Authors: 
Kathryn Annett [1], Alexander Bürkle [2], Muriel Malaisé [2], Orla Duggan [1], Robin Freeburn [1], Paul Hyland [3], Christopher Barnett [3], Anders Wikby [4], Graham Pawelec [5], Yvonne Barnett [1,3]
Category: 
Oral
Conference: 
Abstract: 

Poly(ADP-ribosyl)ation is an immediate response to DNA damage. This post translational modification of nuclear proteins is mostly catalysed by poly(ADP-ribose) polymerase-1 (PARP-1), and has been implicated in several crucial cellular processes including DNA repair, recombination and genomic stability. The aims of this investigation were to assess the age-related maximal cellular capacity for poly(ADP-ribosyl)ation using a novel flow cytometry based assay in human T cell clones and in peripheral blood mononuclear cells (PBMCs) from nonagenarian subjects participating in the Swedish NONA Immune study. A decline in the poly(ADP-ribosyl)ation capacity of CD4+ T cell clones was observed with in vitro ageing. In contrast, SENIEUR donor-derived CD4+ T cell clones did not show any evidence of a decline with increasing age in vitro. PBMCs from NONA subjects were found to have higher levels of poly(ADP-ribose) than controls, although the difference was not statistically significant. The results from this study further support the view that poly(ADP-ribosyl)ation capacity appears to be an important contributor towards longevity.

This work was supported by studentship to KA by the Department of Education and Learning; by a studentship to OD by the University of Ulster; as well as by the following grants by the European Union "Immunology and Ageing in Europe" (ImAginE; contract number QLK6-CT-1999-O2031), "T cell Immunity and Ageing" (T-CIA; contract number QL1C6-CT-2002-02283), and "Nutritional zinc, oxidative stress and immunosenescence: biochemical, genetic and lifestyle implications for healthy ageing" (ZINCAGE; contract number FOOD-CT-2003-506850).

Keywords (Optional): 
ageing
immunosenescence
T cells
poly(ADP-ribosyl)ation
PARP-1