StemCell Therapy

Inside each of our cells is a genetic hourglass. Every time our cells dividewhich they have to do to keep us alivetheir 23 pairs of chromosomes remain nearly identical. Except for one intentional change: After each division, a cells chromosomes get a little bit shorter.

Ten years ago, a group of scientists won the Nobel Prize in medicine for discovering these ever-shortening DNA sequences at the end of our chromosomes, called telomeres. After a cell has divided a certain number of timesknown as the Hayflick limitits telomeres are so short that the cell knows its time to peacefully shut itself down. When enough cells die off, organs wear out, and eventually, we die, too.

This discovery ushered in decades of aspirational research that set out to understand the role of telomeresand the protein that can rebuild them, called telomerasein aging. Perhaps, if scientists could figure out how to flip our biological hourglasses over, our cells could replicate for longer. Our organs would tire more slowly, and we could delay death.

The Nobel-winning research began way back in the 1970s with the work of biologist Elizabeth Blackburn. But even after four decades, its still not clear if telomeres can safely be manipulated to thwart aging.

That hasnt stopped some scientists from betting on artificially extending telomeres to support longevity: Just last week, Kansas-based biotech startup Libella Gene Therapeutics announced that it would begin early clinical trials testing out a gene therapy that could lengthen telomeres, according to OneZero.

That approach, which as of yet has only been tested in mice, is indicative of humans deep desire to roll back the clock. But the deeper scientists go into the field, the more complicated the story behind telomeres gets: Theres evidence that they may play an important role in other aspects of our health, and that cell division may not be the only reason they shrink over time. Before scientists can try to safely harness telomeres to improve our health, theyll have to answer these questions.

One anti-aging strategy that researchers have investigated involves telomerase, the telomere-building protein that Blackburns colleague Carol Greider discovered on Christmas Day in 1984.

Telomerase is an important tool for cells that divide frequentlylike blood cells, the lining of our digestive systems, or sperm and egg cells. These cells regenerate so often that they need an enzyme to regularly rebuild the caps on the end of their chromosomes.

All the other kinds of cells in our bodies shouldnt have telomerase. But if they did, theoretically, their telomeres would never shrink. They could keep dividing beyond their normal Hayflick limit.

Theres one big problem, though: Cells that have telomerase but arent supposed to often wind up to be cancerous.

In approximately 90% to 95% of cancers, during the process of oncogenesis, telomerase is reactivated, says Masood Shammas, a lead scientist at the Dana Farber Cancer Institute in Boston. As cancer cells spread, theyre able to build their telomeres back upallowing them to keep dividing and dividing and dividing.

This means that messing with telomerase to somehow extend lifeas Libella is attempting to, by injecting patients with a virus containing the gene that codes for telomeraseis risky business.

On the other hand, it also means that blocking telomerase could be a way to treat cancer. Shammas has worked on clinical trials that have tested telomerase-targeting drugs with a company called Geron. Although their original drug worked in mouse models, it failed in early-stage clinical trials for people, because it had some nasty side effects. As a result, scientists have had to put stopping telomerase on hold until they can figure out how to make it only work in cancer cells.

An alternative strategy focuses not on rebuilding telomeres, but slowing their shrinkage in the first place. Scientists are trying to understand what, in addition to normal cell division, causes telomeres to contract. Maybe limiting these activities could decelerate aging in a way that doesnt accidentally reactivate a cancer pathway.

The activities that can slow telomere degradation are still being researched. It seems, though, that theres a lot of daily living that may play a role in telomere length. Anything that damages DNA will damage telomeres, says Shammas.

Telomeres are particularly vulnerable because theyre more exposed on the ends of the chromosomes. Smoking, drinking, and eating red meats fried in oilswhich all produce molecules that can bind to and distort DNAmay harm your telomeres, too. They also happen to all be known carcinogens.

Of course, this doesnt mean their effects are felt immediately, or that these activities will definitely lead to telomere shortening or cancer. Its their cumulative effect over a lifetime, plus other factors that scientists havent nailed down yet, that we need to watch out for. And clinicians generally advise against these activities anyway.

Perhaps more surprisingly, a life-affirming action may also cause telomeres to shrink: Pregnancy.

Dan Eisenberg, a biological anthropologist at the University of Washington, has studied how telomeres behave over time for people who become pregnant. A large cohort study he and his team published last year looked at women in the Philippines. After controlling for age, they found that the more times someone had been pregnant, the shorter their telomeres were. Each pregnancy seemed to shorten a persons telomeres by the equivalent of as many as four years of life.

This could be because of how taxing pregnancy can be on the body. Developing a fetus takes about twice the energy a person normally uses. Theres less energy available to maintain and repair cells for the long-term, Eisenberg says.

While it seems counterintuitive that evolution would penalize a person for reproducing, it may be a necessary trade-off. Perhaps the benefit of spreading new genes into the world is worth the cost of slightly shorter telomeres, Eisenberg explained. After all, evolution doesnt affect the processes that happen to us after we after our reproductive years. Weve already achieved the goal of immortality by way of our progeny.

So, lifestyle modifications to prevent telomere shortening dont sound too appealing. And so far, the only activity that researchers have found that can naturally extend telomeres in the slightest may be exercise. The only thing that world show that can activate telomerase activity is regular exercise, says Shammas. But its still not clear why this is the case, and it certainly doesnt mean that hitting the gym can stave off all aging.

Which brings us back to the promises made by companies like Libella, the gene therapy outfit currently promoting a telomere therapy. With four decades of telomere research yet to produce better guidance than cut down on red meat and exercise more, its easy to appeal to the insecurities and fears of the aging population with less-than-fully-baked treatments.

As OneZero reported, Libellas study is slated to begin early next year in Colombia. Likely, its running there to skirt the US Food and Drug Administrations (FDA) requirement for an Institutional Review Board, which ensures the safety of clinical research participants. Generally, clinical trials overseen by the FDA have been preceded by trials in at least two animal species to show theyre safe and effective. So far, the studies that have backed Libellas gene therapy are based just in mice.

This study has caused a lot of experts to raise eyebrows, particularly when it comes to the ethical issue of asking participants to pay for a therapy with high risks. The company is charging $1 million for each of its five aging but otherwise healthy participants, as well as five participants who have Alzheimers disease and five who have a form of artery disease.

But the trial also raises the question of whether aging itself is a disease worth treating. With any disease, there has to be a disease-free state, says Suresh Rattan, biogerontologist at Aarhus University. In the case of a situation like aging whose main cause is life itself, when will we say that we have treated it? Evolution didnt design us to live forever.

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Science is still studying how telomeres are linked to longevity - Quartz

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