Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances DOI Creative Commons
Qiu Jiang, Jie Liu, Shan Huang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 10, 2025

Abstract In the context of global ageing, prevalence neurodegenerative diseases and dementia, such as Alzheimer’s disease (AD), is increasing. However, current symptomatic disease-modifying therapies have achieved limited benefits for in clinical settings. Halting progress neurodegeneration cognitive decline or even improving impaired cognition function are clinically meaningful goals treatments diseases. Ageing primary risk factor their associated comorbidities, vascular pathologies, elderly individuals. Thus, we aim to elucidate role ageing from perspective a complex system, which brain core peripheral organs tissues form holistic network support functions. During progressive deterioration structure entire body hampers its active adaptive responses various stimuli, thereby rendering individuals more vulnerable Consequently, propose that prevention treatment should be grounded antiageing rejuvenation means complemented by interventions targeting disease-specific pathogenic events. This integrated approach promising strategy effectively prevent, pause slow down progression

Язык: Английский

Hallmarks of aging: An expanding universe DOI Creative Commons
Carlos López‐Otín, Marı́a A. Blasco, Linda Partridge

и другие.

Cell, Год журнала: 2023, Номер 186(2), С. 243 - 278

Опубликована: Янв. 1, 2023

Язык: Английский

Процитировано

2975
Circadian alignment of early onset caloric restriction promotes longevity in male C57BL/6J mice DOI
Victoria A. Acosta-Rodríguez, Filipa Rijo‐Ferreira,

Mariko Izumo

и другие.

Science, Год журнала: 2022, Номер 376(6598), С. 1192 - 1202

Опубликована: Май 5, 2022

Caloric restriction (CR) prolongs life span, yet the mechanisms by which it does so remain poorly understood. Under CR, mice self-impose chronic cycles of 2-hour feeding and 22-hour fasting, raising question if is calories, or time day that cause this increased span. We show here 30% CR was sufficient to extend span 10%; however, a daily fasting interval circadian alignment acted together 35% in male C57BL/6J mice. These effects were independent body weight. Aging induced widespread increases gene expression associated with inflammation decreases genes encoding components metabolic pathways liver from ad libitum-fed at night ameliorated these aging-related changes. Our results interventions promote longevity provide perspective further explore aging.

Язык: Английский

Процитировано

260
Nutrition, longevity and disease: From molecular mechanisms to interventions DOI Creative Commons
Valter D. Longo, Rozalyn M. Anderson

Cell, Год журнала: 2022, Номер 185(9), С. 1455 - 1470

Опубликована: Апрель 1, 2022

Diet as a whole, encompassing food composition, calorie intake, and the length frequency of fasting periods, affects time span in which health functional capacity are maintained. Here, we analyze aging nutrition studies simple organisms, rodents, monkeys, humans to link longevity conserved growth metabolic pathways outline their role age-related disease. We focus on feasible nutritional strategies shown delay and/or prevent diseases through epidemiological, model organism, clinical, centenarian underline need avoid malnourishment frailty. These findings integrated define diet based multi-pillar approach adjusted for age status optimize lifespan healthspan humans.

Язык: Английский

Процитировано

230
Dietary regulation in health and disease DOI Creative Commons
Qi Wu,

Zhijie Gao,

Xin Yu

и другие.

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

Опубликована: Июль 23, 2022

Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan delaying ageing various species such as yeast, drosophila, rodent, primate human. It emerges develop precision-nutrition therapeutics slow age-related biological processes treat diverse diseases. However, nutritive advantages frequently diversify among individuals well organs tissues, which brings challenges this field. In review, we summarize different forms of dietary interventions extensively prescribed improvement disease treatment pre-clinical or clinical. We discuss nutrient-mediated mechanisms including metabolic regulators, metabolism pathways, epigenetic circadian clocks. Comparably, describe diet-responsive effectors by influence endocrinic, immunological, microbial neural states responsible improving health preventing multiple diseases humans. Furthermore, expatiate patterns dietotheroapies, fasting, calorie-restricted diet, ketogenic high-fibre plants-based protein restriction diet with specific reduction amino acids microelements, potentially affecting morbid states. Altogether, emphasize profound nutritional therapy, highlight crosstalk explored critical factors individualized therapeutic approaches predictors.

Язык: Английский

Процитировано

104
Defining the age-dependent and tissue-specific circadian transcriptome in male mice DOI Creative Commons
Christopher A. Wolff, Miguel A. Gutierrez‐Monreal, Lingsong Meng

и другие.

Cell Reports, Год журнала: 2023, Номер 42(1), С. 111982 - 111982

Опубликована: Янв. 1, 2023

Cellular circadian clocks direct a daily transcriptional program that supports homeostasis and resilience. Emerging evidence has demonstrated age-associated changes in functions. To define age-dependent at the systems level, we profile transcriptome hypothalamus, lung, heart, kidney, skeletal muscle, adrenal gland three age groups. We find tissue-specific clock output changes. Aging reduces number of rhythmically expressed genes (REGs), indicative weakened control. REGs are enriched for hallmarks aging, adding another dimension to our understanding aging. Analyzing differential gene expression within tissue four different times day identifies distinct clusters differentially (DEGs). Increased variability across is common feature aged tissues. This analysis extends landscape aging highlights impact on function temporal expression.

Язык: Английский

Процитировано

95
Cellular rejuvenation: molecular mechanisms and potential therapeutic interventions for diseases DOI Creative Commons

Shuaifei Ji,

Mingchen Xiong,

Huating Chen

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Март 14, 2023

Abstract The ageing process is a systemic decline from cellular dysfunction to organ degeneration, with more predisposition deteriorated disorders. Rejuvenation refers giving aged cells or organisms youthful characteristics through various techniques, such as reprogramming and epigenetic regulation. great leaps in rejuvenation prove that not one-way street, many rejuvenative interventions have emerged delay even reverse the process. Defining mechanism by which roadblocks signaling inputs influence complex programs essential for understanding developing strategies. Here, we discuss intrinsic extrinsic factors counteract cell rejuvenation, targeted core mechanisms involved this Then, critically summarize latest advances state-of-art strategies of rejuvenation. Various methods also provide insights treating specific ageing-related diseases, including reprogramming, removal senescence (SCs) suppression senescence-associated secretory phenotype (SASP), metabolic manipulation, stem cells-associated therapy, dietary restriction, immune heterochronic transplantation, etc. potential applications therapy extend cancer treatment. Finally, analyze detail therapeutic opportunities challenges technology. Deciphering will further into anti-ageing disease treatment clinical settings.

Язык: Английский

Процитировано

85
Diurnal transcriptome landscape of a multi-tissue response to time-restricted feeding in mammals DOI Creative Commons
Shaunak Deota, Terry Lin, Amandine Chaix

и другие.

Cell Metabolism, Год журнала: 2023, Номер 35(1), С. 150 - 165.e4

Опубликована: Янв. 1, 2023

Time-restricted feeding (TRF) is an emerging behavioral nutrition intervention that involves a daily cycle of and fasting. In both animals humans, TRF has pleiotropic health benefits arise from multiple organ systems, yet the molecular basis TRF-mediated not well understood. Here, we subjected mice to isocaloric ad libitum (ALF) or western diet examined gene expression changes in samples taken 22 organs brain regions collected every 2 h over 24-h period. We discovered profoundly impacts expression. Nearly 80% all genes show differential rhythmicity under at least one tissue. Functional annotation these revealed tissue- pathway-specific TRF. These findings resources provide critical foundation for future mechanistic studies will help guide human time-restricted eating (TRE) interventions treat various disease conditions with without pharmacotherapies.

Язык: Английский

Процитировано

72
When a calorie is not just a calorie: Diet quality and timing as mediators of metabolism and healthy aging DOI Creative Commons
Maria M. Mihaylova, Amandine Chaix, Mirela Delibegović

и другие.

Cell Metabolism, Год журнала: 2023, Номер 35(7), С. 1114 - 1131

Опубликована: Июнь 30, 2023

Язык: Английский

Процитировано

50
Spermidine is essential for fasting-mediated autophagy and longevity DOI Creative Commons
Sebastian J. Hofer, Ioanna Daskalaki, Martina Bergmann

и другие.

Nature Cell Biology, Год журнала: 2024, Номер 26(9), С. 1571 - 1584

Опубликована: Авг. 8, 2024

Abstract Caloric restriction and intermittent fasting prolong the lifespan healthspan of model organisms improve human health. The natural polyamine spermidine has been similarly linked to autophagy enhancement, geroprotection reduced incidence cardiovascular neurodegenerative diseases across species borders. Here, we asked whether cellular physiological consequences caloric depend on metabolism. We report that levels increased upon distinct regimens or in yeast, flies, mice volunteers. Genetic pharmacological blockade endogenous synthesis fasting-induced nematodes cells. Furthermore, perturbing pathway vivo abrogated lifespan- healthspan-extending effects, as well cardioprotective anti-arthritic fasting. Mechanistically, mediated these effects via induction hypusination translation regulator eIF5A. In summary, polyamine–hypusination axis emerges a phylogenetically conserved metabolic control hub for fasting-mediated enhancement longevity.

Язык: Английский

Процитировано

43
A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1 DOI Creative Commons
Suchira Gallage, Adnan Ali, Jose Efren Barragan Avila

и другие.

Cell Metabolism, Год журнала: 2024, Номер 36(6), С. 1371 - 1393.e7

Опубликована: Май 7, 2024

The role and molecular mechanisms of intermittent fasting (IF) in non-alcoholic steatohepatitis (NASH) its transition to hepatocellular carcinoma (HCC) are unknown. Here, we identified that an IF 5:2 regimen prevents NASH development as well ameliorates established fibrosis without affecting total calorie intake. Furthermore, the blunted NASH-HCC when applied therapeutically. timing, length, number cycles type diet were critical parameters determining benefits fasting. Combined proteome, transcriptome, metabolome analyses peroxisome-proliferator-activated receptor alpha (PPARα) glucocorticoid-signaling-induced PCK1 act co-operatively hepatic executors response. In line with this, PPARα targets reduced human NASH. Notably, only initiated during active phase mice robustly induced glucocorticoid signaling free-fatty-acid-induced signaling. However, hepatocyte-specific deletion partially abrogated contrast, combined knockdown Ppara Pck1 vivo abolished beneficial outcomes against inflammation fibrosis. Moreover, overexpression alone or together lowered triglycerides steatosis. Our data support notion is a promising intervention subsequent liver cancer.

Язык: Английский

Процитировано

40