The use of a systems approach to increase NAD+ in human participants

npj Aging, Год журнала: 2024, Номер 10(1)

Опубликована: Фев. 1, 2024

Abstract Reversal or mitigation against an age-related decline in NAD + has likely benefits, and this premise driven academic commercial endeavour to develop dietary supplements that achieve outcome. We used a systems-based approach improve on current by targeting multiple points the salvage pathway. In double-blind, randomised, crossover trial, supplement – Nuchido TIME+® (NT) - increased concentration whole blood. This was associated with increase SIRT1 nicotinamide phosphoribosyltransferase (NAMPT) peripheral blood mononucleocytes, lower concentrations of pro-inflammatory cytokines plasma, including reduction interleukin 2 (IL2), glycated serum protein shift glycosylation profile immunoglobulin G (IgG) toward younger biological age, all which are promote healthier ageing trajectory.

Язык: Английский

---

Long-term NMN treatment increases lifespan and healthspan in mice in a sex dependent manner

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 27, 2024

SUMMARY Nicotinamide adenine dinucleotide (NAD) is essential for many enzymatic reactions, including those involved in energy metabolism, DNA repair and the activity of sirtuins, a family defensive deacylases. During aging, levels NAD + can decrease by up to 50% some tissues, repletion which provides range health benefits both mice humans. Whether or not precursor nicotinamide mononucleotide (NMN) extends lifespan mammals known. Here we investigate effect long-term administration NMN on health, cancer burden, frailty male female mice. Without increasing tumor counts severity any tissue, treatment males females increased activity, maintained more youthful gene expression patterns, reduced overall frailty. Reduced with was associated increases Anerotruncus colihominis, gut bacterium lower inflammation longevity slowed accumulation adipose tissue later life improved metabolic but mice, while males, median 8.5%, possible due sex-specific effects metabolism. Together, these data show that chronic delays frailty, alters microbiome, improves mouse lifespan, without burden. These results highlight potential boosters treating age-related conditions importance using sexes interventional studies.

Язык: Английский

---

Metabolite accumulation from oral NMN supplementation drives aging-specific kidney inflammation

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 13, 2024

Abstract The mitochondrial-rich renal tubule cells are key regulators of blood homeostasis via excretion and reabsorption metabolic waste. With age, tubules subject to increasing mitochondrial dysfunction declining nicotinamide adenine dinucleotide (NAD + ) levels, both hampering ATP production efficiency. We tested two interventions in young (6-mo) aged (26-mo) adult male mice: (ELAM), a tetrapeptide clinical trials that improves structure function, mononucleotide (NMN), an NAD intermediate commercially available oral supplement. Kidneys were analyzed from mice after eight weeks treatment with ELAM (3 mg/kg/day), NMN (300 or treated the combined (ELAM+NMN). hypothesized combining pharmacologic treatments ameliorate boost would more effectively reduce kidney aging than either intervention alone. Unexpectedly, kidneys, increased expression genetic markers inflammation (IL-1β Ccl2) injury (Kim-1). Metabolomics endpoint sera showed NMN-treated had higher circulating levels uremic toxins controls mice. ELAM+NMN- accumulated like NMN-only mice, but reduced IL-1β Ccl2 mRNA. This suggests pre-existing underlies susceptibility inflammatory signaling supplementation aged, not young, These findings demonstrate age tissue dependent effects on downstream accumulation highlight need for targeted analysis kidneys assess safety anti-aging supplements older populations. Summary Statement Declining functionally linked popular mechanistic targets therapeutics. Studies have focused riboside (NR) (NAM) cellular , consensus dosage regimen is beneficial tolerable has been reached. show although high sustained liver heart same dosing carries age-associated signs inflammation. Our underscore complex state age- tissue-specific raise questions only about how much, long, at what boosting safe.

Язык: Английский

---

Nicotinamide riboside and nicotinamide mononucleotide facilitate NAD ⁺ synthesis via enterohepatic circulation

Science Advances, Год журнала: 2025, Номер 11(12)

Опубликована: Март 21, 2025

Decreased nicotinamide adenine dinucleotide (oxidized form) (NAD + ) levels are reportedly associated with several aging-related disorders. Thus, supplementation NAD precursors, such as mononucleotide (NMN) and riboside (NR), exhibits beneficial effects against these However, the in vivo metabolic pathways of NMN NR remain to be elucidated. In this study, we comprehensively analyzed fate orally intravenously administered mice using metabolomics. We found that only a small portion was directly absorbed from intestine most them underwent gut microbiota–mediated deamidation conversion nicotinic acid (NA). Moreover, were rapidly degraded into secreted bile followed by NA microbiota. enterohepatic circulated is preferentially used liver. These findings showed indirectly converted via unexpected pathways.

Язык: Английский

---

Nanoformulations-based functionalized boron nitride nanosheets delivering nicotinamide mononucleotide with enhanced in vitro anti-aging properties

Journal of Drug Delivery Science and Technology, Год журнала: 2025, Номер unknown, С. 106846 - 106846

Опубликована: Март 1, 2025

Язык: Английский

---