Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis

Fan, Shou-Zen; Lin, Cheng-Sheng; Wei, Yu-Wen; Yeh, Sung‐Ling; Tsai, Yi-Hsuan; Lee, Andrew Chengyu; Lin, Wei−Sheng; Wang, Pei‐Yu

doi:10.1111/acel.13510

Cited by 37 publications

(27 citation statements)

References 44 publications

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“…However, after QWJR intervention, citric acid decreased and cis-aconitic acid increased, returning to normal. Citric acid is not only the primary source of adenosine triphosphate (ATP) but also an inflammatory signal whose accumulation may help generate pro-inflammatory mediators, such as NO and reactive oxygen species (ROS) ( Infantino et al, 2014 ; Fan et al, 2021 ). In viral pneumonia, the TCA cycle in M1-type macrophages is blocked, leading to citric acid accumulation and succinate.…”

Section: Discussionmentioning

confidence: 99%

Qing-Wen-Jie-Re Mixture Ameliorates Poly (I:C)-Induced Viral Pneumonia Through Regulating the Inflammatory Response and Serum Metabolism

Zhang²,

Wang³

et al. 2022

Front. Pharmacol.

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Qing-Wen-Jie-Re mixture (QWJR) has been used in the treatment of the coronavirus disease 2019 (COVID-19) in China. However, the protective mechanisms of QWJR on viral pneumonia remain unclear. In the present study, we first investigated the therapeutic effects of QWJR on a rat viral pneumonia model established by using polyinosinic-polycytidylic acid (poly (I:C)). The results indicated that QWJR could relieve the destruction of alveolar-capillary barrier in viral pneumonia rats, as represented by the decreased wet/dry weight (W/D) ratio in lung, total cell count and total protein concentration in bronchoalveolar lavage fluid (BALF). Besides, QWJR could also down-regulate the expression of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6. More M1-type macrophage polarization was detected by calculating CD86+ cells and CD206+ cells and validated by the decline of inducible nitric oxide synthase (iNOS) and elevated arginase-1 (Arg-1) in lung. Finally, serum untargeted metabolomics analysis demonstrated that QWJR might take effect through regulating arginine metabolism, arachidonic acid (AA) metabolism, tricarboxylic acid (TCA) cycle, nicotinate and nicotinamide metabolism processes.

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Section: Discussionmentioning

confidence: 99%

Qing-Wen-Jie-Re Mixture Ameliorates Poly (I:C)-Induced Viral Pneumonia Through Regulating the Inflammatory Response and Serum Metabolism

Zhang²,

Wang³

et al. 2022

Front. Pharmacol.

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“…Other nutrient sensors, such as AMP-activated protein kinase (AMPK) and sirtuin signaling, tend to be deregulated with aging. AMPK, a key regulator of cellular energy, is activated in C. elegans during nutrient-deprivationor low-energetic conditions and extends the lifespan [ 26 , 27 ], Drosophila [ 28 ] and mammals [ 29 ] by inhibiting TORC1 activity, activating autophagy, and improving cellular stress resistance. Sirtuins, a class of histone deacetylases involved in lifespan regulation, protect against the aging process by enhancing cellular stress resistance [ 30 ].…”

Section: Deregulated Nutrient Sensingmentioning

confidence: 99%

Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease

Cheng¹,

Li²,

Du³

et al. 2022

Aging and disease

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Aging is a major global challenge, and there is growing demand for new strategies to address the burden of aging. The intensive search for antiaging agents has led to the discovery of a variety of drugs that promote the extension of healthspan and/or life. Metformin is a safe, effective, and globally affordable antihyperglycemic agent that has gained much attention in recent years as a potential antiaging treatment. Metformin has been shown to significantly delay the onset of age-related diseases and increase lifespan in several model organisms. In this paper, we reviewed aging hallmarks and the role of metformin in countering these hallmarks. We examined the beneficial effects of metformin on several age-related diseases and the feasibility of metformin as an agent to extend lifespan and healthspan. Finally, we discussed new research directions to better understand the translational potential of metformin in humans.

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“…However, the long-term effects of exogenous citrate administration on overall health has not been well explored. In a recent study, we demonstrated that dietary citrate supplementation was associated with lifespan extension, decreased hemolymph glucose and triglyceride, and reduced ATP/ADP ratio in fruit flies fed on a relatively highcalorie diet [1]. Furthermore, we found that AMPactivated protein kinase (AMPK) was activated and target of rapamycin (TOR) signaling was suppressed in these flies.…”

mentioning

confidence: 93%

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2022

Aging

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Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri bution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 37 publications

References 44 publications

Qing-Wen-Jie-Re Mixture Ameliorates Poly (I:C)-Induced Viral Pneumonia Through Regulating the Inflammatory Response and Serum Metabolism

Qing-Wen-Jie-Re Mixture Ameliorates Poly (I:C)-Induced Viral Pneumonia Through Regulating the Inflammatory Response and Serum Metabolism

Metformin's Mechanisms in Attenuating Hallmarks of Aging and Age-Related Disease

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