NAD metabolism: Role in senescence regulation and aging

Aging Cell, Journal Year: 2023, Volume and Issue: 23(1)

Published: July 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.

Language: Английский

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The therapeutic perspective of NAD+ precursors in age-related diseases

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 702, P. 149590 - 149590

Published: Feb. 2, 2024

Nicotinamide adenine dinucleotide (NAD

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Regulation of and challenges in targeting NAD+ metabolism

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: 25(10), P. 822 - 840

Published: July 18, 2024

Language: Английский

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Anti-aging effects of medicinal plants and their rapid screening using the nematode Caenorhabditis elegans

Phytomedicine, Journal Year: 2024, Volume and Issue: 129, P. 155665 - 155665

Published: April 28, 2024

Aging is the primary risk factor of most chronic diseases in humans, including cardiovascular diseases, osteoporosis and neurodegenerative these extensively damage quality life for elderly individuals. a multifaceted process with numerous factors influencing it. Efficient model organisms are essential research development anti-aging agents, particularly while investigating pharmacological mechanisms. This review discusses application Caenorhabditis elegans studying aging its related signaling pathways, presents an overview studies exploring mechanism screening agents C. elegans. Additionally, summarizes clinical trials to inspire new medications. Literature was searched, analyzed, collected using PubMed, Web Science, Science Direct. The search terms used were "anti-aging", "medicinal plants", "synthetic compounds", "C. elegans", "signal pathway", etc. Several combinations keywords used. Studies conducted or humans included. Articles excluded, if they on silico vitro could not offer effective data. Four compounds mainly derived through synthesis (metformin, rapamycin, nicotinamide mononucleotide, alpha-ketoglutarate) four active ingredients chiefly obtained from plants (resveratrol, quercetin, Astragalus polysaccharide, ginsenosides) introduced emphatically. These exhibit potential effects preclinical studies. investigation their mechanisms can benefit use Medicinal provide valuable resource treating diseases. A wide source raw materials particular plant medicinal having meet diverse pharmaceutical requirements, such as immunomodulatory, anti-inflammation alleviating oxidative stress. possesses advantages scientific short cycle, small size, easy maintenance, genetic tractability conserved biological processes aging. be efficient rapid evaluation slow down

Language: Английский

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Nicotinamide mononucleotide induces autophagy and ferroptosis via AMPK/mTOR pathway in hepatocellular carcinoma

Molecular Carcinogenesis, Journal Year: 2024, Volume and Issue: 63(4), P. 577 - 588

Published: Jan. 10, 2024

Abstract Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Herein, we investigated the role of nicotinamide mononucleotide (NMN) in HCC progression. cells were treated with NMN (125, 250, and 500 μM), then adenine dinucleotide (NAD + ) NADH levels measured to calculate NAD /NADH ratio. Cell proliferation, apoptosis, autophagy ferroptosis determined. AMPK was knocked down confirm involvement AMPK/mTOR signaling. Furthermore, tumor‐inhibitory effect xenograft models. Exposure dose‐dependently increased level ratio cells. After treatment, cell proliferation inhibited, whereas apoptosis enhanced both lines. Additionally, autophagy/ferroptosis activated pathway knockdown partially rescued effects vitro. treatment restrained tumor growth nude mice, autophagy/ferroptosis, promoted necrosis tissues. The results indicate that inhibits progression by inducing via may serve as promising agent for treatment.

Language: Английский

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Ovarian Aging: The Silent Catalyst of Age-Related Disorders in Female Body

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

Age-related diseases have emerged as a global concern the population ages. Consequently, understanding underlying causes of aging and exploring potential anti-aging interventions is imperative. In females, ovaries serve principal organs responsible for ovulation production female hormones. The are related to infertility, menopause, associated menopausal syndromes, with menopause representing culmination ovarian aging. Current evidence indicates that may contribute dysfunction across multiple organ systems, including, but not limited to, cognitive impairment, osteoporosis, cardiovascular disease. Nevertheless, due widespread distribution sex hormone receptors throughout body, affects only these specific also influences broader spectrum age-related in women. Despite this, impact on overall has been largely neglected. This review provides thorough summary diseases, encompassing nervous, circulatory, locomotor, urinary, digestive, respiratory, endocrine systems. Additionally, we outlined prospective therapeutic approaches addressing both aim mitigating their impacts preserving women's fertility, physical health, psychological well-being.

Language: Английский

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Safety and efficacy of long-term nicotinamide mononucleotide supplementation on metabolism, sleep, and nicotinamide adenine dinucleotide biosynthesis in healthy, middle-aged Japanese men

Endocrine Journal, Journal Year: 2024, Volume and Issue: 71(2), P. 153 - 169

Published: Jan. 1, 2024

Obesity and aging are major risk factors for several life-threatening diseases. Accumulating evidence from both rodents humans suggests that the levels of nicotinamide adenine dinucleotide (NAD+), a regulator many biological processes, declines in multiple organs tissues with obesity. Administration an NAD+ intermediate, mononucleotide (NMN), replenishes intracellular mitigates aging- obesity-associated derangements animal models. In this human clinical study, we aimed to investigate safety effects 8-week oral administration NMN on biochemical, metabolic, ophthalmologic, sleep quality parameters as well chronological alterations content peripheral tissues. An 8-week, single-center, single-arm, open-label trial was conducted. Eleven healthy, middle-aged Japanese men received two 125-mg capsules once daily before breakfast. The supplementation regimen well-tolerated; blood mononuclear cells increased over course administration. participants insulin oversecretion after glucose loading, modestly attenuated postprandial hyperinsulinemia, factor coronary artery disease (n = 3). conclusion, overall safely effectively boosted biosynthesis men, showing its potential alleviating hyperinsulinemia.

Language: Английский

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Advancements in NMN biotherapy and research updates in the field of digestive system diseases

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 30, 2024

Nicotinamide mononucleotide (NMN), a crucial intermediate in NAD + synthesis, can rapidly transform into within the body after ingestion. NMN plays pivotal role several important biological processes, including energy metabolism, cellular aging, circadian rhythm regulation, DNA repair, chromatin remodeling, immunity, and inflammation. has emerged as key focus of research fields biomedicine, health care, food science. Recent years have witnessed extensive preclinical studies on NMN, offering valuable insights pathogenesis age- aging-related diseases. Given sustained global interest substantial market expectations for future, here, we comprehensively review milestones biotherapy over past 10 years. Additionally, highlight current field digestive system diseases, identifying existing problems challenges research. The overarching aim this is to provide references further exploration spectrum

Language: Английский

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Dietary Supplementation With NAD+-Boosting Compounds in Humans: Current Knowledge and Future Directions

The Journals of Gerontology Series A, Journal Year: 2023, Volume and Issue: 78(12), P. 2435 - 2448

Published: April 17, 2023

Abstract Advancing age and many disease states are associated with declines in nicotinamide adenine dinucleotide (NAD+) levels. Preclinical studies suggest that boosting NAD+ abundance precursor compounds, such as riboside or mononucleotide, has profound effects on physiological function models of aging disease. Translation these compounds for oral supplementation humans been increasingly studied within the last 10 years; however, clinical evidence raising concentrations can improve is unclear. The goal this review was to synthesize published literature chronic precursors healthy age-related diseases. We identified riboside, co-administered pterostilbene, mononucleotide most common candidates investigations NAD+-boosting improving humans. Studies have performed generally midlife older adults, adults cardiometabolic risk factors overweight obesity, numerous patient populations. Supplementation safe, tolerable, increase related metabolites multiple tissues. Dosing regimens study durations vary greatly across interventions, small sample sizes limit data interpretation outcomes. Limitations future research directions suggested further our understanding potential efficacy extending human health span.

Language: Английский

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Roles of NAD⁺in Health and Aging

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2023, Volume and Issue: 14(1), P. a041193 - a041193

Published: Oct. 17, 2023

Sofie Lautrup1,6, Yujun Hou2,6, Evandro F. Fang1,3 and Vilhelm A. Bohr4,5 1Department of Clinical Molecular Biology, University Oslo Akershus Hospital, 1478 Lørenskog, Norway 2Institute for Regenerative Medicine, Shanghai East Frontier Science Center Stem Cell Research, Key Laboratory Signaling Disease School Life Sciences Technology, Tongji University, 200092, China 3The Norwegian Centre on Healthy Ageing (NO-Age), Oslo, 4DNA Repair Section, National Institute Aging, Institutes Health, Baltimore, Maryland 21224, USA 5Danish Copenhagen, 2200 Denmark Correspondence: e.f.fang{at}medisin.no; vbohr{at}sund.ku.dk

Language: Английский

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