It seems lately that any biometric can inspire a test pitched to consumers, using jargony buzzwords and promises of health, wellness, and longevity. Measuring the length of telomeres, the short DNA sequences at the tips of chromosomes that whittle down as we age, is one such pseudoscience-based offering.
“The DNA test to help you stay younger longer,” and “control how well you’re aging based on your telomere length,” blares one website. Send in a swab and receive “your current telomere length reported as the age of your cells in TeloYears, and the option to work with an expert to develop a personalized lifestyle improvement plan based on telomere science.”
Not surprisingly, Telomere Support supplements are available to help achieve the promised stoppage of time. These include the usual suspects of vitamins and anti-oxidants, plus black tea extract and pygeum extract (from the African cherry tree, used to treat an enlarged prostate). Only $59 a month!
Another company offers to tell the consumer “physiological/biological age” via the mean length of the telomeres, with a deal to test four times a year for $299, to track changes.
I’m not buying any of it.
Yes, diseases can result from abnormal telomere maintenance, but that’s got nothing to do with what the companies are pitching. Two new articles in the Mayo Clinic Proceedings report on 17 patients with short telomere syndromes, while a third article, a commentary, tackles the commercialization of the science, “Telomeres in the Clinic, Not on TV.”
Telomeres aren’t anything new. I wrote about the intriguing history of their discovery in 1995. And Elizabeth Blackburn, Carol Greider, and Jack Szostak received the Nobel Prize for their discovery and description in 2009.
The 194 telomeres in a human cell – 4 telomeres for each of the 46 chromosomes – add up to thousands of DNA bases. Each telomere consists of repeats of the DNA sequence TTAGGG, a 6-letter word shared with all other vertebrates.
At each cell division (mitosis), 50 to 150 of the endmost bases drop away from each telomere, slowly shaving the chromosomes. Mitosis halts, as if adhering to a cellular clock, after about 50 divisions. This abrupt cessation of division is the famous-in-biology-circles Hayflick limit, named for Leonard Hayflick, who reported on the telomere clock back in 1961. Take a cell that’s divided 20 times, freeze it for a few years, thaw it, and it’ll divide about 30 more times. The reawakened cell may carry on but never divide again, or die.
A few types of cells keep their telomeres long – eggs, sperm, and cancer cells. To do so they deploy an enzyme, telomerase, that provides a wonderful example of chemistry becoming biology.
Telomerase consists of protein and RNA, and the RNA part is the sequence AAUCCC, the complement of the DNA telomere unit TTAGGG. The protein is reverse transcriptase, which copies the RNA into DNA, generating new material for the chromosome tips, like adding beads to a necklace.
But most cells don’t produce telomerase and their telomeres shrink in sync to the cell division clock. Telomere shortening is also exquisitely sensitive to environmental stimuli, hastening with chronic stress, obesity, too little exercise, high blood sugar, inflammation, and exposure to toxins or radiation. It makes me wonder if all the political squabbling on social media can shrink telomeres.
Short Telomere Syndromes
In most cell types, a suite of proteins oversees telomere length, preventing the chromosomes from glomming together like sticky spaghetti or becoming so frayed that they trigger DNA repair that can lead to cell death.
A mutation in any of the 13 genes that encodes one of these proteins causes a “short telomere syndrome.” But not all the genes are known. Of the 17 patients described in the Mayo Clinic journal, only six had mutations in genes known to affect telomere assembly, length and stability.
The danger of stunted telomeres is that whittling down the chromosomes too fast “exhausts” the burgeoning stem cell populations that make growth, development, and healing possible. That leaves multiple organ systems with too few cells. Most sensitive are the cell types that normally divide often, such as those of bone marrow and linings (epithelium).
The first short telomere syndromes described were extremely rare single-gene conditions, such as dyskeratosis congenita, a form of bone marrow failure that affects one in a million children. More recently, attention has turned to common conditions that short telomeres might explain. These include deficiency of T and B cells (impairing immunity); digestive problems such as enterocolitis, celiac disease, and a blocked esophagus; lung conditions including early-onset emphysema and idiopathic pulmonary fibrosis (IPF); a form of liver cirrhosis; osteoporosis; abnormal cartilage development, prematurely gray hair; and predisposition to cancers of the blood and epithelia. (The cancers arise in the context of short rather than long telomeres from the compromised immunity.)
The short-telomere syndromes are termed “accelerated aging syndromes,” but the genetics differs from that of the better-known progeria, which causes children to appear elderly. A clinical trial at The Inherited Bone Marrow Failure Precision Genomics Clinic at Mayo is testing how physicians can identify families with short telomere syndromes based on the various associated conditions and going gray before age 30.
The symptoms of the short telomere syndromes also come sooner with each generation, a phenomenon called genetic anticipation. This happens because a person who inherits such a syndrome is born with a double whammy: the product of a sperm and egg that already had stunted telomeres, and the inherited mutation that further speeds the shrinkage.
The techniques used to measure telomeres are like a trip back in time in biotech. They include variations on the PCR theme, the 1980s-era restriction fragment length polymorphism (RFLP) mapping, optical techniques, and the gold standard, flow-FISH (flow cytometry coupled with fluorescence in situ hybridization). Flow-FISH is used clinically to identify patients with short telomere syndromes who could benefit from bone marrow transplantation.
It’s complicated. Each chromosome type has a range of normal sizes for its telomeres, and the overall distribution of lengths for the 23 pairs of chromosomes varies by cell type. (For clinical applications, telomere length is typically assessed in white blood cells.) The tally of chromosome tips that are too short may be more meaningful than overall or average length. For example, just 5 short telomeres out of the 194 in skin fibroblasts can trigger DNA repair leading to cell death. And so the distribution may be more important than the actual overall extent of telomere DNA.
Still, the metric to assess telomere length in an individual is the percentile of the normal range. A person with a short telomere syndrome has telomeres as long as 1% of the healthy population for the same age range.
The ability to analyze telomere lengths and distribution is helping with treatment for people with short telomere syndromes, but that same quantification has made telomeres irresistible targets for direct-to-consumer (DTC) marketing of tests and products.
That’s why Mary Armanios, MD, from the Telomere Center in the McKusick-Nathans Institute of Genetic Medicine at Johns Hopkins University School of Medicine wrote “Telomeres in the Clinic, Not on TV” to accompany the case report and review article in the Mayo Clinic Proceedings. “These products present an oversimplified view of telomere length health: ‘short telomeres are bad’ equitable with aging, while ‘long telomeres are good’ and signify youthfulness,” she warns. Youthfulness of cancer cells, perhaps.
Limitations of measuring telomere lengths are many. The techniques used vary greatly and have poor reproducibility. Plus, DTC tests tend to report only the median or mean value for a patient’s submitted cells, which may only be meaningful for the lower extreme, and doesn’t include the distribution. Dr. Armanios compares this averaging shortcut to the “absurdity of reporting any value that is below the median for a white blood cell count as abnormal.”
In short, telomere lengths are too variable within a population, too variable within an individual, and too sensitive to environmental factors, to offer any reliable information for common disease risk. It also doesn’t appear to be individualized enough for another potential application, forensics.
Say a headless corpse washes ashore. Could measuring the telomeres in cells from a bit of soft tissue clinging to a bone reveal the age, or even age range, of the victim? To test this possibility, researchers in Sweden measured the telomeres in 100 blood donors of a range of ages. Age predictions were off by up to 22 years. People of the same age had widely different telomere lengths. Even the lengths in cheek and blood cells from the same person disagreed. Given the sensitivity of telomere length to environmental factors, these disagreements aren’t surprising.
Even if telomere length could be correlated to specific traits, tendencies, or even future diseases, as the science stands now, that information is useless because longitudinal studies haven’t yet revealed normal ranges over time.
Deja Vu All Over Again
The telomere companies remind me of other “lifestyle” DTC genetic testing companies that offer clueless clients tests of genome-wide gene variants that are meant for basic research into gene discovery, not assessing health in an individual.
These companies pitch me on a regular basis, probably seeking coverage here, and it typically takes awhile for the PR folk to dig far enough to find a researcher who ultimately confirms my query that yes, the test is just a GWAS – genome-wide association study – which can provide only glimmers of tiny risk associations. This company, for example, uses GWAS data to dispense “diet, fitness, and supplement” advice.
Here’s a nice review of how some of these offerings are thinly-veiled attempts to pair useless genetic information with just selling stuff, at hiked prices. The examples are recent. My personal favorite unmasking of DTC genetic testing trickery, though, is from 2006.
In NUTRIGENETIC TESTING:Tests Purchased from Four Web Sites Mislead Consumers, a researcher from the U.S. Government Accountability Office sent two DNA samples – one from a 9-month-old girl and the other from a 48-year-old man – along with 14 made-up lifestyle/dietary profiles of “fictitious consumers,” twelve for the female, two for the male, to four nutrigenetics testing companies. The profiles included age, weight, exercise and smoking habits, coffee consumption, and diet, but nothing about health. The tests probed “a limited number of genes” that affected such things as bone and cholesterol metabolism, mineral absorption, clearing toxins, and “protective systems,” which I assume meant immunity.
The fake people representing the two DNA samples received the same elevated risks: common conditions like osteoporosis, hypertension, type 2 diabetes, and heart disease. But good news! For a fee as high as $1,200, a package of personalized supplements – vitamins and antioxidants, just like the telomere companies – could counter the supposed dire genetic fate, although these aren’t single-gene conditions. The accompanying expert advice was generic and obvious: exercise, stop smoking, eat more veggies. Interestingly, a review of “The Telomere Effect,” co-authored by one of the telomere Nobelists, concludes “Minimize stress, take regular exercise, get enough sleep, don’t smoke and don’t eat too much processed food – this book isn’t going to give you much health advice you haven’t already heard.”
So there’s plenty of precedent for the fallacy of telomere testing to predict anything about future health or longevity. In her editorial Dr. Armanios concludes that such testing “risks causing unnecessary anxiety, with some believing they are ‘biologically aged’ and further leading them to pursue untested products” and warrants “caution against testing (telomeres) in commercial settings.”
I agree with her assessment that telomere length testing is “molecular palm reading,” a modern version of snake oil.