Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians

Area of Science:

• Biochemistry
• Genetics
• Gerontology

Background:

• Poly(ADP-ribosyl)ation is a crucial DNA damage response pathway involving poly(ADP-ribose) polymerase (PARP).
• Previous studies indicated a correlation between maximal PARP activity and lifespan across mammalian species.

Purpose of the Study:

• To investigate the relationship between poly(ADP-ribosyl)ation capacity and human longevity.
• To compare PARP activity in centenarians and younger control groups.

Main Methods:

• Maximal oligonucleotide-stimulated PARP activity was measured in lymphoblastoid cell lines from 49 centenarians and 51 controls.
• Quantitative western blotting assessed cellular PARP content in a subset of participants.
• A genetic association study analyzed a polymorphic marker in the PARP gene promoter.

Main Results:

• Centenarians exhibited significantly higher maximal PARP activity compared to controls (P=0.031).
• Specific PARP activity, calculated using western blot data, was also significantly higher in centenarians (P=0.006), approximately 1.6-fold.
• Genetic analysis of a PARP promoter polymorphism showed no significant association with longevity or enzyme activity.

Conclusions:

• The findings support the hypothesis that a high poly(ADP-ribosyl)ation capacity is associated with human longevity.
• Specific PARP activity is a robust indicator differentiating centenarians from controls.
• While the studied genetic marker was not associated, the enzymatic activity data strengthens the link between DNA repair and lifespan.