NAD metabolism: Role in senescence regulation and aging

Aging Cell, Год журнала: 2023, Номер 23(1)

Опубликована: Июль 9, 2023

Abstract The geroscience hypothesis proposes that addressing the biology of aging could directly prevent onset or mitigate severity multiple chronic diseases. Understanding interplay between key aspects biological hallmarks is essential in delivering promises hypothesis. Notably, nucleotide nicotinamide adenine dinucleotide (NAD) interfaces with several aging, including cellular senescence, and changes NAD metabolism have been shown to be involved process. relationship senescence appears complex. On one hand, accumulation DNA damage mitochondrial dysfunction induced by low + can promote development senescence. other state occurs during may inhibit SASP as this secretory phenotype are both highly metabolically demanding. However, date, impact on progression has not fully characterized. Therefore, explore implications replacement therapies, it consider their interactions We propose a comprehensive understanding boosting strategies senolytic agents necessary advance field.

Язык: Английский

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Roles of chromatin and genome instability in cellular senescence and their relevance to ageing and related diseases

Nature Reviews Molecular Cell Biology, Год журнала: 2024, Номер 25(12), С. 979 - 1000

Опубликована: Окт. 3, 2024

Язык: Английский

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Reductive stress: The key pathway in metabolic disorders induced by overnutrition

Journal of Advanced Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

The balance of redox states is crucial for maintaining physiological homeostasis. For decades, the focus has been mainly on concept oxidative stress, which involved in mechanism almost all diseases. However, robust evidence highlighted that reductive other side spectrum, plays a pivotal role development various diseases, particularly those related to metabolism and cardiovascular health. In this review, we present an extensive array occurrence stress its significant implications metabolic Reductive defined as shift cellular towards more reduced state, characterized by excess endogenous reductants (such NADH, NADPH, GSH) over their oxidized counterparts (NAD+, NADP+, GSSG). While predominant studied obesity, disorders, growing underscores critical stress. This review discusses how contributes pathologies, emphasizing effects key processes. example, excessive NADH accumulation can disrupt mitochondrial function impairing electron transport chain, leading decreased ATP production increased reactive oxygen species. endoplasmic reticulum (ER), equivalents hampers protein folding, triggering ER activating unfolded response, lead insulin resistance compromised Furthermore, explore antioxidant supplementation exacerbate further shifting balance, potentially undermining beneficial exercise, health, aggravating obese individuals. body calls reevaluation disease pathogenesis therapeutic interventions.

Язык: Английский

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Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children

Reproduction, Год журнала: 2024, Номер 167(6)

Опубликована: Март 12, 2024

In light of the increasing age first-time fathers, this article summarizes current scientific knowledge base on reproductive aging in male, including sperm quality and health impacts for offspring. The emerging role NAD decline is highlighted.

Язык: Английский

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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

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A new clinical age of aging research

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер unknown

Опубликована: Сен. 1, 2024

Aging is a major risk factor for variety of diseases, thus, translation aging research into practical applications driven by the unmet need existing clinical therapeutic options. Basic and translational efforts are converging at critical stage, yielding insights how fundamental mechanisms used to identify promising geroprotectors or therapeutics. This review highlights several areas from perspective, including senescent cell targeting, alleviation inflammaging, optimization metabolism with endogenous metabolites precursors. Refining our understanding these key areas, especially angle, may help us better understand attenuate processes improve overall health outcomes.

Язык: Английский

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Immunometabolism: signaling pathways, homeostasis, and therapeutic targets

MedComm, Год журнала: 2024, Номер 5(11)

Опубликована: Ноя. 1, 2024

Abstract Immunometabolism plays a central role in sustaining immune system functionality and preserving physiological homeostasis within the organism. During differentiation activation, cells undergo metabolic reprogramming mediated by complex signaling pathways. Immune maintain are influenced microenvironmental cues. A series of immunometabolic enzymes modulate cell function metabolizing nutrients accumulating products. These reverse cells’ differentiation, disrupt intracellular pathways, regulate responses, thereby influencing disease progression. The huge population enzymes, ubiquity, complexity regulation have kept mechanisms related to many diseases from being discovered, what has been revealed so far is only tip iceberg. This review comprehensively summarized enzymes’ multiple such as T cells, macrophages, natural killer dendritic cells. By classifying dissecting immunometabolism implications diseases, summarizing analyzing advancements research clinical applications inhibitors targeting these this intended provide new perspective concerning for understanding system, offer novel insight into future therapeutic interventions.

Язык: Английский

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Nicotinamide: A Multifaceted Molecule in Skin Health and Beyond

Medicina, Год журнала: 2025, Номер 61(2), С. 254 - 254

Опубликована: Фев. 1, 2025

Nicotinamide (NAM), the amide form of vitamin B3, is a precursor to essential cofactors nicotinamide adenine dinucleotide (NAD⁺) and NADPH. NAD⁺ integral numerous cellular processes, including metabolism regulation, ATP production, mitochondrial respiration, reactive oxygen species (ROS) management, DNA repair, senescence, aging. NAM supplementation has demonstrated efficacy in restoring energy, repairing damage, inhibiting inflammation by suppressing pro-inflammatory cytokines release. Due its natural presence variety foods excellent safety profile—even at high doses up 3 g/day—NAM extensively used chemoprevention non-melanoma skin cancers treatment dermatological conditions such as blistering diseases, atopic dermatitis, rosacea, acne vulgaris. Recently, anti-aging properties have elevated NAM’s prominence skincare formulations. Beyond repair energy replenishment, significantly impacts oxidative stress reduction, cell cycle apoptosis modulation. Despite these multifaceted benefits, comprehensive molecular mechanisms underlying actions remain not fully elucidated. This review consolidates recent research shed light on mechanisms, emphasizing critical role health therapeutic potential. By enhancing our understanding, this work underscores importance continued exploration into applications, aiming inform future clinical practices innovations.

Язык: Английский

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Nicotinamide Mononucleotide and Nicotinamide Riboside Improve Dyslipidemia and Fatty Liver but Promote Atherosclerosis in Apolipoprotein E Knockout Mice

Pharmaceuticals, Год журнала: 2025, Номер 18(3), С. 281 - 281

Опубликована: Фев. 20, 2025

Background: Nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR) are intermediary products in NAD+ metabolism. NMN NR supplementation can elevate levels tissues, addressing health issues associated with aging obesity. However, the impact of on atherosclerosis remains incompletely elucidated. Methods: C57BL/6J Apolipoprotein E knockout (ApoE−/−) mice were used to explore serum lipids, fatty liver, atherosclerosis. Additionally, various suppliers, administration protocols, doses ApoE−/− investigated. Results: The intragastric (300 mg/kg) (230 reduced body weight, liver but aggravated after 4 months different suppliers. Atherosclerosis also deteriorated 2 protocols (intragastric water administration) existing plaques. effects dose-dependent, around 100 mg/kg had little harmful Conclusions: improve dyslipidemia promote mice. These findings emphasize safe dosage for clinical trials NMN.

Язык: Английский

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Nicotinamide adenine dinucleotide rejuvenates septic bone marrow mesenchymal stem cells

World Journal of Stem Cells, Год журнала: 2025, Номер 17(2)

Опубликована: Фев. 24, 2025

Sepsis is a severe illness characterized by systemic and multiorgan reactive responses damage. However, the impact of sepsis on bone marrow, particularly marrow mesenchymal stem cells (BMSCs), less reported. BMSCs are critical stromal in microenvironment that maintain stability hematopoietic homeostasis; however, impairment caused remains unknown. To investigate effects underlying mechanisms. were obtained from healthy donors patients with sepsis. We compared self-renewal capacity, differentiation potential, supportive ability vitro. Senescence septic was assessed using β-galactosidase staining, senescence-associated secretory phenotype, intracellular oxygen species levels, expression P16 P21. Finally, changes after nicotinamide adenine dinucleotide (NAD) treatment evaluated. Septic showed decreased proliferation self-renewal, bias towards adipogenic differentiation, weakened osteogenic differentiation. Additionally, capacity declines The levels aging markers significantly higher BMSCs. After NAD treatment, recovery trend, increased capacities. resulted sirtuin 3 (SIRT3) BMSCs, whereas restored SIRT3 expression, enhanced superoxide dismutase enzyme activity, reduced maintained mitochondrial function, ultimately rejuvenated accelerates as evidenced decline capabilities, well support functions. These deficiencies can be effectively reversed via NAD/SIRT3/superoxide pathway.

Язык: Английский

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