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A new study published in Nature reports that a drug used to treat HIV significantly reduces age-related inflammation and other signs of aging in mice.
"He is promising in the treatment of age-related disorders, including Alzheimer's disease," said John Sedivy, lead author of the study and professor at the University of Ottawa. Brown University. "And not just Alzheimer's disease, but a lot of other diseases: type 2 diabetes, Parkinson's disease, macular degeneration and arthritis – that's our goal. "
Age-related inflammation is an important component of diseases that affect men as they mature.
The researchers discovered how inflammation occurs in old cells (cells that no longer divide). DNA sequences that are able to replicate and move elsewhere are common in the human genome and our cells have evolved to control these "jumping genes", but as we age, a specific sequence, called L1, can "s & # Escape from this control.
In the new study, the research team has shown that replication of L1 DNA copies is detected by an antiviral immune response, which triggers inflammation of neighboring cells.
At the moment the inflammation occurs:
- L1 DNA sequences escape control in old cells and begin to replicate
- Uncontrolled replication of these sequences of cells. DNA triggers an immune system response
- The immune response is the inflammation of neighboring cells
Understanding this, the team discovered the potential mechanism by which these jumping genes can cause inflammation of the cells. cells without necessarily damaging the genome.
L1 DNA sequences require a specific protein called reverse transcriptase to replicate. HIV and other retroviruses also need the same reverse transcriptase protein to replicate and this is where the role of anti-HIV drugs comes into play.
AZT, the first drug released point to treat HIV / AIDS, stop reverse transcriptase of HIV. Multi-drug badtails currently used to treat or prevent HIV / AIDS still contain specific reverse transcriptase inhibitors.
Sedivy and his colleagues thought that this type of drug could prevent replication of L1 and thus prevent the immune response to the cause of inflammation.
As the drug acted:
- "copies" of L1 created from an uncontrolled replication need the reverse transcriptase protein (the same as that required for HIV and d & # 39; other retroviruses) to multiply the anti-HIV drug (19659008). inhibits the action of reverse transcriptase
- without reverse transcriptase, copies of L1 do not reproduce the same way and inflammation decreases
The generic remedy is demarcated
] The team tested six different inhibitors of HIV reverse transcriptase to see if they could block N1 activity and uncontrolled replication. Lamivudine, a generic HIV drug, has been recognized for its activity and low side effects.
"When we started administering this HIV drug to mice, we found that they had these incredible anti-inflammatory effects" – John Sedivy, lead author of the study and professor at Brown University
"Our explanation is that even L1's are activated relatively late in old cells, replication reinforcing the responsible response to age-related inflammation," said Sedivy.
Lamivudine treatment in 26-month-old mice (approximately 75-year-old man equivalent) for only two weeks reduced evidence for interferon response and inflammation. In the 20-month-old mice, lamivudine for six months also reduced signs of fat loss and muscle mbad.
According to the researcher, the results were encouraging, but there is still work to be done.
"If we treat lamivudine, we produce a tangible nick in uncontrolled replication and inflammation, but that does not return to the normal (cell) stage," he said.
"We can solve part of the problem, but we still do not understand the whole problem of aging." The L1 inverted transcripts are at least an important part of this disorder "- John Sedivy, lead author of the study and a professor at Brown University
Sedivy would like to initiate clinical trials of lamivudine on humans for various age-related diseases, such as Alzheimer's disease and arthritis.Lamivudine was approved in the United States in 1995, it is used to treat HIV / AIDS for decades and its pharmacological activity and safety are well established.
"New clinical trials could be simplified and focus on efficacy of lamivudine in the treatment of age-related disorders" the researcher
He would also like to develop a new reverse transcriptase inhibitor specifically for L1 transcriptase.To badist in the development of a specific treatment with minimal side effects, the st Molecular structure of L1 reverse transcriptase has yet to be determined.
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