22 March 2011

Fusing aging theories: Telomere shortening causes mitochondrial dysfunction

New research is adding insight and linking three theories of aging—one that suggests telomere shortening governs lifespan, and two others that suggest dysfunctional mitochondria or oxidative stress leads to aging.

At Harvard-affiliated Dana-Farber Cancer Institute, scientists have gathered data suggesting telomere shortening is the cause of mitochondrial dysfunction and diminished antioxidant defenses. Together, they decrease the body’s energy and diminish organ function, both characteristic of old age.

As telomeres—protective caps at the end of cell chromosomes—shorten with age and begin to fray, cells activate the p53 gene, which signals an “emergency shutdown” chain of events that turns off normal cell growth and division and compromise antioxidant defenses. Going one step further, data from the carefully orchestrated mouse study, published in Nature, show that the p53 gene also represses PGC1-alpha and PGC1-beta. These PCGs are considered the master regulators of metabolism and mitochondrial function.

Repressing PCGs increases the number of dysfunctional mitochondria (with mutated mitochondrial DNA) and leads to a decrease in functional mitochondria distributed throughout in muscles and organs. The dysfunctional mitochondria in aged tissues leak greater amounts of reactive oxygen species and the lack of functional mitochondria hinders normal energy production from cell respiration (the body’s main producer of ATP energy).

“What we have found is the core pathway of aging connecting several age-related biological processes previously viewed as independent from each other,” said Ronald A. DePinho, M.D., a cancer geneticist and senior author of the paper, in a press release.

“Because telomere dysfunction weakens defenses against damage by free radicals, or reactive oxygen species,” Dr. DePinho said, “we think this exposes telomeres to an accelerated rate of damage which cannot be repaired and thereby results in even more organ deterioration. In effect, it sets in motion a death spiral.”

In an article also published in the same issue Nature, Daniel P. Kelly, M.D., scientific director and professor at Burnham Institute for Medical Research-Lake Nona, Orlando, Florida, said that the “intriguing study… unveils a potentially unifying mechanism for cellular ageing.”

Mitigating the Toll of Aging

The new study further supports current thinking that the best defense against aging is to reduce the adverse affects of overproduction of free radicals produced from dysfunctional mitochondria, which cause additional oxidative stress.

Dr. DePinho said, “The findings bear strong relevance to human aging, as this core pathway can be directly linked to virtually all known genes involved in aging, as well as current targeted therapies designed to mitigate the toll of aging on health.”

Those current targeted therapies include boosting the human body’s antioxidant defenses by eating a healthy diet, reducing calories (by around 25 percent), and supplementing with antioxidant vitamins C and E, as well as with green tea, CoQ10 and resveratrol. These practices not only help to protect against oxidative stress, thereby protecting against telomere shortening, but also help boost generation of new, healthy mitochondria.

When we asked telomere biologist Bill Andrews, Ph.D., to comment on the new study, he answered that it was “tremendous news,” as it supports the need for more research into management of telomeres by activating the genetic expression of the enzyme telomerase, which re-lengthens telomeres.

Dr. Andrews wrote, “It’s the best support ever for the fact that telomere elongation’s role in aging far exceeds the roles played by mitochondria and oxidative stress.” In effect, telomere shortening is the root cause of the others.

Mitochondria become dysfunctional when telomeres shorten and fray, a new study suggests. In an article to be published in a forthcoming issue of IsaNews magazine, Dr. Andrews writes, “Mitochondrial dysfunction causes aging—but telomere shortening has turned out to be the primary cause of mitochondrial dysfunction. And humans’ natural defenses against oxidative stress are really quite exceptional (for example, our cells produce ten times more superoxide dismutase, a potent natural antioxidant, than mice)—until telomere shortening begins to degrade those defenses inside our bodies.”

He added that while “anti-aging therapies of years past merely treated the symptoms of aging. New research is devoted to identifying a new class of therapies that treat aging at its root cause, and hold great promise of one day allowing us to feel young and healthy at 120 years of age and beyond.”

An earlier study, of which Dr. DePinho was also the senior author, gives testimony to the benefits of telomerase, as found in mice that were genetically engineered to produce the enzyme. The study found that when the telomerase was restored in the mice, their age-related symptoms disappeared and several organs including the brain were rejuvenated.

References:

Kelly DP. Cell biology: Ageing theories unified. Nature 2011;470:342-3.

Sahin E, Colla S, Liesa M et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 2011;470:359-65.

Sahin E, DePinho RA. Linking functional decline of telomeres, mitochondria and stem cells during ageing. Nature 2010;464:520-8.

Jaskelioff M, Muller FL, Paik JH et al. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature 2011;469:102-6.

16 March 2011

Potassium iodide: Why you should avoid it

Ever since the news of Japan's nuclear crisis, there have been several claims made over the Internet that have panicked people in the U.S. about potential exposure to radiation (one culprit is this viral e-mail), which has led to me being the recipient of questions about whether or not people should be taking potassium iodide supplements to avoid absorption to radioactive iodine.

Should you take potassium iodide pills? My answer has been an unequivocal, "No, it's not necessary. There is little risk of any level of radiation exposure to worry about anywhere else other than in Japan near the reactors. If you're worried about getting cancer, try thinking more about losing weight, eating more dietary fiber, and eating more fruits and vegetables."

In the process of answering questions, I did find myself interested in learning more about radiation and health. By far the best, most in-depth article I've read on "How Radiation Threatens Health" is this one written by Nina Bai and published by Scientific American. Bai's article gives readers an excellent understanding on the typical radiation levels that people are currently exposed to (0.2 to 0.3 milliSieverts), how much they are exposed to by a typical CT scan (1 milliSievert) and what kinds of levels people should really be worried about—the kind of levels that lead to symptoms of radiation sickness ("a whole body dose of 3 sieverts, that is, 3,000 times the recommended public dose limit per year") and the kind that kills people within weeks (5 to 10 sieverts).

Yes, there are concerns over low-dose radiation over time, but as Bai's article points out, the increase of cancer risk is small and basically comes out to about an increase of eight potential cancer cases per 10,000 people. And, the point is that even if any radiation made it over the ocean and to the U.S. (which is unlikely) it would be at levels too low to cause concern.

As for potassium iodide (KI) supplements (not addressed in Bai's article), there is cause for concern because I keep reading that these are "flying off the shelves" in various articles.

The way KI works is by flooding iodine into the thyroid gland to become trapped by the thyroid's receptors, which blocks the uptake and accumulation of radioiodine that could lead to possible thyroid diseases or cancer. This is particularly important in children who are more at risk for radioiodine-induced cancer (as is what happened with the Chernobyl incident because of radioiodine0contaminated milk). The doses for preventing radioidine uptake are high: 50 to 100 milligrams for adults. If exposure is pretty certain, then supplementation with these pills make sense.

But consider that the Upper Limit for adults is 1.1 milligram per day. These pharmacologic doses could be potentially detrimental since excessive iodine can actually lead to hyper- or hypothyroidism and have been known to increase risk of thyroid cancers. Taking these doses should not be considered a safe precautionary measure, as marketed. There is a risk!

My concern is this: that the irresponsible Internet claims are leading people to actually take the high doses of the KI and that retail outlets selling them (like this one with 130 milligram per tablet!) are doing so without giving people any sense of what the risks are when taking high amounts.

02 March 2011

Vitamin K2: Building bones while beating back arterial calcification

Vitamin K2's time to shine has come—move over vitamin D! Once only known for its role as a "koagulation" factor in blood clotting, vitamin K2 is emerging as another fundamental anti-aging nutrient. While vitamins D and E have garnered the majority of interest in the last decade, the impact of vitamin K2 on aging bones and hearts demands that we give it equal attention.

Whereas most vitamin and mineral supplements use vitamin K in its form of K1 (phylloquinone sourced from plants) because it is easily available and cheap, it is the natural form of K2 (menaquinone sourced from friendly bacteria) that is the most biologically active and shown to enhance both bone formation and vascular health.

The full compilation of recent research underscores the idea that K1 and K2 should be appreciated as separate nutrients with distinct physiological actions and benefits. K1 is the more familiar vitamin known for its key role in directing blood-clotting in the body and the one given as a shot at birth (a common practice in many countries to curtail hemorrhage incidents in newborns.) The picture for K2 seems to be a bit more varied and is key in regulating calcium balance.

Vitamin K2 acts by activating the bone-building hormone (carboxylating osteocalcin) to clear calcium from the arteries and use it in bone mineralization. It effectively removes calcium that would otherwise end up deposited in arterial plaques. Since protecting arteries and soft tissues from calcification is one of the most important ways to stave off the ravages of aging on the body, consuming enough vitamin K2 daily is key for a long, healthy life.

Getting Enough K2

Because vitamin K2 is synthesized by friendly bacteria in the intestine, nutrition scientists have long assumed that that deficiencies were rare. However, new data are showing that intestinally synthesized vitamin K is not absorbed as easily as previously thought. Vitamin K also preferentially accumulates in the liver where it does have a clotting factor role.

In fact, once overlooked because "time to clot" was the test for vitamin K status, it is here where we are now seeing new signs of vitamin K deficiency previously only seen with vitamin D deficiency—fragile, brittle bones and increased fractures—even with adequate calcium and vitamin D.

Most people in North America should increase amounts consumed daily. The evidence finds that only with much higher intake do bone cells get their share and the same holds true for removal of calcium in arteries.

People can obtain enough vitamin K2 by eating plenty of fermented foods such as cheese, sauerkraut, and natto (a traditional Japanese soy-based food). Supplementation is another viable option as achieved with a quality multivitamin.

Regardless of how one gets it, it’s important not to underestimate value of this underdiscussed nutrient and to understand that most people are not getting enough. Consuming sufficient amounts of K2 along with a healthy diet will increase odds of a healthier life with clear arteries and stronger bones.

Sources

McCann and Ames. Vitamin K, an example of triage theory: is micronutrients inadequacy linked to diseases of aging?. Am J Clin Nutr 90:889-907, 2009.
Vitamin K2. Monograph. Alternative Medicine Review 14(3):284-293, 2009.
Koitaya. Et al. Effect of low dose vitamin K2 (MK-4) supplementation on bioindices in postmenopausal Japanese women. J Nutr Sci Vitaminol. 55:15-21, 2009.
Gast, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovas Dis 19:504-510, 2009.
Shea, et al. Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am J Clin Nutr 89: 1799-1807, 2009.
Shea MK, Booth SL Update on the role of vitamin K in skeletal health. Nutr Rev 66(10):549-57, 2008.