How does the NAD+/NADH ratio affect lifespan in vertebrates?
This study found a statistically significant decline in NAD+:NADH ratios and in intracellular NAD+ with age in the organs of rats. 

They discuss that the activation of  PARP - the  NAD-dependent enzyme Poly(ADP-ribose) polymerase-1 instrumental in DNA repair - increases in aging organs (heart, liver, kidneys). This depletes cellular NAD+ levels via poly(ADP-ribosylation) of proteins. This reduced cellular  NAD+ then reduces the effectiveness of Sirtuins (Sirt1) which can deacetylate tumor-suppressor proteins such as p53.

Here's schematic showing the basic idea from their figure 10:



So, the inference is that oxidative stress in vertebrates increases with age due to lowered cellular NAD+ - i.e.,  consistent with the free-radical theory of aging.  This could mean that lowered cellular NAD+, NAD+/NADH in any given individual may well decrease said individuals lifespan.

The authors of the first study (Braidy et al 2011) suggest that therapies involved in maintaining high NAD+ levels may alleviate age-associated disorders.


Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, et al. (2011) Age Related Changes in NAD+ Metabolism Oxidative Stress and Sirt1 Activity in Wistar Rats. PLoS ONE 6(4)
Smith, J., (2002) Human Sir2 and the 'silencing' of p53 activity, Traneds, Cell Biol. 12, 404