Progressive degeneration of spinal function during ageing is a major cause of frailty and morbidity in the elderly. Understanding why the spine ages and how to reverse it are therefore key to future gains in human health and lifespan. Precursors of NAD+ have attracted attention for their ability to boost mitochondrial function and reverse aspects of aging by activating the sirtuins (SIRT1-7), a family of NAD+-dependent protein deacylases that mimic the beneficial effects of dietary restriction (DR) and exercise. Similarly, hydrogen sulfide (H2S) has recently been shown to extend the lifespan of lower organisms, also by mimicking the effects of DR. The deletion of the SIRT1 gene in mice mimics the loss of capillary density in muscle and exercise capacity that accompanies ageing, while overexpression of SIRT1 has the opposite effect, maintaining endurance levels with progressing age. Treatment of elderly mice with the NAD+ precursor nicotinamide mononucleotide (NMN) with a dose that does not increase mitochondrial activity increases endurance by promoting SIRT1 activity. Co-treatment of elderly mice with NMN and the H2S donor sodium hydrosulfide (NaHS), dramatically improves muscle capillary density and exercise capacity of aged mice via endothelial SIRT1. This finding has major implications for treating the multitude of age-related spine disorders.