Yale Medicine is conducting research that may help uncover the secrets to living longer. Yale Medicine pathologist Sandy Chang, MD, PhD, leads research into telomeres, which are made of repeating nucleotide sequences and form a protective cap at the end of chromosomes. In his lab, Chang is exploring the role that telomeres play in how we age and how cancer spreads. The research could lead to a new understanding of both.

"Telomeres are repetitive DNA sequences and proteins that cap the ends of human chromosomes,” Dr. Chang says. “They are synthesized by the enzyme telomerase, but protected by a complex of six proteins call the shelterin complex. Telomerase and shelterin serve to maintain and protect telomeres, respectively...Think of telomeres as little plastic caps at the end of shoelaces and how you can thread a shoelace that has this plastic cap. When there is no cap, the shoelace frays and is no longer functional." 

Similarly, he says, when telomeres become frayed—either because these shelterin proteins become mutated, or the telomeres are critically shortened due to deficiencies in telomerase—they are no longer functional, leading to adverse cellular consequences.

Cancer cells have high levels of the enzyme called telomerase, which "allows cancer cells to grow fast and out of control," Dr. Chang says. "Telomeres in somatic cells, meaning normal cells that are not reproductive cells, lack telomerase and therefore shrink. Yet most cancer cells (and stem cells, meaning cells from which a variety of other cells can develop) have telomerase, which keeps telomeres long and enables the cancer cells to replicate indefinitely."

"My lab at Yale Medicine studies how shelterin proteins bind to telomeres and protect them,” Dr. Chang says.

Interestingly, many common human cancers including melanomas and lung cancers have mutations in POT1. "One day, repairing these mutations in affected patients could lead to lifespan extension and delay the onset of cancer,” he says.

"Ours is the only lab at Yale Medicine spending 100 percent of our research efforts working on telomeres,” he says, “and we are trying to understand the basic mechanisms of how shelterin components prevent telomeres from engaging in a DNA damage response which could initiate aging and cancer."

Though research remains in the early stages, if researchers find a way to preserve, or even grow, telomere length, then this treatment could have profound impacts on how humans age and their susceptibility to disease in older age.