Hello Dr. Mishra,

regarding question 1:

I think that it is certainly possible that the mitochondrial retrograde response contributes to up-regulation of p21 and down-regulation of cyclin D1. Reduction in mtDNA content, elevated ROS levels and depleted anti-oxidant enzyme activities are all markers that can be related to mitochondrial dysfunction. If this occurs the retrograde response from mitochondria will induce major re-programming of nuclear gene expression patterns. In these works you can find more information:

Butow RA, Avadhani NG (2004) Mitochondrial signaling: the retrograde response. Mol Cell 14: 1–15

Passos J et al. (2007) Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol 5: e110.

Passos J et al. (2007) Mitochondria and ageing: winning and losing in the numbers game. Bioessays 29: 908–917

regarding question 2:

There is a good chance that the effects you observe are mediated by transport of NF kb from the cytoplasm to the nucleus and that this indeed contributes to the establishment of a secretory-associated senescence phenotype. There is an interesting paper describing the relationship between p21 activation and NF kb,

Chang PY, Miyamoto S (2006) Nuclear factor-kappaB dimer exchange promotes a p21(waf1/cip1) superinduction response in human T leukemic cells. Mol Cancer Res 4: 101-12.

I hope this information is useful to you.

Best regards!

Many thanks Dr. Scheckhuber for providing us your insightful views.

Personal regards !