NAD+





Boosting NAD+ improves muscle disease

Abstract

NAD+ is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD+ depletion occurs in patients with degenerative disorders and whether NAD+ repletion improves their symptoms has remained open.

Here, we report systemic NAD+ deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD+-booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively.

Blood NAD+ increased in all subjects, up to 8-fold, and muscle NAD+ of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%.

Our evidence indicates that blood analysis is useful in identifying NAD+ deficiency and points niacin to be an efficient NAD+ booster for treating mitochondrial myopathy.

SOURCE: Cell Metabolism

EDITOR’S NOTE: Increased blood levels of NAD+ were achieved here with a readily available supplement, niacin (vitamin B3).



An acetylation switch of the NLRP3 inflammasome

Abstract

It is well documented that the rate of aging can be slowed, but it remains unclear to which extent aging-associated conditions can be reversed. How the interface of immunity and metabolism impinges upon the diabetes pandemic is largely unknown.

Here, we show that NLRP3, a pattern recognition receptor, is modified by acetylation in macrophages and is deacetylated by SIRT2, an NAD +-dependent deacetylase and a metabolic sensor.

We have developed a cell-based system that models aging-associated inflammation, a defined co-culture system that simulates the effects of inflammatory milieu on insulin resistance in metabolic tissues during aging, and aging mouse models; and demonstrate that SIRT2 and NLRP3 deacetylation prevent, and can be targeted to reverse, aging-associated inflammation and insulin resistance.

These results establish the dysregulation of the acetylation switch of the NLRP3 inflammasome as an origin of aging-associated chronic inflammation and highlight the reversibility of aging-associated chronic inflammation and insulin resistance.

FULL TEXT: Cell Metabolism

EDITOR’S NOTE: the deacetylation step, performed by SIRT2, is switched ‘on’ in healthy cells. This is one more part of the NAD+ / sirtuin puzzle. The goal is to keep NAD+ and sirtuins functioning normally.


NMN and aging

The Sheekey Science Show

NAD+ levels decline as we age. There is some evidence from studies in model organisms that restoring NAD+ levels can increase lifespan/healthspan. One way to restore NAD+ levels is through NMN supplements, which is a precursor to NAD+. In this video, I will go into more detail regarding this and also look at why it could be beneficial and when are the potentially best times for NMN to be taken.

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Niacin: an old lipid drug in a new NAD + dress

Abstract

Niacin, the first antidyslipidemic drug, has been at the center stage of lipid research for many decades before the discovery of statins. However, to date, despite its remarkable effects on lipid profiles, the clinical outcomes of niacin treatment on cardiac events is still debated.

In addition to its historically well-defined interactions with central players of lipid metabolism, niacin can be processed by eukaryotic cells to synthesize a crucial cofactor, NAD+. NAD+ acts as a cofactor in key cellular processes, including oxidative phosphorylation, glycolysis, and DNA repair.

More recently, evidence has emerged that NAD+ also is an essential cosubstrate for the sirtuin family of protein deacylases and thereby has an impact on a wide range of cellular processes, most notably mitochondrial homeostasis, energy homeostasis, and lipid metabolism. NAD+ achieves these remarkable effects through sirtuin-mediated deacetylation of key transcriptional regulators, such as peroxisome proliferator-activated receptor gamma coactivator 1-α, LXR, and SREBPs, that control these cellular processes.

Here, we present an alternative point of view to explain niacin’s mechanism of action, with a strong focus on the importance of how this old drug acts as a control switch of NAD+/sirtuin-mediated control of metabolism.

FULL TEXT: Journal of Lipid Research