From discoveries in ageing research to therapeutics for healthy ageing

Nature, Год журнала: 2019, Номер 571(7764), С. 183 - 192

Опубликована: Июль 10, 2019

Язык: Английский

---

Mechanisms of Cellular Senescence: Cell Cycle Arrest and Senescence Associated Secretory Phenotype

Frontiers in Cell and Developmental Biology, Год журнала: 2021, Номер 9

Опубликована: Март 29, 2021

Cellular senescence is a stable cell cycle arrest that can be triggered in normal cells response to various intrinsic and extrinsic stimuli, as well developmental signals. Senescence considered highly dynamic, multi-step process, during which the properties of senescent continuously evolve diversify context dependent manner. It associated with multiple cellular molecular changes distinct phenotypic alterations, including proliferation unresponsive mitogenic stimuli. Senescent remain viable, have alterations metabolic activity undergo dramatic gene expression develop complex senescence-associated secretory phenotype. compromise tissue repair regeneration, thereby contributing toward aging. Removal attenuate age-related dysfunction extend health span. also act potent anti-tumor mechanism, by preventing potentially cancerous cells. program acts double-edged sword, both beneficial detrimental effects on organism, an example evolutionary antagonistic pleiotropy. Activation p53/p21 WAF1/CIP1 p16 INK4A /pRB tumor suppressor pathways play central role regulating senescence. Several other recently been implicated mediating Herein we review mechanisms underlie growth particular focus why stop dividing, stability arrest, hypersecretory phenotype how different are all integrated.

Язык: Английский

---

NAD+ metabolism and its roles in cellular processes during ageing

Nature Reviews Molecular Cell Biology, Год журнала: 2020, Номер 22(2), С. 119 - 141

Опубликована: Дек. 22, 2020

Язык: Английский

---

NAD+ Intermediates: The Biology and Therapeutic Potential of NMN and NR

Cell Metabolism, Год журнала: 2017, Номер 27(3), С. 513 - 528

Опубликована: Дек. 14, 2017

Язык: Английский

---

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Signal Transduction and Targeted Therapy, Год журнала: 2022, Номер 7(1)

Опубликована: Дек. 16, 2022

Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue cell functions significant increases the risks of various aging-related diseases, including neurodegenerative cardiovascular metabolic musculoskeletal immune system diseases. Although development modern medicine has promoted human health greatly extended life expectancy, aging society, variety chronic diseases have gradually become most important causes disability death elderly individuals. Current research on focuses elucidating how endogenous exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss proteostasis, compromise autophagy, mitochondrial cellular senescence, stem exhaustion, altered intercellular communication, deregulated nutrient sensing) participate regulation aging. Furthermore, thorough pathogenesis to identify interventions that promote longevity caloric restriction, microbiota transplantation, nutritional intervention) clinical treatment methods for (depletion senescent cells, therapy, antioxidative anti-inflammatory treatments, hormone replacement therapy) could decrease incidence turn healthy longevity.

Язык: Английский

---

Mitophagy and Alzheimer’s Disease: Cellular and Molecular Mechanisms

Trends in Neurosciences, Год журнала: 2017, Номер 40(3), С. 151 - 166

Опубликована: Фев. 9, 2017

Язык: Английский

---

Metabolic Control of Longevity

Cell, Год журнала: 2016, Номер 166(4), С. 802 - 821

Опубликована: Авг. 1, 2016

Язык: Английский

---

β-Hydroxybutyrate: A Signaling Metabolite

Annual Review of Nutrition, Год журнала: 2017, Номер 37(1), С. 51 - 76

Опубликована: Авг. 21, 2017

Various mechanisms in the mammalian body provide resilience against food deprivation and dietary stress. The ketone β-hydroxybutyrate (BHB) is synthesized liver from fatty acids represents an essential carrier of energy to peripheral tissues when supply glucose too low for body's energetic needs, such as during periods prolonged exercise, starvation, or absence carbohydrates. In addition its activity metabolite, BHB increasingly understood have cellular signaling functions. These functions broadly link outside environment epigenetic gene regulation function, their actions may be relevant a variety human diseases well aging.

Язык: Английский

---

Nicotinamide riboside is uniquely and orally bioavailable in mice and humans

Nature Communications, Год журнала: 2016, Номер 7(1)

Опубликована: Окт. 10, 2016

Abstract Nicotinamide riboside (NR) is in wide use as an NAD + precursor vitamin. Here we determine the time and dose-dependent effects of NR on blood metabolism humans. We report that human can rise much 2.7-fold with a single oral dose pilot study one individual, elevates mouse hepatic distinct superior pharmacokinetics to those nicotinic acid nicotinamide. further show doses 100, 300 1,000 mg produce increases metabolome first clinical trial also adenine dinucleotide (NAAD), which was not thought be en route for conversion , formed from discover NAAD highly sensitive biomarker effective repletion.

Язык: Английский

---

Potential roles of gut microbiome and metabolites in modulating ALS in mice

Nature, Год журнала: 2019, Номер 572(7770), С. 474 - 480

Опубликована: Июль 22, 2019

Язык: Английский

---