Study sheds light on how increased age is linked to disease

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Photo Credit: Albert Lee | Daily Texan Staff

A study by UT Southwestern Medical Center researchers provides insight into why people are more susceptible to cancer as they age.

According to the study, which was published on Dec. 15 in PLOS Biology, the turning on of a certain gene as someone ages may play a role in the development of cancer.

Inside cells, DNA is packaged into structures called chromosomes, which contain all of an individual’s genetic information. The ends of chromosomes contain non-coding sections of DNA known as telomeres. These telomeres’ job is to protect the chromosomes from damage and from being fused with other chromosomes. Each time DNA replicates, telomeres are shortened a little bit.

“Due to the way DNA replicates, (chromosomes’) ends get shorter and shorter,” said Jerry Shay, professor of cell biology at UT Southwestern. “People believe that eventually, when the ends (of chromosomes) are really short, cells can no longer divide and that may be an important component of aging.”

An enzyme called telomerase adds DNA bases back onto telomeres, a process which makes sure the chromosomes don’t get too short throughout replication. However, telomerase is typically active only for the first three to four months of human development. After this point, the enzyme becomes silenced, unless tumor development occurs in the body. In over 90 percent of human cancers, cancer cells use telomerase to continuously divide and potentially spread the cancer throughout the body.

“There are a lot of genes that are on during human development that get silenced and then turn back on during cancer,” Shay said. “The question is, what regulates telomerase?”

Researchers found that when cells are young and telomeres are still long, the telomere silences TERT, which is the gene that codes for telomerase. According to the study, this effectively stops the process of making telomeres longer. 

However, as cells mature and telomeres become shorter, TERT and genes near it are sometimes expressed differently, said Andrew Ludlow, postdoctoral researcher at UT Southwestern. Ludlow said as humans age and telomeres shorten, telomerase may be reactivated and help cancer cells spread.

Although scientists do not yet know all of the functions of telomeres, they may help explain other biological mechanisms. Shay said one example is that telomere length could be responsible for what triggers the hormonal changes that come with puberty.

“When you’re young, let’s say genes are silenced and you become a teen and go through puberty,” Shay said. “What turns on hormones? Nobody has a clue. An elegant possibility would be that when telomeres on a particular chromosome reach a certain length when you’re a teen, some gene becomes activated because the telomere gets shorter and that could then turn on hormones and lead to puberty.”

In addition to cancer, shorter-than-normal telomeres are associated with a host of other diseases, such as pulmonary fibrosis, which causes lung scarring and breathing problems, and types of aplastic anemia, Ludlow said.

Shay said scientists will need to look further into how the length of telomeres affects how genes are expressed. 

“We think this is the tip of the iceberg, where there may be other genes close to chromosome ends that are regulated by telomere length,” Shay said.