Characterisation of signalling pathways during caloric restriction and in p16 negative hTERT overexpressing fibroblasts.

Project Leader(s): Gabriele Saretzki
Staff: Lin Hsiao-Shih (Msc student), Satomi Miwa (post-doc, CISBAN)
Sponsors: BBSRC targeted studentship (2008-2011)

Caloric restriction (CR) is a model system that has been shown to extend the lifespan in many different organisms. However, the underlying mechanisms and signalling pathways are still greatly elusive.

We generated hTERT (the catalytic subunit of telomerase)-overexpressing fibroblasts that show an improved mitochondrial function. Rare events lead to changes in p16 expression and AKT expression. Since p16 is an important molecule involved in the maintenance of the senescence pathway in vitro and in vivo we will characterise changes between p16 positive and negative hTERT-overexpressing cell lines. Using siRNA we will specifically knock out p16 in normal and hTERT-overexpressing cells and characterise the changes in AKT signalling. In addition we will characterise stress resistance, oxidative stress and respiration in these cells.

In parallel we will apply similar analysis to selected tissues from calorically restricted and aged mice.
We also analyse mitochondrial telomerase in different tissues from CR and ad libitum “free-feeding” mice.

For more information contact:

Gabriele Saretzki


Dr Gabriele Saretzki