AIDS antiretroviral accelerate cellular aging

Antiretroviral cause premature aging of cells, according to results presented at a meeting on lipodystrophy , organized by the National Agency for Research on AIDS and Viral Hepatitis ( ANRS) .
Several studies have described the role of the two main classes of antiretroviral drugs , protease inhibitors (PI) and nucleoside reverse transcriptase inhibitors (NRTIs ) in the mitochondrial toxicity observed in patients infected with the AIDS virus (HIV), which one of the main symptoms is the appearance of lipodystrophy ( defects distribution of lipids ) .

The team of Dr. Jacqueline Capeau , Faculty of Medicine Saint- Antoine in Paris , showed a cellular aging due to antiretrovirals. These results were presented at a meeting organized by the Coordinated Action 22 , the working group dedicated to HIV-associated lipodystrophy , the ANRS .

Although mitochondrial toxicity of antiretrovirals is proven for several years, this work establishes a link between cellular aging and antiretrovirals are a first , according to Dr. Capeau .

The researchers treated mouse cells of adipocyte lineage with multiple antiretroviral agents.

Among five molecules , only one did not result in more signs of cellular aging than placebo.

The other four molecules generated several telltale signs of premature senescence . Researchers have particularly noted a decrease cell proliferation they attributed to the overexpression of several proteins involved in cell cycle arrest , such as p21 and p16 proteins.

Confirming several previous results, INTI result in a loss of synthesis of mitochondrial DNA , known also as a symptom of cellular aging. This alteration is due to the inhibitory action , already described, of NRTIs on DNA polymerase gamma , the enzyme responsible for the replication of the mitochondrial genome.

Treating the cells with the result of defects IP maturation of lamin A, a protein involved in the structure of the nuclear wall . Resulting in an accumulation of pre- lamin A precursor , this anomaly is present in several lipodystrophy but also among people with progeria , a rare form of premature aging of genetic origin.

These two phenomena , laminopathy observed with IP and mitochondrial toxicity of NRTIs, were , according to the researchers responsible for the intracellular production of free radicals they observed . These chemical variations, highly oxidizing , are involved in aging and cellular stress.

Dr. Jacqueline Capeau told Reuters Health that the idea of this research was born as a result of testimony from numerous patients on therapy that express fatigue and " feeling older " .