The NR4A nuclear receptors as potential targets for anti-aging interventions.

The development of innovative anti-aging strategy is urgently needed to promote healthy aging and overcome the occurrence of age-related diseases such as cancer, diabetes, cardiovascular and neurodegenerative diseases. Genomic instability, deregulated nutrient sensing and mitochondrial dysfunction are established hallmark of aging. Interestingly, the orphan nuclear receptors NR4A subfamily (NR4A1, NR4A2 and NR4A3) are nutrient sensors that trigger mitochondria biogenesis and improve intrinsic mitochondrial function. In addition, NR4A receptors are components of DNA repair machinery and promote DNA repair. Members of the NR4A subfamily should also be involved in anti-aging properties of hormesis since these receptors are induced by various form of cellular stress and stimulate protective cells response such as anti-oxidative activity and DNA repair. Previous studies reported that NR4A nuclear receptors subfamily is potential therapeutic targets for the treatment of age related disorders (e.g. metabolic syndromes, diabetes and neurodegenerative diseases). Consequently, we propose that targeting NR4A receptors might constitute a new approach to delay aging and the onset of diseases affecting our aging population.