Telomere Length and Lifestyle
It is the year 1975. Dr. Elizabeth Blackburn is doing her postdoctoral fellowship at Yale, when she notices something strange about the genome of the protozoan Tetrahymena thermophila: at the ends of each of its chromosomes are long stretches of one particular repeating sequence — CCCCAA, CCCCAA — over and over again. Similar repeating sequences are soon also discovered in other eukaryotes, from slime molds to fungi to humans. Blackburn had discovered what are now called telomeres — literally, Greek for “end part.”
At first glance, the purpose of this repetitive DNA seems mysterious. But something so universal and conserved across diverse species must have a purpose. As it turns out, telomeres exist to compensate for a defect in our DNA replication mechanism. When a eukaryotic cell divides, the molecular machinery we have is unable to duplicate the very ends of each chromosome. Thus, with each round of cell division, our chromosomes shorten ever so slightly. It’s pretty clear how this can become a problem — we certainly don’t want to lose the bits of our DNA that code for essential proteins or tumor suppressor genes. That’s why our genomes have evolved telomeres, which serve a buffer zone of expendable DNA that can be sacrificed to prevent our important genes from being truncated.
Telomeres are not, of course, infinite in length. Frequently dividing cells, such as embryonic stem cells, germ cells, and hair follicles, still require a method to avoid depleting their telomeres. As it turns out, there is a natural enzyme fashioned for that very purpose: telomerase. This enzyme is responsible for elongating telomeres by adding more repeat sequences to the ends of chromosomes. Curiously enough, however, a vast majority of human cells do not express telomerase — it is only found where it is needed. As a result, older individuals have significantly shorter telomeres than newborns do.
Could telomeres then be a ticking time bomb related to human lifespan? It’s well-established that human cells can be immortalized by reactivating telomerase — but that’s only in petri dishes. In terms of whole organisms, scientists aren’t sure. Some studies have found little correlation between telomere length and age across species, while others have demonstrated that telomere extension can reverse signs of aging in mice.
It’s tempting to wonder if reactivating telomerase in adult humans might extend lifespan. This approach, however, has one big problem. Adult cells may have a good reason to not express telomerase: it prevents them from dividing too much. And we all know what happens when cells are allowed to divide without limit — cancer. Indeed, around 90% of cancer cells show elevated telomerase activity. On top of that, scientists have shown that mice with elevated telomerase levels have a higher cancer incidence, thus actually shortening their lifespans (although when the tests were done on cancer-resistant mice, their lifespans did actually increase — now all we need are cancer-resistant humans).
Aging is not the only factor that determines telomere length though — it turns out that lifestyle matters a lot. A study led by Princeton professor Dr. Daniel Notterman found that African-American boys living in the most stressful environments had telomeres that were on average 40% shorter compared to those living in the most caring environments. The study took DNA samples from 2600 nine-year-olds, and looked at several indicators of stress, including family stability, socioeconomic status, and parental education. Although the study didn’t establish any causation, it still supports the notion of early intervention for disadvantaged children. Another group of researchers also found links between telomere length and healthy lifestyle (diet and exercise). These links to stress and environment offer a novel view of telomere biology, and explain why there is so much variation in telomere length from one individual to the next.
“Boys living in the most stressful environments had telomeres that were on average 40% shorter compared to those living in the most caring environments.”
What started off as a curious oddity of the genome has now exploded into a massive area of research. For her discovery of telomeres, Blackburn and two others were awarded the Nobel Prize in Physiology or Medicine in 2009. But the work she started is far from over — scientists will undoubtedly be fascinated for years to come by what a few repeated letters at the ends of our chromosomes can say about us.