Humans age at different rates, as a result of various factors like lifestyle and genetics. Now, a new study from the ENGAGE Consortium suggests that people who age faster are at an increased risk of developing age-related diseases like heart disease, multiple sclerosis, and various cancers. The researchers suggest that the way we age is affected by changes to a part of your chromosomes called a telomere. And it's possible that tinkering with telomeres could lead to rejuvenation therapies.
Biologists have known for some time that aging can be linked to our cellular expiry dates; our cells can only replicate so many times before they start to degrade, the result of increasingly shortening telomere lengths in chromosomes — strands of DNA that are stored in the nucleus of cells.
We’re all born with different telomere lengths, and they get shorter at different rates. Biologists measure this as our rate of ‘biological aging’ as opposed to our chronological age; some 90-year-olds have the same ‘biological age’ as, say, some 80-year-olds.
Hoping to investigate this further, a international team of scientists took to the task of measuring the telomere lengths of 37,684 individuals to see if they could identify the genetic variants responsible for telomere length — and whether those variants could be tied to the risk of various diseases.
No doubt, this was a major study, lasting five years and involving 14 centers across eight countries. It’s part of the ENGAGE Consortium (European Network for Genetic and Genomic Epidemiology), a research project aiming to translate the copious amounts of genetic data that’s pouring into meaningful clinical applications.
The scientists were able to identify no less than seven genetic variants that affect telomere length and were directly associated with specific diseases. Specifically, they linked the variants to several types of cancer, including colorectal cancer. They also connected them to multiple sclerosis, celiac disease — and an increased risk for heart attacks.
To better understand this connection, I spoke to Dr. Preston Estep, the Chief Scientific Officer of TeloMe, Inc., and an expert on genetics and human aging. Specifically, I asked him what biological mechanism could account for the shortening of the telomeres.
“Cell replication shortens telomeres, and telomerase, an enzyme encoded in our genes, makes telomeres longer,” he said. “The overall balance of these two determines length, and typically telomerase levels are low enough to allow gradual shortening with time.”
He says that people vary a lot in both starting telomere length and rate of shortening.
“One very important discovery made by the ENGAGE consortium is that genetic variants that predispose to shorter telomeres and higher disease risk are extremely common,” he told io9. “I'm sure many people are surprised that common and even predominant genetic variants predispose to higher risk of disease and mortality, but we are finding this more often as more high-quality and large-scale studies like the ENGAGE study are published. However, from an evolutionary perspective this is to be expected, since the negative effects of these variants don't occur until later in the post-reproductive phase of life.”
As Estep noted, the telomerase enzyme makes our telomeres longer. This insight, along with the genetic findings of ENGAGE, could mean that rejuvenation therapies might soon be possible. I asked Estep how difficult it is to measure someone’s telomere length and whether or not a clinical application awaits us in the future.
“From our perspective, it is technically easy to measure average telomere length, and more difficult to do a detailed analysis that provides a detailed look at the distribution of telomere lengths from shortest to longest,” he said.
The problem, however, is getting access to testing since all tests to date have been fairly expensive and done on blood.
“Over the past 2-plus years we have developed and refined methods for measuring telomeres in saliva, and for establishing a mail-based saliva collection and processing pipeline,” he said. “That allows us to keep costs low and make telomere testing available to essentially everyone.”
But eventually, says Estep, the testing of telomeres will be very similar to routine cholesterol or blood pressure testing in a number of important ways:
- Dynamic: Telomere lengths change over time and are influenced by both genetics and many lifestyle factors
- Meaningful: Very short or very long telomeres not only are associated with higher risk for disease and mortality, they are a cause
- Treatable: Telomere length can be controlled not only through lifestyle factors, but also through therapeutic means
And in fact, Estep is so serious about this that his company has set up an Indiegogo campaign for introducing people to telomere testing.
In terms of actual approaches, he has some ideas.
“Some weak ones that are already in use are vigorous exercise, stress reduction, good diet — the standard list of positive lifestyle factors,” he told us. “However, people don't respond equally, and those who have very short telomeres might consider more potent means.”
He says that telomerase activator supplements are already being sold, but that people should approach this whole area with great caution.
“I also think that more studies are needed to better understand the benefits and risks,” he added.
“Nevertheless, people with very short telomeres are living with higher risk for many serious health issues, and their best hope for reducing the risk is to fix the problem,” he said. “That isn't a recommendation, it is simply a statement of fact.”
As for the ENGAGE researchers themselves, they’re also hopeful.
"The findings open of the possibility that manipulating telomere length could have health benefits,” noted Dr. Veryan Codd through a statement. “While there is a long way to go before any clinical application, there are data in experimental models where lengthening telomere length has been shown to retard and in some situations reverse age-related changes in several organs."
Read the entire study at Nature Genetics.
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