Nicotinamide supplementation phenocopies SIR2 inactivation by modulating carbon metabolism and respiration during yeast chronological aging.
Nicotinamide (NAM), a form of vitamin B3, is a byproduct and noncompetitive inhibitor of the deacetylation reaction catalyzed by Sirtuins. These represent a family of evolutionarily conserved NAD+-dependent deacetylases that are well-known critical regulators of metabolism and aging and whose founding member is Sir2 of Saccharomyces cerevisiae. Here, we investigated the effects of NAM supplementation in the context of yeast chronological aging, the established model for studying aging of postmitotic quiescent mammalian cells. Our data show that NAM supplementation at the diauxic shift results in a phenocopy of chronologically aging sir2Δ cells. In fact, NAM-supplemented cells display the same chronological lifespan extension both in expired medium and extreme Calorie Restriction. Furthermore, NAM allows the cells to push their metabolism toward the same outcomes of sir2Δ cells by elevating the level of the acetylated Pck1. Both these cells have the same metabolic changes that concern not only anabolic pathways such as an increased gluconeogenesis but also respiratory activity in terms both of respiratory rate and state of respiration. In particular, they have a higher respiratory reserve capacity and a lower non-phosphorylating respiration that in concert with a low burden of superoxide anions can affect positively chronological aging.
SYSBIO Centre for Systems Biology Milano, Italy; Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Ivan
I
Orlandi
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Damiano
D
Pellegrino Coppola
SYSBIO Centre for Systems Biology Milano, Italy; Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Maurizio
M
Strippoli
Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Rossella
R
Ronzulli
SYSBIO Centre for Systems Biology Milano, Italy; Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy. Electronic address: marina.vai@unimib.it.
Marina
M
Vai
D002244:Carbon / Q000378:metabolism*; D017353:Gene Deletion; D009536:Niacinamide / Q000378:metabolism* / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism*
D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D009536:Niacinamide; D002244:Carbon; C087778:SIR2 protein, S cerevisiae; D056565:Sirtuin 2
Chronological aging; NAM; Respiration; Sir2