Expression and regulation of Pax6 in brain of aging mice

Abstract

Aging, an inevitable complex phenomenon among organisms, exhibit progressive loss of functional anatomy but understanding on molecular mechanisms of aging remains elusive. This report presents analysis of complex network of genes and proteins, their functional cascades and hierarchy, and regulation of regulators like Pax6 (Paired box 6) because symptoms of age-associated changes match with patients having mutation in Pax6. The Pax6 has been observed in the olfactory bulb, amygdala, thalamus, and the cerebellum. It is pro-neurogenic in adult neural progenitors and specifies neuronal subtypes in developing brain and the adult. During aging in brain, the reduction in Pax6-positive cells indicates loss of neurons and affects on adult neuronal stem cells. The alteration in co-localization of Pax6, p53 and SPARC may lead to the loss of plasticity, and p53 mediated cell death pathway during aging. Since the TGF-β, interacts with Pax6 and also gets influenced by Catalase, the Pax6 appears influencing immunological surveillance of brain. The alteration in levels of S100β and genes of oxidative stress management by Pax6 also indicates involvement of Pax6-TGF-β-Catalase axis in aging. The microRNA based regulation is also reflected because the miR335 suppresses the Pax6 expression and acts as anti-oncogenic target in glioma. The implication of Pax6 could also be explored towards possibilities of modifying the rate of aging and reversal of aging clock because the Pax6 interacts with p53 and gets altered during aging.