The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae

Abstract

Molecular causes of aging and longevity interventions have witnessed an upsurge in the last decade. The resurgent interests in the application of small molecules as potential geroprotectors and/or pharmacogenomics point to nicotinamide adenine dinucleotide (NAD) and its precursors, nicotinamide riboside, nicotinamide mononucleotide, nicotinamide, and nicotinic acid as potentially intriguing molecules. Upon supplementation, these compounds have shown to ameliorate aging related conditions and possibly prevent death in model organisms. Besides being a molecule essential in all living cells, our understanding of the mechanism of NAD metabolism and its regulation remain incomplete owing to its omnipresent nature. Here we discuss recent advances and techniques in the study of chronological lifespan (CLS) and replicative lifespan (RLS) in the model unicellular organism Saccharomyces cerevisiae . We then follow with the mechanism and biology of NAD precursors and their roles in aging and longevity. Finally, we review potential biotechnological applications through engineering of microbial lifespan, and laid perspective on the promising candidature of alternative redox compounds for extending lifespan.

Low‐Molecular Weight Compounds that Extend the Chronological Lifespan of Yeasts, Saccharomyces cerevisiae, and Schizosaccharomyces pombe

“…[25,120,118,121] In budding yeast, CLS extension by NAM is dependent on Sir2, and NAM extends CLS by suppressing Sir2 activity. [118,117] Phosphoenolpyruvate carboxykinase Pck1 is a key enzyme in the gluconeogenesis pathway, and Sir2 inactivates Pck1 by deacetylation of Lys514. [122] NAM-induced CLS extension does not occur in the absence of Pck1, and NAM may therefore suppress Sir2-induced deacetylation of Pck1 and be involved in activating the gluconeogenesis pathway.…”

“…+ precursor, NAM, promotes RLS extension but has a negative effect on CLS in S. cerevisiae ; Δ sir2 cells have a long CLS. [ 15,118,119 ] Although NAM extends CLS in S. cerevisiae and the lifespan in C. elegans , it does not extend the lifespan in mice. [ 25,120,118,121 ] In budding yeast, CLS extension by NAM is dependent on Sir2, and NAM extends CLS by suppressing Sir2 activity.…”

ecl family genes: Factors linking starvation and lifespan extension in Schizosaccharomyces pombe

“…Prr1 is a transcription factor that promotes the expression of genes involved in oxidative stress response, including ctt1 + , and sexual differentiation, including ste11 + (Calvo et al, 2012;Ohmiya et al, 2000). The induction of genes involved in oxidative stress response requires the formation of a complex with Pap1, another transcription factor involved in this response (Calvo et al, 2012;Yaakoub et al, 2022).…”

“…The induction of genes involved in oxidative stress response requires the formation of a complex with Pap1, another transcription factor involved in this response (Calvo et al, 2012;Yaakoub et al, 2022). Meanwhile, Prr1 also binds upstream of ste11 + at a site at which a heat shock element is present to positively regulate ste11 + expression (Ohmiya et al, 2000). All ecl family genes induce ste11 + in a Prr1-dependent manner Ohtsuka et al, 2012).…”

“…Factors or processes involved in the response to starvation, such as target of rapamycin complex 1 (TORC1) and protein kinase A (PKA), contribute to the control of lifespan from yeast to higher organisms (Folch et al, 2018; Hansen et al, 2018; Kapahi et al, 2017; Kurauchi et al, 2021; Le Couteur et al, 2020). Chronological lifespan (CLS) is defined as the duration of survival of non‐dividing cells, and it represents a model for studying the aging of non‐dividing cells (such as neurons) in higher eukaryotes (Masumura et al, 2019; Odoh et al, 2022; Ohtsuka et al, 2021b). In yeast, the survival rate after entry into the stationary phase is represented by CLS (Kurauchi et al, 2017; Lin & Austriaco, 2014; Matsui et al, 2021; Roux et al, 2010).…”