NAD+ and Sirtuins in Aging and Disease

By S. Imai, L. Guarente. Trends in Cell Biology, 2014

1,326 citations recorded by the source corpus.

Nicotinamide adenine dinucleotide (NAD+) is a classical coenzyme mediating many redox reactions. NAD+ also plays an important role in the regulation of NAD+-consuming enzymes, including sirtuins, poly-ADP-ribose polymerases (PARPs), and CD38/157 ectoenzymes. NAD+ biosynthesis, particularly mediated by nicotinamide phosphoribosyltransferase (NAMPT), and SIRT1 function together to regulate metabolism and circadian rhythm. NAD+ levels decline during the aging process and may be an Achilles’ heel, causing defects in nuclear and mitochondrial functions and resulting in many age-associated pathologies. Restoring NAD+ by supplementing NAD+ intermediates can dramatically ameliorate these age-associated functional defects, counteracting many diseases of aging, including neurodegenerative diseases. Thus, the combination of sirtuin activation and NAD+ intermediate supplementation may be an effective anti-aging intervention, providing hope to aging societies worldwide.

Subfields: Epidemiology, Geriatrics and Gerontology, Physiology

View Paper: https://www.semanticscholar.org/paper/bb66d302ceabf3c2e70c045e6803c77ddfcea723

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. Jun Yoshino
2. S. Imai

In Geriatrics and Gerontology

1. Jun Yoshino
2. S. Imai
3. K. Mills
4. Y. Sasaki
5. Alessia Grozio
6. Lei Shi
7. B. Tu
8. L. Guarente

In Physiology

1. Jun Yoshino
2. S. Imai
3. Lei Shi
4. B. Tu

Citations in the corpus

• Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice (2016, positive): “Whereas these compounds were originally developed as pharmaceutical drugs, some endogenous compounds might also have the potential to achieve healthy and productive lives even at a very old age (Imai, 2010; Imai and Guarente, 2014).”
• CD38 dictates age-related NAD decline and mitochondrial dysfunction through a SIRT3-dependent mechanism (2016, positive): “Furthermore, PARP1 has been proposed to be involved in NAD decline in tissues, and SIRT1 is an NAD-dependent deacetylase that plays a key role in age-related metabolic phenotypes (Bai et al., 2011; Bai and Cantó, 2012; Imai and Guarente, 2014).”
• Acetyl-CoA and the Regulation of Metabolism: Mechanisms and Consequences (2015, background): “The dependency of sirtuins on NAD+ have led to the hypothesis that their activity could be regulated by fluctuations in NAD+ concentrations [63,64].”
• Therapeutic potential of NAD-boosting molecules: the in vivo evidence (2018, neutral): “In rodents, NR is more efficient in boosting NAD+ than NA and NAM (Trammell et al., 2016a), possibly due to increased uptake (Imai, 2009; Imai and Guarente, 2014; Ratajczak et al., 2016; Revollo et al., 2007a).”
• NAD+ intermediates: The biology and therapeutic potential of NMN and NR (2017, neutral): “In addition, accumulating evidence suggests that NAD+ levels decline with age at a systemic level in diverse organisms, including rodents and humans, contributing to the development of many age-associated pathophysiologies (Canto et al., 2015; Imai and Guarente, 2014; Verdin, 2015).”
• β-Hydroxybutyrate (2017, neutral): “Consumption of NAD+ by PARP or overproduction of NADH may promote age-related diseases by decreasing the activity of sirtuins (53).”