Washington: A new study now finds that an HIV drug significantly reduces age-related inflammation and other signs of ageing in mice. The findings were published on Thursday, Feb. 7, in the journal Nature. The collaborative research project included researchers at Brown, New York University, the University of Rochester, Université de Montréal and the University of Virginia School of Medicine.
Speaking about the study, John Sedivy, said, “This holds promise for treating age-associated disorders including Alzheimer`s," adding, "And not just Alzheimer`s but many other diseases: Type 2 diabetes, Parkinson`s, macular degeneration, arthritis, all of these different things.
That`s our goal." Age-related inflammation is an important component of age-associated disorders.”Sedivy says that the HIV drug acts by halting retrotransposon activity in old cells.Retrotransposons -- DNA sequences able to replicate and move to other places -- make up a substantial fraction of the human genome.
Retrotransposons are related to ancient retroviruses that, when left unchecked, can produce DNA copies of themselves that can insert in other parts of a cell`s genome. The research team found that an important class of retrotransposons, called L1, can escape from cellular control and begin to replicate in both senescent human cells -- old cells that no longer divide -- and old mice. The team tested six different HIV reverse transcriptase inhibitors to see if they could block L1 activity and the interferon response.
One generic HIV drug, lamivudine, stood out because of its activity and low side effects.Growing human cells in the presence of lamivudine did not impact when the cells reached senescence or kill the senescent cells, Sedivy said.
But lamivudine did decrease the interferon response and the late-stage senescence-associated secretory phenotype (SASP) -- the important characteristics of senescent cells that promote inflammation in their neighbours."When we started giving this HIV drug to mice, we noticed they had these amazing anti-inflammatory effects," Sedivy said. "Our explanation is that although L1s are activated relatively late in senescence, the interferon response reinforces the SASP response and is responsible for age-associated inflammation.
"Treating 26-month-old mice (roughly equivalent to 75-year-old humans) with lamivudine for as little as two weeks reduced evidence of both the interferon response and inflammation, while treating 20-month-old mice with lamivudine for six months also reduced signs of fat and muscle loss as well as kidney scarring.
Sedivy is eager to translate the findings to humans. Specifically, he would like begin clinical trials of lamivudine for various age-associated conditions such as frailty, Alzheimer`s disease and arthritis.Lamivudine was approved by the Food and Drug Administration in 1995, has been used to treat HIV/AIDS for decades, and its pharmacological activity and safety are well established, Sedivy said.
He would also like to develop a new reverse transcriptase inhibitor specifically for the L1 reverse transcriptase. To aid in developing a specific therapeutic with minimal side effects, the molecular structure of the L1 reverse transcriptase needs to be determined, he added. Researchers could also develop other types of drugs that target the L1 retrotransposons.