Nutrition, longevity and disease: From molecular mechanisms to interventions

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

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Making sense of the ageing methylome

Nature Reviews Genetics, Год журнала: 2022, Номер 23(10), С. 585 - 605

Опубликована: Май 2, 2022

Язык: Английский

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The ups and downs of caloric restriction and fasting: from molecular effects to clinical application

EMBO Molecular Medicine, Год журнала: 2021, Номер 14(1)

Опубликована: Ноя. 15, 2021

Язык: Английский

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Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial

Nature Aging, Год журнала: 2023, Номер unknown

Опубликована: Фев. 9, 2023

The geroscience hypothesis proposes that therapy to slow or reverse molecular changes occur with aging can delay prevent multiple chronic diseases and extend healthy lifespan

Язык: Английский

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Metabolism and Colorectal Cancer

Annual Review of Pathology Mechanisms of Disease, Год журнала: 2022, Номер 18(1), С. 467 - 492

Опубликована: Ноя. 2, 2022

Reprogrammed metabolism is a hallmark of colorectal cancer (CRC). CRC cells are geared toward rapid proliferation, requiring nutrients and the removal cellular waste in nutrient-poor environments. Intestinal stem (ISCs), primary cell origin for CRCs, must adapt their along adenoma-carcinoma sequence to unique features complex microenvironment that include interactions with intestinal epithelial cells, immune stromal commensal microbes, dietary components. Emerging evidence implicates modifiable risk factors related environment, such as diet, important pathogenesis. Here, we focus on describing ISCs, diets influence initiation, genetics metabolism, tumor microenvironment. The mechanistic links between environmental factors, metabolic adaptations, enhancing or supporting tumorigenesis becoming better understood. Thus, greater knowledge holds promise improved prevention treatment.

Язык: Английский

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Mechanisms of spermidine-induced autophagy and geroprotection

Nature Aging, Год журнала: 2022, Номер 2(12), С. 1112 - 1129

Опубликована: Дек. 22, 2022

Язык: Английский

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Spermidine is essential for fasting-mediated autophagy and longevity

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

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A 5:2 intermittent fasting regimen ameliorates NASH and fibrosis and blunts HCC development via hepatic PPARα and PCK1

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

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Chronic intermittent fasting impairs β cell maturation and function in adolescent mice

Cell Reports, Год журнала: 2025, Номер 44(2), С. 115225 - 115225

Опубликована: Янв. 18, 2025

Язык: Английский

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Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation

Cell Metabolism, Год журнала: 2022, Номер 34(6), С. 836 - 856.e5

Опубликована: Май 16, 2022

Язык: Английский

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