A new procedure can quickly and efficiently increase
the length of human telomeres, the protective caps
on the ends of chromosomes that are linked to aging
and disease, according to scientists at the Stanford
University School of Medicine.
New research in The FASEB Journal suggests
thatdelivering modified mRNA encoding the protein
telomerase reverse transcriptase (TERT) to cells
extends their telomeres a finite but significant
amount.
One of the key aspects of aging is the shortening
of telomeres over time. Telomeres, which serve as
protective "end caps" for chromosomes, help keep DNA
healthy and functioning as it replicates.
Unfortunately, these protective end caps become
shorter with each DNA replication, and eventually
are no longer able to protect DNA from sustaining
damage and mutations. In other words, we get older.
Skin cells with telomeres lengthened by the
procedure were able to divide up to 40 more times
than untreated cells. The research may point to new
ways to treat diseases caused by shortened telomeres.
In young humans, telomeres are about 8,000-10,000
nucleotides long. They shorten with each cell
division, however, and when they reach a critical
length the cell stops dividing or dies. This
internal "clock" makes it difficult to keep most
cells growing in a laboratory for more than a few
cell doublings.
"Now we have found a way to lengthen human telomeres
by as much as 1,000 nucleotides, turning back the
internal clock in these cells by the equivalent of
many years of human life," said Helen Blau, PhD,
professor of microbiology and immunology at Stanford
and director of the university's Baxter Laboratory
for Stem Cell Biology. "This greatly increases the
number of cells available for studies such as drug
testing or disease modeling."
The newly developed technique has an important
advantage over other potential methods: It's
temporary. The modified RNA is designed to reduce
the cell's immune response to the treatment and
allow the TERT-encoding message to stick around a
bit longer than an unmodified message would. But it
dissipates and is gone within about 48 hours. After
that time, the newly lengthened telomeres begin to
progressively shorten again with each cell division.
The transient effect is somewhat like tapping the
gas pedal in one of a fleet of cars coasting slowly
to a stop. The car with the extra surge of energy
will go farther than its peers, but it will still
come to an eventual halt when its forward momentum
is spent. On a biological level, this means the
treated cells don't go on to divide indefinitely,
which would make them too dangerous to use as a
potential therapy in humans because of the risk of
cancer.
"This new approach paves the way toward preventing
or treating diseases of aging," said Blau. "There
are also highly debilitating genetic diseases
associated with telomere shortening that could
benefit from such a potential treatment."
For more information
Stanford Medicine
The FASEB Journal
Transient delivery of modified mRNA encoding TERT
rapidly extends telomeres in human cells
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