Trends in Endocrinology and Metabolism, Год журнала: 2022, Номер 33(4), С. 266 - 280
Опубликована: Фев. 17, 2022
Язык: Английский
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
Процитировано
700
Nature Reviews Endocrinology, Год журнала: 2022, Номер 18(4), С. 243 - 258
Опубликована: Фев. 10, 2022
Язык: Английский
Процитировано
554
Endocrine Reviews, Год журнала: 2020, Номер 42(1), С. 77 - 96
Опубликована: Сен. 8, 2020
Metformin is a first-line therapy for the treatment of type 2 diabetes, due to its robust glucose-lowering effects, well-established safety profile, and relatively low cost. While metformin has been shown have pleotropic effects on glucose metabolism, there general consensus that major effect in patients with diabetes mostly mediated through inhibition hepatic gluconeogenesis. However, despite decades research, mechanism by which inhibits this process still highly debated. A key reason these discrepant likely inconsistency dosage across studies. Widely studied mechanisms action, such as complex I leading AMPK activation, only observed context supra-pharmacological (>1 mM) concentrations, do not occur clinical setting. Thus, challenged recent years new proposed. Based observation alters cellular redox balance, redox-dependent action described several groups. Recent studies clinically relevant (50-100 μM) concentrations inhibit gluconeogenesis substrate-selective manner both vitro vivo, supporting action. Here, we review current literature regarding metformin's molecular
Язык: Английский
Процитировано
516
Nature Immunology, Год журнала: 2021, Номер 22(6), С. 687 - 698
Опубликована: Май 13, 2021
Язык: Английский
Процитировано
388
Nature Aging, Год журнала: 2021, Номер 1(10), С. 870 - 879
Опубликована: Окт. 7, 2021
Язык: Английский
Процитировано
342
Nature Reviews Endocrinology, Год журнала: 2023, Номер 19(8), С. 460 - 476
Опубликована: Май 2, 2023
Язык: Английский
Процитировано
326
Nature Aging, Год журнала: 2021, Номер 1(9), С. 769 - 782
Опубликована: Сен. 14, 2021
Язык: Английский
Процитировано
283
Biomedicines, Год журнала: 2021, Номер 9(5), С. 524 - 524
Опубликована: Май 7, 2021
Alzheimer's disease (AD) is a neurodegenerative associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise increasing age. There are currently no effective modifying treatments for AD, resulting in increasingly large socioeconomic personal costs. Increasing age an increase low-grade chronic inflammation (inflammaging) that may contribute the process AD. Although exact mechanisms remain unclear, aberrant elevation reactive oxygen nitrogen species (RONS) levels from several endogenous exogenous processes brain not only affect cell signaling, but also trigger cellular senescence, inflammation, pyroptosis. Moreover, compromised immune privilege allows infiltration peripheral cells infectious agents play role. Additionally, meta-inflammation as well gut microbiota dysbiosis drive neuroinflammatory process. Considering inflammatory/immune pathways dysregulated parallel cognitive dysfunction elucidating relationship between central nervous system facilitate development safe therapy We discuss some current ideas on inflammaging appear summarize details few immunomodulatory strategies being developed selectively target detrimental aspects neuroinflammation without affecting defense against pathogens tissue damage.
Язык: Английский
Процитировано
204
Frontiers in Physiology, Год журнала: 2022, Номер 12
Опубликована: Янв. 11, 2022
Astrocytes play key roles in the regulation of brain energy metabolism, which has a major impact on functions, including memory, neuroprotection, resistance to oxidative stress and homeostatic tone. Energy demands are very large, as they continuously account for 20-25% whole body's consumption. supply is tightly linked neuronal activity, providing origin signals detected by widely used functional imaging techniques such magnetic resonance positron emission tomography. In particular, neuroenergetic coupling regulated astrocytes through glutamate uptake that triggers astrocytic aerobic glycolysis leads glucose lactate release, mechanism known Astrocyte Neuron Lactate Shuttle. Other neurotransmitters noradrenaline Vasoactive Intestinal Peptide mobilize glycogen, reserve exclusively localized astrocytes, also resulting release. then transferred neurons where it used, after conversion pyruvate, rapid substrate, signal modulates excitability, homeostasis, expression survival plasticity genes. Importantly, more generally cerebral metabolism progressively deteriorate aging age-associated neurodegenerative diseases Alzheimer's disease. This decreased actually represents common feature several neurological pathologies. Here, we review critical role how dysregulation astrocyte-mediated metabolic pathways involved hypometabolism. Further, summarize recent efforts at preclinical clinical stages target hypometabolism development new therapeutic interventions age-related diseases.
Язык: Английский
Процитировано
172
Cells, Год журнала: 2022, Номер 11(3), С. 359 - 359
Опубликована: Янв. 21, 2022
Acute inflammation is a physiological response to injury or infection, with cascade of steps that ultimately lead the recruitment immune cells clear invading pathogens and heal wounds. However, chronic arising from continued presence initial trigger, dysfunction signalling and/or effector pathways, harmful health. While successful ageing in older adults, including centenarians, associated low levels inflammation, elevated increases risk poor health death. Hence has been described as one seven pillars ageing. Age-associated sterile, chronic, low-grade commonly termed inflammageing-it not simply consequence increasing chronological age, but also marker biological ageing, multimorbidity, mortality risk. inflammageing was initially thought be caused by "continuous antigenic load stress", reports last two decades describe much more complex phenomenon involving cellular senescence system. In this review, we explore some main sources consequences context immunosenescence highlight potential interventions. particular, assess contribution age-associated identify patterns pro- anti-inflammatory markers characteristic inflammageing, alterations system finally ways diet, exercise, pharmacological interventions can reduce thus, improve later life
Язык: Английский
Процитировано
163