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".