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Drawing of stem cells

Stem cell activity is metabolically demanding, and NAD deficits can mess things up. Indeed, stem cells don't age better than other parts of the system, and NAD replenishment seems to make a difference.


Here are the studies:

Aug 14, 2023

Stem cells - Inflammation - Liver - Digestion - IBD

Cellular & Molecular Immunology

NAD+ salvage governs the immunosuppressive capacity of mesenchymal stem cells

Fang, Jiankai


This study demonstrated that...NAD+ metabolism governs the anti-inflammatory function of mesenchymal stem cells during inflammation.

Aug 10, 2023

Stem Cells


Nicotinamide Riboside Improves Stemness of Human Adipose-Derived Stem Cells and Inhibits Terminal Adipocyte Differentiation

Chinnapaka, Somaiah


NR administration improves the stemness-related genes expression in ASCs and mitigates their propensity for adipocyte differentiation. These results suggest that NR treatment holds promise as a potential strategy to rejuvenate the stemness of aged adipose-derived stem cells.

Jun 17, 2023

Bone - Stem Cells - Reproduction - Pregnancy

Nature Communications

The NAD salvage pathway in mesenchymal cells is indispensable for skeletal development in mice

Warren, Aaron


Our studies demonstrate that administration of NR during pregnancy in mice can prevent severe developmental defects caused by genetic inhibition of NAD production. In view of the multiple clinical syndromes already linked to defective NAD production, our findings raise hope of their attenuation and perhaps prevention.

Oct 19, 2022

Muscle - Stem Cells

Frontiers in Cell Development Biology

Nicotinamide riboside kinases regulate skeletal muscle fiber-type specification and are rate-limiting for metabolic adaptations during regeneration

Sonntag, Tanja


During regeneration, muscle stem cells (MuSCs) from [mice with both NRK1 and NRK2 knocked out] hyper-proliferate but fail to differentiate. Double NRK Knockout also alters the recovery of NAD+ during muscle regeneration as well as mitochondrial adaptations and ECM remodeling required for tissue repair. These metabolic perturbations result in a transient delay of muscle regeneration which normalizes during myofiber maturation at late stages of regeneration via over-compensation of anabolic IGF1-Akt signaling.

Oct 10, 2022

Muscle - Aging - Stem Cells

JCI Insight

A randomized placebo-controlled trial of nicotinamide riboside and pterostilbene supplementation in experimental muscle injury in elderly individuals

Jensen, Jonas


...The objective of this study was to investigate if supplementation with nicotinamide riboside and pterostilbene (NRPT) promotes skeletal muscle regeneration after muscle injury in elderly individuals by improved recruitment of MuSCs...Daily supplementation with 1,000 mg NR and 200 mg PT is safe but does not improve recruitment of the MuSC pool or other measures of muscle recovery in response to injury or subsequent regeneration in elderly individuals.

Apr 28, 2022

Muscle - Gut Microbiota - Stem Cells - Mitochondria - Obesity

Science Advances

Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation and gut microbiota composition in a twin study

Lapatto, Helena


We aimed to determine whether long-term nicotinamide riboside (NR) supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twins from 22 BMI-discordant monozygotic pairs were supplemented with an escalating dose of NR (250-1000 mg/day) for 5 months ( entry NCT03951285). NR improved blood and tissue NAD+ metabolism, muscle mitochondrial number, myoblast differentiation and gut microbiota composition independent of BMI. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD+ metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.

Nov 29, 2021

Reproduction - Pregnancy - Stem Cells - Heart / Vascular

Cell Death & Disease

Nicotinamide promotes cardiomyocyte derivation and survival through kinase inhibition in human pluripotent stem cells

Meng, Ya


This study not only demonstrates nicotinamide as a useful factor for cardiomyocyte production in regenerative medicine, but also implicates that nicotinamide could have a profound impact on embryogenesis if it is prescribed during pregnancy.

Sep 21, 2021

Aging - Brain - Ataxia - Stem Cells - Bone Marrow - Inflammation

Aging Cell

NAD+ augmentation with nicotinamide riboside improves lymphoid potential of Atm−/− and old mice HSCs

Zong, Le


Our data suggest that NR administration in compromised hematopoietic systems (NAD+ depleted system) drives cell-intrinsic changes of the HSC compartment together with an overall reduction in circulating inflammatory cytokines. However, once the aged system has been exposed to NR, the effects of removing the supplementation may have undesirable consequences. Thus, once a deficient system is exposed to NAD+ supplementation, to maintain the benefits we have demonstrated, the regimen may need to be sustained long-term...Our results showed significant alterations in lineage commitment of HSCs after NR treatment, with enhanced lymphoid potential. This correlated with changes in inflammatory cytokines and transcriptional alterations of the HSCs. While transplantation of aged NR-treated HSCs reproduced the enhanced lymphoid output seen in the transcriptional profiles, the changes in potential are not sustained after NR withdrawal in the aged mice, and the rebound phenotype appear to exacerbate aging phenotypes. Our results highlight the importance of the duration of NR exposure and the timing of initial exposure to derive robust, balanced lineage outputs from HSCs.

May 11, 2021

Bone Marrow - Stem Cells - Aging

Nature Communications

Nicotinamide riboside attenuates age-associated metabolic and functional changes in hematopoietic stem cells

Sun, Xuan


With age, hematopoietic stem cells (HSC) undergo changes in function, including reduced regenerative potential and loss of quiescence, which is accompanied by a significant expansion of the stem cell pool that can lead to haematological disorders. Elevated metabolic activity has been implicated in driving the HSC ageing phenotype. Here we show that nicotinamide riboside (NR), a form of vitamin B3, restores youthful metabolic capacity by modifying mitochondrial function in multiple ways including reduced expression of nuclear encoded metabolic pathway genes, damping of mitochondrial stress and a decrease in mitochondrial mass and network-size. Metabolic restoration is dependent on continuous NR supplementation and accompanied by a shift of the aged transcriptome towards the young HSC state, more youthful bone marrow cellular composition and an improved regenerative capacity in a transplant setting. Consequently, NR administration could support healthy ageing by re-establishing a more youthful hematopoietic system.

Mar 27, 2019

Aging - Stem Cells

Aging Cell

NAD+ supplementation rejuvenates aged gut adult stem cells

Igarashi, Masaki


The tissue decline due to aging is associated with the deterioration of adult stem cell function. Here we show the number and proliferative activity of intestinal stem cells (ISCs) but not Paneth cells decline during aging, as does ISC function assessed ex vivo. Levels of SIRT1 and activity of mTORC1 also decline with aging. The treatment with the NAD(+) precursor nicotinamide riboside (NR) rejuvenates ISCs from aged mice and reverses an impaired ability to repair gut damage. The effect of NR is blocked by the mTORC1 inhibitor rapamycin or the SIRT1 inhibitor EX527. These findings demonstrate that small molecules affecting the NAD/SIRT1/mTORC1 axis may guide a translational path for maintenance of the intestine during aging.

Mar 7, 2019

Blood - Stem Cells

Cell Stem Cell

The NAD-Booster Nicotinamide Riboside Potently Stimulates Hematopoiesis through Increased Mitochondrial Clearance

Vannini, Nicola


Our results reveal NR and NMN as potential boosters of hematopoiesis [production of blood cells in the marrow]...Given the efficient enhancement of megakaryopoiesis, NR supplementation could also prove beneficial for the treatment of refractory autoimmune idiopathic thrombocytopenic purpura (ITP) or other auto-immune bone marrow failure syndromes [megakaryopoiesis is the process by which bone marrow progenitor cells develop into mature megakaryocytes (MKs), which in turn produce platelets required for normal hemostasis.]

Jun 17, 2016

Aging - Stem Cells - Muscle - Muscular Dystrophy


NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice

Zhang, Hanbo


Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD+) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD+ precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice. NR also prevented MuSC senescence in the mdx (C57BL/10ScSn-Dmdmdx/J) mouse model of muscular dystrophy. We furthermore demonstrate that NR delays senescence of neural SCs and melanocyte SCs and increases mouse life span. Strategies that conserve cellular NAD+ may reprogram dysfunctional SCs and improve life span in mammals.

NAD Research - Stem Cells

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