Glycolysis – a key player in the inflammatory response

FEBS Journal, Год журнала: 2020, Номер 287(16), С. 3350 - 3369

Опубликована: Апрель 7, 2020

The inflammatory response involves the activation of several cell types to fight insults caused by a plethora agents, and maintain tissue homoeostasis. On one hand, cells involved in pro‐inflammatory response, such as M1 macrophages, Th1 Th17 lymphocytes or activated microglia, must rapidly provide energy fuel inflammation, which is essentially accomplished glycolysis high lactate production. other regulatory T M2 are immune regulation resolution preferentially use fatty acid oxidation through TCA cycle main source for Here, we discuss impact glycolytic metabolism at different steps response. Finally, review wide variety molecular mechanisms could explain relationship between metabolites phenotype, including signalling events, epigenetic remodelling, post‐transcriptional post‐translational modifications. Inflammatory processes common feature many age‐associated diseases, cardiovascular neurodegenerative disorders. finding that immunometabolism be master regulator inflammation broadens avenue treating inflammation‐related pathologies manipulation vascular metabolism.

Язык: Английский

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Aging and Autophagy in the Heart

Circulation Research, Год журнала: 2016, Номер 118(10), С. 1563 - 1576

Опубликована: Май 12, 2016

The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it important to understand molecular mechanisms through which heart becomes either more or less susceptible stress. Cardiac characterized by presence hypertrophy, fibrosis, and accumulation misfolded proteins dysfunctional mitochondria. Macroautophagy (hereafter referred as autophagy) a lysosome-dependent bulk degradation mechanism that essential for intracellular protein organelle quality control. Autophagy autophagic flux are generally decreased hearts, murine autophagy loss-of-function models develop exacerbated dysfunction accompanied organelles. On contrary, stimulation improves function mouse aggregation removing accumulated proteins, mitochondria, damaged DNA, thereby improving overall cellular environment alleviating aging-associated pathology heart. Increasing lines evidence suggest required many mediate lifespan extension, such caloric restriction, various organisms. These results raise exciting possibility may play an role combating adverse effects In this review, we discuss during aging, how alleviates age-dependent changes heart, level can be restored.

Язык: Английский

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NAD ⁺ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency

Proceedings of the National Academy of Sciences, Год журнала: 2018, Номер 115(8)

Опубликована: Фев. 5, 2018

Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a repair-deficient 3xTgAD/Polβ

Язык: Английский

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The role of lipid metabolism in aging, lifespan regulation, and age‐related disease

Aging Cell, Год журнала: 2019, Номер 18(6)

Опубликована: Сен. 27, 2019

Abstract An emerging body of data suggests that lipid metabolism has an important role to play in the aging process. Indeed, a plethora dietary, pharmacological, genetic, and surgical lipid‐related interventions extend lifespan nematodes, fruit flies, mice, rats. For example, impairment genes involved ceramide sphingolipid synthesis extends both worms flies. The overexpression fatty acid amide hydrolase or lysosomal lipase prolongs life Caenorhabditis elegans , while diacylglycerol enhances longevity C. Drosophila melanogaster . removal adipose tissue rats, increased expression apolipoprotein D survival flies mice. Mouse can be additionally extended by genetic deletion acyltransferase 1, treatment with steroid 17‐α‐estradiol, ketogenic diet. Moreover, phospholipase A2 receptor improves various healthspan parameters progeria mouse model. Genome‐wide association studies have found several variants associated human aging. epsilon 2 4 alleles E are extreme late‐onset neurodegenerative disease, respectively. In humans, blood triglyceride levels tend increase, lysophosphatidylcholine decrease age. Specific phospholipid profiles also been shown change age exceptional longevity. These suggest may improve lipids likely represent rich source biomarkers.

Язык: Английский

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Mitochondria as central regulators of neural stem cell fate and cognitive function

Nature reviews. Neuroscience, Год журнала: 2018, Номер 20(1), С. 34 - 48

Опубликована: Ноя. 21, 2018

Язык: Английский

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