Poly(ADP-ribosyl)ation capacity of human T lymphocytes in vitro and in vivo as a function of age
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]
1 Cancer and Ageing Research Group, School of Biomedical Sciences, University of Ulster, Coleraine, Northern Ireland BT52 1SA, UK
2 Molecular Toxicology Group, Department of Biology, Box X911, University of Konstanz, D-78457 Konstanz, Germany
3 School of Biomedical and Natural Sciences, College of Science and Technology, Nottingham Trent University, Clifton Campus, Nottingham NG11 8NS, UK
4 Department of Natural Science and Biomedicine, University College of Health Sciences, SE-551, 11 Jönköping, Sweden
5 University of Tübingen, Centre for Medical Research, ZMF, Waldhörnlestr. 22, D-72072 Tübingen, Germany
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).
Key words:
Ageing, immunosenescence, T cells, poly(ADP-ribosyl)ation, PARP-1
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