Long-term consumption of green tea EGCG enhances murine health span by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis, and immunosenescence

Sharma, Rohit; Kumar, Ravi; Sharma, Anamika; Goel, Abhishek; Padwad, Yogendra

doi:10.1016/j.jnutbio.2022.109068

Cited by 28 publications

(16 citation statements)

References 65 publications

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“…There is also evidence that the rate of development of SC is not linear with age and is also tissue-dependent suggesting variable predisposition to biological aging depending upon the tissue type (Karin et al, 2019 ). We have also recently reported that adipose tissue is more vulnerable to the development of age-associated senescence-like features which were predominant from the age of 14 months in experimental mice (Sharma et al, 2022 ). A startling common link between SC and various age-related diseases is also rapidly gaining attention.…”

Section: Cellular Senescence In Aging: Molecular Mechanisms and Syste...mentioning

confidence: 75%

“…In fact, quercetin was the first non-synthetic molecule identified with a senolytic activity (Zhu et al, 2015 ) and since then the combination of dasatinib and quercetin has shown promising results in alleviating SC burden in both preclinical and clinical studies resulting in improved organ functions and lifespan (Hickson et al, 2019 ; Novais et al, 2021 ). Our lab has previously identified that tea polyphenol EGCG can also act as a senolytic and can extend murine lifespan by decreasing SC burden in multiple tissues (Kumar et al, 2019 ; Sharma et al, 2022 ). Similarly, other polyphenols such as fisetin (Zhu et al, 2017 ) and piperlongumine (Wang et al, 2016 ) as well as polyphenols-rich fractions of Silybum marianum flower (Woo et al, 2021 ) have also been reported as senolytic agents.…”

Section: Secondary Diet Constituents and Cellular Senescencementioning

confidence: 99%

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Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review

Diwan

Sharma

2022

Food Sci Biotechnol

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The process of cellular senescence is rapidly emerging as a modulator of organismal aging and disease. Targeting the development and removal of senescent cells is considered a viable approach to achieving improved organismal healthspan and lifespan. Nutrition and health are intimately linked and an appropriate dietary regimen can greatly impact organismal response to stress and diseases including during aging. With a renewed focus on cellular senescence, emerging studies demonstrate that both primary and secondary nutritional elements such as carbohydrates, proteins, fatty acids, vitamins, minerals, polyphenols, and probiotics can influence multiple aspects of cellular senescence. The present review describes the recent molecular aspects of cellular senescence-mediated understanding of aging and then studies available evidence of the cellular senescence modulatory attributes of major and minor dietary elements. Underlying pathways and future research directions are deliberated to promote a nutrition-centric approach for targeting cellular senescence and thus improving human health and longevity.

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Section: Cellular Senescence In Aging: Molecular Mechanisms and Syste...mentioning

confidence: 75%

Section: Secondary Diet Constituents and Cellular Senescencementioning

confidence: 99%

Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review

Diwan

Sharma

2022

Food Sci Biotechnol

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“…In yeast, iron limitation increases lifespan by inhibiting TORC1 and inducing autophagy [ 83 ]. Epigallocatechin gallate, an iron chelator, extends mice and rats’ lifespans by increasing the activation of autophagy and decreasing oxidative stress [ 90 , 91 ]. As TORC1 activity was lower in ncr1 ∆ cells ( Figure 4 B), the increase in the autophagic flux of the mutant treated with BPS is, probably, TORC1 independent.…”

Section: Resultsmentioning

confidence: 99%

Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann–Pick Type C1

Martins

Costa

Vilaça

et al. 2023

IJMS

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Niemann–Pick type C1 (NPC1) is an endolysosomal transmembrane protein involved in the export of cholesterol and sphingolipids to other cellular compartments such as the endoplasmic reticulum and plasma membrane. NPC1 loss of function is the major cause of NPC disease, a rare lysosomal storage disorder characterized by an abnormal accumulation of lipids in the late endosomal/lysosomal network, mitochondrial dysfunction, and impaired autophagy. NPC phenotypes are conserved in yeast lacking Ncr1, an orthologue of human NPC1, leading to premature aging. Herein, we performed a phosphoproteomic analysis to investigate the effect of Ncr1 loss on cellular functions mediated by the yeast lysosome-like vacuoles. Our results revealed changes in vacuolar membrane proteins that are associated mostly with vesicle biology (fusion, transport, organization), autophagy, and ion homeostasis, including iron, manganese, and calcium. Consistently, the cytoplasm to vacuole targeting (Cvt) pathway was increased in ncr1∆ cells and autophagy was compromised despite TORC1 inhibition. Moreover, ncr1∆ cells exhibited iron overload mediated by the low-iron sensing transcription factor Aft1. Iron deprivation restored the autophagic flux of ncr1∆ cells and increased its chronological lifespan and oxidative stress resistance. These results implicate iron overload on autophagy impairment, oxidative stress sensitivity, and cell death in the yeast model of NPC1.

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“…Cell senescence activation-induced SASPs which were manifested by pro-inflammatory cytokine release to neighboring tissue. Chronic SASP-associated inflammation may have then promoted inflammatory environments in the gut, which possibly enhanced gut permeability, immune activation, and gut microbiome composition [ 54 , 55 ]. Additionally, gut microbiota pathogens can upregulate gut and systemic inflammatory reactions, increase intestinal permeability, and contribute to AD-associated neuropathology and cognitive decline [ 11 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease

Tun

Wang

Gao

et al. 2023

IJMS

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Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory loss and personality changes that ultimately lead to dementia. Currently, 50 million people worldwide suffer from dementia related to AD, and the pathogenesis underlying AD pathology and cognitive decline is unknown. While AD is primarily a neurological disease of the brain, individuals with AD often experience intestinal disorders, and gut abnormalities have been implicated as a major risk factor in the development of AD and relevant dementia. However, the mechanisms that mediate gut injury and contribute to the vicious cycle between gut abnormalities and brain injury in AD remain unknown. In the present study, a bioinformatics analysis was performed on the proteomics data of variously aged AD mouse colon tissues. We found that levels of integrin β3 and β-galactosidase (β-gal), two markers of cellular senescence, increased with age in the colonic tissue of mice with AD. The advanced artificial intelligence (AI)-based prediction of AD risk also demonstrated the association between integrin β3 and β-gal and AD phenotypes. Moreover, we showed that elevated integrin β3 levels were accompanied by senescence phenotypes and immune cell accumulation in AD mouse colonic tissue. Further, integrin β3 genetic downregulation abolished upregulated senescence markers and inflammatory responses in colonic epithelial cells in conditions associated with AD. We provide a new understanding of the molecular actions underpinning inflammatory responses during AD and suggest integrin β3 may function as novel target mediating gut abnormalities in this disease.

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Long-term consumption of green tea EGCG enhances murine health span by mitigating multiple aspects of cellular senescence in mitotic and post-mitotic tissues, gut dysbiosis, and immunosenescence

Cited by 28 publications

References 65 publications

Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review

Nutritional components as mitigators of cellular senescence in organismal aging: a comprehensive review

Iron Limitation Restores Autophagy and Increases Lifespan in the Yeast Model of Niemann–Pick Type C1

Integrin β3-Mediated Cell Senescence Associates with Gut Inflammation and Intestinal Degeneration in Models of Alzheimer’s Disease

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