By Dr. Mercola

Telomeres were first discovered in the 1930s. Every cell in your body contains a nucleus, and inside the nucleus are the chromosomes that contain your genes. The chromosome is made up of two “arms,” and each arm contains a single molecule DNA, which looks like a string of beads made up of units called bases.

A typical DNA molecule is about 100 million bases long. It’s curled up like a slinky, extending from one end of the chromosome to the other. At the very tip of each arm of the chromosome is the telomere. In 1973, Alexey Olovnikov discovered that telomeres shorten with time because they fail to replicate completely each time the cell divides. Hence, as you get older, your telomeres get increasingly shorter.

If you were to unravel the tip of the chromosome, a telomere is about 15,000 bases long at the moment of conception in the womb. Immediately after conception your cells begin to divide, and your telomeres shorten each time the cell divides. Once your telomeres have been reduced to about 5,000 bases, you essentially die of old age.

In 1984, Elizabeth Blackburn, Ph.D., professor of biochemistry and biophysics at the University of California, San Francisco, discovered that the enzyme telomerase has the ability to lengthen the telomere by synthesizing DNA from an RNA primer.

She, along with Carol Greider and Jack Szostak, were jointly awarded the Nobel Prize in physiology or medicine in 2009 for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase. Telomere lengthening is now thought to be a major key that explains the process of aging and holds the promise of not just slowing aging, but actually reversing it.

Aging as a Disease

Molecular biologist Maria Blasco, Ph.D., director of the Spanish National Centre for Cancer Research and head of the Telomeres and Telomerase Group,1 is another scientist who ascribes to the idea that aging is the foundational disease that needs to be addressed if you want to prevent degenerative and chronic diseases such as cancer.

In 2008, Blasco set out to determine whether lengthening telomeres will in fact slow aging. To do this, she injected the enzyme telomerase into mice. The result? The treated mice lived on average 40 percent longer than normal. “Of course, it was an amazing feeling,” Blasco says, “because I realized that I had manipulated one of the basic mechanisms for why we age, and this could lead to important applications in the future.”

There was a catch, however. The therapy “would almost certainly have increased the cancer rate in mice, had they not been genetically modified to be cancer resistant,” the narrator notes. And humans cannot, at present, be genetically modified. To address this problem, Blasco and her team further refined the process, and in 2012 carried out a second experiment.

This time, the treated mice lived about 20 percent longer and cancer, when it occurred, was delayed. Still, this does not mean telomerase can or will produce identical effects in humans.

The Epigenetic Clock

Steve Horvath, Ph.D., professor of human genetics and biostatistics at UCLA David Geffen School of Medicine in Los Angeles,2 believes science is still in its infancy when it comes to understanding aging. “I believe there’s a passive clock that measures the state of your cells,” he says. “It doesn’t cause things to deteriorate, it just keeps track of the mechanism that actually does cause that.”

This passive clock mechanism — the epigenetic clock — is something we still know virtually nothing about, but Horvath believes it’s a major player, and in order to be able to prevent aging, we have to understand how epigenetic changes within the DNA molecule affect its biological age.

He’s convinced it is these epigenetic changes that are the root cause of aging, and the good news, should this be true, is that they’re reversible. So, in principle, at least, you can devise treatments to reverse epigenetic changes that drive biological aging within the DNA.

According to Horvath, the telomere theory of aging “has been disappointing.” While many in the antiaging field are enamored with the idea that overexpressing telomerase will lead to aging reversal, the downsides are considerable, because “if you overexpress telomerase and end up with longer telomeres, you actually increase your risk for cancer,” he says. So, while telomere length is part of the equation, he does not believe it’s the answer we’re looking for.

Antiaging — ‘An $8 Billion Industry of Stuff That Doesn’t Work’

According to scientist and entrepreneur Joe Betts-Lacroix, the antiaging business is “an $8 billion industry of stuff that doesn’t work.” He believes the key to longevity is the prevention of degenerative disease, and were you to find something that actually helps prevent multiple degenerative diseases, then you could transfer billions of dollars from each of those disease fields into the antiaging field. As founder of Health Extension, Betts-Lacroix has raised more than $30 million from venture capitalists in search of a cure for aging.

Combined, the scientists and companies under the Health Extension umbrella have raised more than $200 million. Much of this funding is coming from the tech industry, which has become increasingly interested in biology and cracking the biological code. Betts-Lacroix notes that in recent years, scientists have made remarkable discoveries; finding a number of ways to extend life span in mammals. Now, we’re right on the precipice of bringing it into the human realm, which is the most challenging venture of all.

Promising Findings in Animals

One of the findings from animal research is that smaller mammals live longer than larger ones. For example, the smaller the horse, the longer its life span. This, they’ve found, is due to hormones that not only affect life span, but also size. When these hormones are suppressed for life, the animal will be small and live long. When suppressed in adulthood, they’ll retain their regular size, but will live longer than normal.

“As far as we know, for every species we’ve tested, turning down this hormone system extends life span,” says Cynthia Kenyon, Ph.D., vice president of aging research at Calico Life Sciences, a biotech company owned by Google.3 Kenyon made her mark in the field with her studies of the roundworm caenorhabditis elegans in the early ’90s. By partially disabling a single gene, DAF-2, the life span of this tiny nematode was doubled.

“In one fell swoop, the animal lived twice as long,” she says. “That was really stunning, because that was not supposed to happen.” Even more remarkable, other researchers have duplicated the findings on other animals, from fruit flies to mice. Kenyon also notes the research indicates that when you extend life span, you also typically delay degenerative diseases, and when they occur, they’re milder.

As many others, by targeting aging, she envisions a therapy, perhaps a drug, that with one pill can delay or prevent the onset of many diseases all at once.

Research Targeting Senescent Cells

At Unity Biotechnology,4 they focus on another aspect of aging — senescent cells. Cellular senescence is when a cell ceases to divide. In a cell culture, a fibroblast cell can divide a maximum of 50 times, after which it becomes senescent or nondividing. Senescent or nondividing cells also play a significant role in the aging process.

At Unity, researchers were able to remove senescent cells in mice, to observe what would happen. “When we did this, something astonishing happened,” cofounder Nathaniel David, Ph.D., says. The mice had a “profoundly extended health span,” meaning the period of time in which the animals remain healthy and disease free.

The health and function of a number of vital organs were improved, including their hearts and bones, with less heart disease, arthritis, cataracts and other “normal” problems of aging. Soon, Unity will perform its first human trial on patients with osteoarthritis.

Can Diabetic Drug Boost Longevity?

While most researchers are focusing on the creation of new drugs to combat aging, some are focusing their attention on an old one — metformin, commonly prescribed to Type 2 diabetics. It’s been noted that diabetics taking metformin tend to live longer than diabetics taking other diabetes drugs. They also have a lower prevalence of other age-related diseases, including cancer and Alzheimer’s.

Some nondiabetic people are even taking metformin just for its potential antiaging benefits. While metformin is among the least hazardous drugs out there, it does have some serious downsides such as impairing the use of the important vitamin B12.

It is thought to work via AMP-activated protein kinase (AMPK), which plays a vital role in inhibiting glucose production in the liver (gluconeogenesis). AMPK is a conserved sensor and regulator of cellar energy balance that is activated when the cellular AMP-to-ATP ratio exhibits a large increase due to conditions such as nutrient deprivation or pathological stress.

There are far safer alternatives like the supplement berberine that has been shown to have many of the same effects. It is in my view, a better alternative. Berberine has antibacterial, anti-inflammatory, antiproliferative, antidiarrheal, antineoplastic, antidiabetic and immune-enhancing5 properties, and has a long history of use in traditional medicine, including traditional Chinese medicine.

Berberine even helps combat metastatic stem cells and heart failure. Many integrative health practitioners swear by it as a general health supplement due to its ability to address such a wide variety of maladies. It actually works as well as or better than some drugs for certain ailments.6 For example, it’s been shown to improve blood lipids better than statin drugs, and lower blood pressure as well as antihypertensive drugs.

Like metformin, many of berberine’s health benefits7 have been linked to its ability to activate AMPK.8,9 AMPK is an enzyme inside your body’s cells. It’s sometimes referred to as a “metabolic master switch” because it plays an important role in regulating metabolism.10 Low AMPK has been linked to insulin resistance, mitochondrial dysfunction, obesity, neurodegeneration and chronic inflammation — all of which lay the groundwork for a wide variety of serious chronic diseases.

AMPK is also an important neuroprotector. As explained in the Journal of Neurochemistry,11 “AMPK senses metabolic stress and integrates diverse physiological signals to restore energy balance. Multiple functions are indicated for AMPK in the [central nervous system] …” Berberine also benefits brain health and psychological well-being by increasing key neurotransmitters.

Your Lifestyle Is Your Longevity Switch

If there’s ever a pill that will ensure extended youth, everyone will likely want it. The question is whether or not such a thing is even possible. The fact of the matter is, your lifestyle and the choices you make every day play an incredible role in how you will age, and I doubt a drug will ever be devised that will allow you to be a junk food-eating couch potato and still age in reverse. Of crucial importance is keeping your mitochondria healthy, and lifestyle strategies such as diet and exercise are key for this.

Science clearly shows a cyclical ketogenic diet high in healthy fats and low in net carbs promotes healthy mitochondrial function. A number of other strategies are also known to boost mitochondrial health, and I discuss several of them in my book, “Fat for Fuel.” Research also shows you can slow down telomere shortening with exercise.12 It basically buffers the effect of chronic stress on telomere length, which helps explain some of its well-documented effects on health and longevity.

Other studies have found there’s a direct association between reduced telomere shortening in your later years and high-intensity-type exercises. As noted in a study published in Mechanisms of Aging and Development:13

“The results of the present study provide evidence that leukocyte telomere length (LTL) is related to regular vigorous aerobic exercise and maximal aerobic exercise capacity with aging in healthy humans. LTL is not influenced by aerobic exercise status among young subjects, presumably because telomere length is intact (i.e., already normal) in sedentary healthy young adults.

However, as LTL shortens with aging it appears that maintenance of aerobic fitness, produced by chronic strenuous exercise and reflected by higher VO2max, acts to preserve LTL … Our results indicate that LTL is preserved in healthy older adults who perform vigorous aerobic exercise and is positively related to maximal aerobic exercise capacity. This may represent a novel molecular mechanism underlying the “anti-aging” effects of maintaining high aerobic fitness.”

Source link