**3.6 The quinic acid material**

566 Selected Topics in DNA Repair

systems (Zhang et al 1993) as well as humans (Fu et al 1989). The depleted cells have an increased sensitivity to DNA damage and the levels of poly (ADP-ribose) production in cultured cells (as cited by Jacobson, E L in Poirier and Moreau (eds) 1992) or in rat liver (Rawling et al 1994) were significantly lower after mild nicotinamide deficiency. On the other hand, when niacin was given as a supplement to ordinary nutrition (i.e. above known dietary levels) the NAD pool increased and the cells were less sensitive to oxygen radicals (Weitberg 1989). Therefore, it is obvious from this review of the prior art that the primary mechanism of action of nicotinamide/niacin differs from carotenoids and zinc in that the cell's potential for energy metabolism is increased by amplifying NAD and ATP pool supplies (i.e. these biochemicals are the energy sources of living organisms) which in turn is useful to cells, tissues and organs to reduce DNA damage, enhance DNA repair (i.e. poly ADP-ribosylation) and stimulate immune function where the relevance to the disease state

The known molecular mechanisms of zinc source are described herein. Zinc differs from the resveratrol, carotenoids and nicotinamide with regard to its mechanism of action in that it influences disease development and immune function by being an essential co-factor in several enzyme functions involving replication, DNA repair and antioxidant defense of cells. Zinc is required for cell replication and DNA polymerase activity (Williams, RO et al 1973). There are two zinc fingers in the DNA binding domain of the poly adenosine diphosphate ribosyl transferase (ADPRT) gene and other DNA repair proteins (Dawat, P. et al 1995; Matsuda, T. et al1 1995; Chiriccolo, M. et al 1993) which contain cysteine residues (i.e. an amino acid), and if these cysteine residues are oxidized at their thiol constituents, they would prevent DNA binding and participation in DNA repair (Mazen et al 1989; de Murcia, G. et al 1989; Pero 1995; Althaus et al 1994). Moreover, superoxide dismutase is an antioxidant enzyme protecting cells from the harmful superoxide anion because this radical is a substrate for the enzymatic reaction that also requires zinc as a cofactor (Brunori and

The known molecular mechanisms of DMAE material is described herein. Dimethylaminoethanol (DMAE) material, also known as deanol, is a naturally occurring substance that has been studied as a possible anti-ageing therapy that can also improve cognitive function, reduce neurological stress, improves immunity and DNA repair especially in skin. It is the precursor to choline and may increase acetylcholine levels (Grossman 2005). While choline is known to be the precursor of acetylcholine, a recognized neurotransmitter, DMAE may also prove to offer a more direct approach to this function by moving into the brain, being acted on by an enzyme (methylation), and thereby undergoing conversion into choline directly where it is needed. DMAE inhibits production of the agerelated pigment lipofuscin, which accumulates in all aging tissues. This is significant because cells with increased lipofuscin cause lysosomes to perform poorly, which leads to increased accumulation of poorly functioning mitochondria and increased reactive oxygen species (ROS) production (Terman and Brunk 2006). Evidence also suggests that DMAE decreases the extent of crosslinking of proteins possibly by acting as a free-radical scavenger

is apparent (Pero et al 1995).

**3.4 The zinc material** 

Rotilio 1984).

**3.5 The DMAE material** 

(Nagy and Nagy 1980).

A water extract of Cat's Claw (Uncaria species) called AC-11 or one of its active ingredients quinic acid are also DNA repair enhancers that do not metabolically compete with resveratrol material, carotenoid material, nicotinamide material, DMAE material or zinc material, and as such could be added to the DNA repair mixture without inducing metabolic competition and thus inhibiting DNA repair instead of being synergistic, because the mode of action of AC-11/quinic acid to increasing DNA repair is novel to inducing DNA repair by increasing uptake of urinary tryptophan and nicotinamide (Pero 2008, Pero et al 2009b, Pero and Lund 2009a , 2011). The quinic acid analog being selected for commericial development is from the group consisting of quinic acid salts, chelates, and Uncaria or other plant extracts containing quinic acid analogs (Pero 2001, 2002, 2005, 2006, 2009a, 2009b; Pero and Garret 2010a).
