By Joseph M. Raffaele, MD
A telomere, Dr. Oz explained, is like a protective cap for the ends of chromosomes, which carry the genetic material of cells. He took out a shoelace and held up the two ends-one with its plastic tip, the other without. Just as that tip keeps the threads of a shoelace from fraying, telomeres keep our chromosomes intact and functioning-healthy enough to allow them to reproduce cells. Which is, after all, the key to healthy aging. When you can’t reproduce cells,” said Dr. Oz, “you’re old and you’re frail.”
It’s the length of a telomere that’s crucial-the longer it is, the healthier you are. And not surprisingly, the older you are, the shorter your telomeres tend to be. What makes this something other than a sad and inevitable fact of life is the same thing that makes the anti-aging field so dynamic. Over the past few years, researchers have been developing methods to measure telomeres-and to evaluate the beneficial effects of therapies to maintain and even increase telomere length. And that makes it one of the most exciting new areas in the entire field.
Oprah, for one, was impressed. She wanted Dr. Oz to measure her telomeres. He did, and found that they measured up. But if having her telomeres measured seemed exotic, it won’t for long.
It’s been a generation since cholesterol levels became known as a marker of cardiovascular health and mortality itself, reliable enough to become a cultural touchstone: People began comparing their cholesterol counts in general conversation, and cholesterol-reducing strategies from eating less fat to taking medications like Lipitor became a mainstay of any discussion of personal health. But monitoring and intervening in cholesterol levels is now about as cutting edge as a floppy disk.
Though a major advance in its day and still a useful tool, cholesterol counts are hardly sophisticated by today’s standards. It can give you a snapshot of your heart health, but not much more. Whatever your cholesterol count is today, and whatever it might indicate about your risk of heart disease, it tells you nothing about the cumulative damage your arteries have undergone over the years. History is not written in your cholesterol level. So as an early-warning system, it has its limitations. And it’s by no means a biomarker of aging.
But telomere length is-and its time is fast approaching. It won’t be long before people are talking less about their cholesterol counts than about their telomere lengths. Indeed, it’s becoming increasingly evident how closely related the two developments are-and how far telomere length may surpass cholesterol as a diagnostic and therapeutic tool. Just as the original Framingham Heart Study demonstrated a link between high cholesterol and heart disease, many studies over the past few years have made a direct association between telomere length, age, and chronic disease.
However, unlike with cholesterol, it’s not just one of the diseases of aging that is associated with telomere length, but many-everything from cancer to dementia. And just as the world changed when a test to inexpensively measure cholesterol came along, it is about to change again with the development of a simple lab test to measure telomere length that will become increasingly available in the coming few years.
What makes all this mean something is that biotech researchers have not only come up with a way of measuring your telomeres. They have also shown that there are ways of maintaining their length as we age-and even making them longer. Just as Lipitor and similar drugs have been shown to lower cholesterol, published studies have demonstrated the beneficial effects of therapies that lengthen telomeres, and some will soon be on the market.
With cholesterol, it is LDL-the so-called “bad cholesterol”-that’s the culprit in cardiovascular risk. Your total cholesterol count is important only to the extent that it is a biomarker for elevated LDL. The corollary for telomeres is that it’s the shortest ones that tell the story, not the average of them all. But as with total cholesterol being a marker of elevated LDL, if your mean telomere length is short, then your cells are likely to be harboring a greater percentage of critically short telomeres-those that trigger the aging or death of cells so that they can no longer replicate, or make normal cells in some tissues susceptible to transforming into cancerous ones.
Most cells can replicate about 50 times before their telomeres become too short to protect essential parts of the DNA during the replication process. But it’s not the telomeres in all the tissues of the body that are good biomarkers of aging. The ones we need to look at are only those in cells known as leukocytes – immune cells in blood and lymph tissue commonly known as white blood cells. So we now have an important new acronym to add to the list of terms you’ll need to know if you are sophisticated about aging and personal health in general: LTL-leukocyte telomere length (1).
Recent research has established an association between LTL and age-related diseases. In the case of atherosclerosis-the stiffening and narrowing of arteries that is a precursor to heart disease and stroke-leukocyte telomere length has emerged as a much better indicator than cholesterol (2), and a legitimate biomarker of aging.(3) In one striking piece of evidence, researchers using the established method of comparing same-sex twins have found that those with shorter leukocyte telomeres were more likely to die first(4).
Like cholesterol, telomere length has a genetic component but is generally most affected by environmental and lifestyle factors that influence the attacks and strains our cells must withstand over our lifetimes. Smokers and people who are obese, or stressed, or don’t eat healthy or exercise regularly have been shown to have shortened LTL. In fact, every bad habit you can think of shortens telomeres, so it is really an integration of all the risk factors for cardiovascular disease(5). And more.
Research has found that measuring telomeres provides much more information than cholesterol levels about the cumulative oxidative stress and inflammation-the processes that attack and age the cells throughout the body-that an individual has undergone over the years. The brilliance of telomere length as a biomarker of aging is that it is essentially an historical record of the need for white blood cells to divide to fight off infection or tumors, and of the burden of oxidative stress from the cell-damaging molecules known as free radicals. A cholesterol count can’t give us anything like the record of cumulative damage that a telomere measurement can. It’s why you may not necessarily have problems if your cholesterol is high-but you do have problems if your telomeres are short. It’s also why LTL tells us about our risk for nearly all the diseases of aging, not just cardiovascular disease (6). And it’s why young people who have their telomeres measured will have a baseline and a way of tracking how they are aging.
So now you’re wondering how you can have your telomeres measured. A Canadian company, Repeat Diagnostics, was the first to develop commercial testing for telomere length, and Texas-based Spectracell has recently joined the field. For the patient, it’s no different from any other blood work, other than it costs more-around $400 at the moment. But it is a burgeoning field, and testing will become much more widely available, at a lower cost, as others come on the market. One company now ramping up is called Telome Health. It was co-founded by Dr. Elizabeth Blackburn, who won the Nobel Prize in 2009 for discovering how chromosomes are protected by telomeres and an enzyme, called telomerase, that maintains their length.
The next question is: what can be done about short telomeres. Biotech companies are working on compounds that would activate telomerase, building telomeres back up when they get worn down. There is a whole new field looking for potent, safe telomerase activators, and perhaps the most promising so far is a supplement known as TA-65R, a natural substance extracted from an ancient Chinese herb called Astragalus. TA-65R was discovered by the California biotech company Geron, whose researchers screened thousands of natural compounds for telomerase activity. A company called TA Sciences has licensed the rights to offer TA-65R as a nutritional supplement, and it is currently marketed only through specialized medical practices, including PhysioAge Medical Group.
In an observational study of 114 TA Sciences clients, which I was fortunate to conduct at PhysioAge with the eminent telomere biologists Calvin Harley, Maria Blasco and William Andrews, we found that TA-65R decreased the number of short telomeres in the leukocytes of older adults and rejuvenated aspects of their immune systems after just one year of therapy. (The patients took TA-65R, along with a comprehensive regimen of dietary supplements formulated by our practice.) In December 2010, we published our results in http://www.liebertonline.com/doi/pdf/10.1089/rej.2010.1085 Rejuvenation Research (7). In the coming year, TA Sciences will be funding a placebo-controlled study of 1,000 older adults taking TA-65R because our first study yielded intriguing evidence that, by rejuvenating the immune systems of people in their later years, we may be able to add a significant number of quality years to their lives.
So it seems that this is the decade of the telomere. Research confirming the importance of telomeres in aging and disease continues apace, leading to yet more studies and findings. One recent and continuing line of research, for instance, found up to a three-fold increase in breast cancer risk in women with the lowest telomere length on one arm of a particular chromosome (8).
Indeed, researchers seem to be looking everywhere to test the idea that telomeres hold a key to a healthy and long life. It’s axiomatic that married men tend to be healthier and live longer than those who are unattached. One group of researchers in Britain tested 321 men between 40 and 64 and concluded from the results: “Unmarried individuals have shorter telomeres (9).”
That might be merely an amusing tidbit compared with some of the serious work going on, but there seems little question of the wealth of information about disease and aging that can be gleaned by measuring the telomeres in a single, easy blood draw. No doubt, LTL is the new star among the biomarkers of aging-and soon to dethrone cholesterol as the number you need to know.
1. Aviv A. 2009. Leukocyte telomere length: the telomere tale continues. Am J Clin Nutr 89: 1721-2
2. Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, Packard CJ, Samani NJ. 2007. Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet 369: 107-14
3. Brouilette S, Singh RK, Thompson JR, Goodall AH, Samani NJ. 2003. White cell telomere length and risk of premature myocardial infarction. Arterioscler Thromb Vasc Biol 23: 842-6
4. Kimura M, Hjelmborg JV, Gardner JP, Bathum L, Brimacombe M, Lu X, Christiansen L, Vaupel JW, Aviv A, Christensen K. 2008. Telomere length and mortality: a study of leukocytes in elderly Danish twins. Am J Epidemiol 167: 799-806
5. Demissie S, Levy D, Benjamin EJ, Cupples LA, Gardner JP, Herbert A, Kimura M, Larson MG, Meigs JB, Keaney JF, Aviv A. 2006. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 5: 325-30
6. Aubert G, Lansdorp PM. 2008. Telomeres and aging. Physiol Rev 88: 557-79
7. Harley CB, Liu W, Blasco M, Vera E, Andrews WH, Briggs LA, Raffaele JM. 2010. A Natural Product Telomerase Activator As Part of a Health Maintenance Program. Rejuvenation Res
8. Zheng YL, Loffredo CA, Shields PG, Selim SM. 2009. Chromosome 9 arm-specific telomere length and breast cancer risk. Carcinogenesis 30: 1380-6
9. Mainous AG, 3rd, Everett CJ, Diaz VA, Baker R, Mangino M, Codd V, Samani NJ. 2011. Leukocyte telomere length and marital status among middle-aged adults. Age Ageing 40: 73-8