Researchers have recently identified a DNA region known as VNTR2-1 that appears to drive the activity of the telomerase gene, which has been shown to prevent aging in certain types of cells.
From: Washington State University
July
23, 2021 -- Knowing how the telomerase gene is regulated and activated and why
it is only active in certain cell types could someday be the key to
understanding how humans age and how to stop the spread of cancer.
A
research team headed by Jiyue Zhu, a professor in the College of Pharmacy and
Pharmaceutical Sciences, recently identified a DNA region known as VNTR2-1 that
appears to drive the activity of the telomerase gene, which has been shown to
prevent aging in certain types of cells. The study was published in the
journal Proceedings of the National Academy of Sciences (PNAS).
The telomerase gene controls the
activity of the telomerase enzyme, which helps produce telomeres, the caps at
the end of each strand of DNA that protect the chromosomes within our cells. In
normal cells, the length of telomeres gets a little bit shorter every time
cells duplicate their DNA before they divide. When telomeres get too short,
cells can no longer reproduce, causing them to age and die. However, in certain
cell types -- including reproductive cells and cancer cells -- the activity of
the telomerase gene ensures that telomeres are reset to the same length when
DNA is copied. This is essentially what restarts the aging clock in new
offspring but is also the reason why cancer cells can continue to multiply and
form tumors.
Knowing how the telomerase gene is
regulated and activated and why it is only active in certain types of cells
could someday be the key to understanding how humans age, as well as how to
stop the spread of cancer. That is why Zhu has focused the past 20 years of his
career as a scientist solely on the study of this gene.
Zhu said that his team's latest finding
that VNTR2-1 helps to drive the activity of the telomerase gene is especially
notable because of the type of DNA sequence it represents.
"Almost 50% of our genome consists
of repetitive DNA that does not code for protein," Zhu said. "These
DNA sequences tend to be considered as 'junk DNA' or dark matters in our
genome, and they are difficult to study. Our study describes that one of those
units actually has a function in that it enhances the activity of the
telomerase gene."
Their finding is based on a series of
experiments that found that deleting the DNA sequence from cancer cells -- both
in a human cell line and in mice -- caused telomeres to shorten, cells to age,
and tumors to stop growing. Subsequently, they conducted a study that looked at
the length of the sequence in DNA samples taken from Caucasian and African
American centenarians and control participants in the Georgia Centenarian
Study, a study that followed a group of people aged 100 or above between 1988
and 2008. The researchers found that the length of the sequence ranged from as
short as 53 repeats -- or copies -- of the DNA to as long as 160 repeats.
"It varies a lot, and our study
actually shows that the telomerase gene is more active in people with a longer
sequence," Zhu said.
Since very short sequences were found
only in African American participants, they looked more closely at that group
and found that there were relatively few centenarians with a short VNTR2-1
sequence as compared to control participants. However, Zhu said it was worth
noting that having a shorter sequence does not necessarily mean your lifespan
will be shorter, because it means the telomerase gene is less active and your
telomere length may be shorter, which could make you less likely to develop
cancer.
"Our findings are telling us that
this VNTR2-1 sequence contributes to the genetic diversity of how we age and
how we get cancer," Zhu said. "We know that oncogenes -- or cancer
genes -- and tumor suppressor genes don't account for all the reasons why we
get cancer. Our research shows that the picture is a lot more complicated than
a mutation of an oncogene and makes a strong case for expanding our research to
look more closely at this so-called junk DNA."
Zhu noted that since African Americans
have been in the United States for generations, many of them have Caucasian ancestors
from whom they may have inherited some of this sequence. So as a next step, he
and his team hope to be able to study the sequence in an African population.
In addition to Zhu, authors on the paper
include co-first authors Tao Xu and De Cheng and others at Washington State
University, as well as their collaborators at Northeast Forestry University in
China; Pennsylvania State University; and North Carolina State University.
Funding for this study came from the
National Institutes of Health's National Institute of General Medical Sciences,
the Melanoma Research Alliance, and the Health Sciences and Services Authority
of Spokane County.
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