving greater longevity. These "longevity assurance" genes include apoE, ACE, HLA-DR, and PAI-1. New research that studied the genes of sibling pairs of extreme old age also suggests that an additional gene or genes on chromosome four may also confer longevity assurance (information from Health and

In the September issue of Cell Metabolism explains why people who carry specific and common versions of a single gene are more likely to have high cholesterol and to suffer a heart attack. Studies in mice showed that a gene known as sortilin (SORT 1), controls the release of LDL cholesterol from the liver into the bloodstream.

The findings suggest that SORT 1 may be a good target for new cholesterol-lowering drugs.

Omega-3 discovery on age-related diseases

Omega-3 fatty acids found in the body of fish and flaxseed help to keep the arteries flaccid, reduce high blood pressure, and other age-related illness as heart disease. Now research shows that the fish oils will slow cellular age.

Doctors followed 608 San Francisco patients with stable coronary-artery disease and found that those with high blood levels of omega-3 fatty acids had less telomere shortening over the next five years. Telomeres are protective caps at the ends of chromosomes (frequently likened to the plastic tips that keep shoelaces from fraying), and telomere length is increasingly seen as a marker for biological aging — entirely separate from chronological age.

In earlier research, cardiologist Ramin Farzaneh-Far, who led the new omega-3 study, helped show that telomere length can be a predictor of death risk in humans. The new finding is exciting because, he says, "it means that telomere shortening is not inevitable." A good diet may not just keep you healthy. Perhaps it really can keep you young.

Low carb diet versus high carb diet for longevity

Chinese and Japanese people have lower rates of heart disease than the Americans, but they have higher rates of some other diseases such as strokes among Japanese people and high rate of pancreatic and thyroid cancers among the Chinese people. It is also known though these people have lower heart attack rates than the Americans do at the present, they have a higher rate of heart attack than Americans did 100 years ago. What has increased in the American diet since then? Not so much egg and meat consumption, but consumption of sugar, highly processed cereals, hydrogenated vegetable oils, and processed foods in general.

These differences may be due to the “macronutrient balance” referring to ratio of fat/carbohydrates/proteins.

Asian diet- they get the majority of their carbohydrates from rice and vegetables. Vegetables being low GI may be a factor in the reduced rates of heart disease among the Asians. Further, as for rice, while it has a modest impact on blood sugar, it causes a paradoxically low insulin release. Americans are getting the majority of their carbs from white bread (white devil), highly processed cold cereals, potatoes, and sugar, all of which have a sky high impact on both blood sugar and insulin release.

Eat Less, Live Longer?

Restricting calories extends animal life, so doctors want to know if going hungry would help us too. Research at the Cornell University, U.S has found that severely food-restricted lab rats lived twice as long as normal ones and were healthier.

It is possible that slight hunger may act as a mild stressor that makes an organism stronger and resistant to the ills of aging. Among humans it is observed that taking fewer calories slows humans metabolism and some data indicate that humans with a slower metabolism live longer.

"Calorie restriction is pretty much the only thing out there, that we know will not just prevent diseases but also extend maximal life span," says Dr. Marc Hellerstein, a nutritionist at the University of California, Berkeley, who studies the biological effects of fasting.

Staying healthy patiently is advised for those who wish to live 100 years healthily, till further research by the Human Genome Project and other Gene Research Organizations find clues for genetic management and cures of diseases. Hope this article will inspire your wellbeing.

Dr Harold Gunatillake FRCS, FACS-Health Writer

(Next article- Treating Diseases through Genome Therapy without Drugs)

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