Telomere is a small piece of DNA at the end of a cell chromosome. Together with telomere binding protein, it maintains chromosome integrity and controls cell division cycle. The length of telomere reflects the replication ability of cells. Every time a cell divides, telomeres shorten a little. Once telomeres are exhausted, cells will enter a state of aging. There is a substance called "telomerase" at the end of telomere, which can slow down telomere shortening.
The Harvard team has mastered the key technology to make telomeres active again. Telomeres are also called the "life clock" of cells, and reversing the clock has become the goal of many researchers. Su Nite agarwal, a team senior researcher from Boston Children's Hospital, said: "Since telomeres were identified, a large number of biotech startups and a large amount of investment have poured in, but in the end they failed. There are no related drugs on the market, the company closed down and a new one came. 」
However, he believes that the team has mastered key technologies and is expected to reverse the cell aging process. Researchers have discovered a small molecule inhibitor of PAPD5, which can restore telomere activity of stem cell model in vitro.
Inhibition of key compounds is expected to reverse telomerase Agarwal has been studying the biology of telomerase for the past decade. As early as 20 15, he and his team discovered a gene called PARN, which plays an important role in telomerase.
In this new study, researchers at Harvard University screened more than 654.38 million known chemicals to find compounds that can protect the health function of PARN. They found that this can be achieved by inhibiting an enzyme called PAPD5, which unlocks PARN and destabilizes telomerase RNA.
Neha Nagpal, the first author of this paper from Harvard Medical School, said: "We believe that by inhibiting PAPD5, we can protect the RNA of telomerase and restore the normal balance of telomerase. 」
It is expected that oral drugs will be introduced in the future to reverse aging. The research team conducted experiments on mice and found that this treatment can restore the telomere length of stem cells without any adverse effects on animals. At present, the team is proving that these small molecules are a safe and effective way to slow down congenital diseases and even aging problems.
Agarwal said: "We imagine that these will become a new class of oral drugs, targeting stem cells all over the body. We predict that restoring telomeres of stem cells will increase the tissue regeneration ability of blood, lungs and organs. 」