AGE

, 37:62

Analysis of gene expression during aging of CGNs in culture: implication of SLIT2 and NPY in senescence

  • K. Preeti Gupta
  • Pankaj Singh Dholaniya
  • Anil Chekuri
  • Anand K. Kondapi
Article

DOI: 10.1007/s11357-015-9789-6

Cite this article as:
Gupta, K.P., Dholaniya, P.S., Chekuri, A. et al. AGE (2015) 37: 62. doi:10.1007/s11357-015-9789-6

Abstract

Senescence is the major key factor that leads to the loss of neurons throughout aging. Cellular senescence is not the consequence of single cause, but there are multiple aspects which may induce senescence in a cell. Various causes such as gene expression, molecular interactions and protein processing and chromatin organization are described as causal factor for senescence. It is well known that the damage to the nuclear or mitochondrial DNA contributes to the aging either directly by inducing the apoptosis/cellular senescence or indirectly by altering cellular functions. The significant nuclear DNA damage with the age is directly associated with the continuous declining in DNA repair. The continuous decline in expression of topoisomerase 2 beta (Topo IIβ) in cultured cerebellar granule neurons over time indicated the decline in the repair of damage DNA. DNA Topo IIβ is an enzyme that is crucial for solving topological problems of DNA and thus has an important role in DNA repair. The enzyme is predominantly present in non-proliferating cells such as neurons. In this paper, we have studied the genes which were differentially expressed over time in cultured cerebellar granule neurons (CGNs) and identified potential genes associated with the senescence. Our results showed that the two genes neuropeptide Y (Npy) and Slit homolog 2 (Drosophila) (Slit2) gradually increase during aging, and upon suppression of these two genes, there was gradual increase in cell viability along with restoration of the expression of Topo IIβ and potential repair proteins.

Graphical abstract

Keywords

Senescence Oxidative stress Ageing ROS Cerebellar granule neurons 

Abbreviations

CGNs

Cerebellar granule neurons

DSBs

Double strand breaks

ROS

Reactive oxygen species

SSBs

Single-strand breaks

Topo IIβ

Topoisomerase IIβ

Copyright information

© American Aging Association 2015

Authors and Affiliations

  • K. Preeti Gupta
    • 1
  • Pankaj Singh Dholaniya
    • 1
  • Anil Chekuri
    • 1
  • Anand K. Kondapi
    • 1
  1. 1.Department of Biotechnology and Bioinformatics, School of Life SciencesUniversity of HyderabadHyderabadIndia