Longevity-Promoting Pathways and Transcription Factors Respond to and Control Extracellular Matrix Dynamics During Aging and Disease

Vidović, Tinka; Ewald, Collin Y.

doi:10.3389/fragi.2022.935220

Cited by 11 publications

(8 citation statements)

References 156 publications

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“…One observation is that chronic age-related pathologies heavily remodel the ECM during disease development and progression [280]. Not so surprising is that interventions that slow aging and prevent chronic diseases also rebalance pathological ECM remodeling [280]. Interestingly, analyzing chromatin immunoprecipitation (ChIP) sequencing and transcriptomic data, we found that the 12 most established longevity-promoting transcription factors (i.e., CREB1, FOXO1,3, GATA1,2,3,4, HIF1A, JUN, KLF4, MYC, NFE2L2/Nrf2, RELA/NF-κB, REST, STAT3,5A, and TP53/p53), directly and indirectly transcriptionally regulate ECM genes [280].…”

Section: Longevity Interventions Promoting Ecm Homeostasismentioning

confidence: 99%

Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity

2023

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The biomechanical properties of extracellular matrices (ECM) and their consequences for cellular homeostasis have recently emerged as a driver of aging. Here we review the age-dependent deterioration of ECM in the context of our current understanding of the aging processes. We discuss the reciprocal interactions of longevity interventions with ECM remodeling. And the relevance of ECM dynamics captured by the matrisome and the matreotypes associated with health, disease, and longevity. Furthermore, we highlight that many established longevity compounds promote ECM homeostasis. A large body of evidence for the ECM to qualify as a hallmark of aging is emerging, and the data in invertebrates is promising. However, direct experimental proof that activating ECM homeostasis is sufficient to slow aging in mammals is lacking. We conclude that further research is required and anticipate that a conceptual framework for ECM biomechanics and homeostasis will provide new strategies to promote health during aging.

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Section: Longevity Interventions Promoting Ecm Homeostasismentioning

confidence: 99%

Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity

2023

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“…SIRT1 is a class III histone deacetylase protein and belongs to a family comprising seven members (SIRT1-SIRT7) with different functions and intracellular localization. Sirtuins are key players in several age-related disorders, including cancer, neurodegeneration, and cardiovascular diseases [52]. Specifically, SIRT1, which shows a nuclear localization, was implicated in the modulation of genes responsible for the control of metabolism and was demonstrated to be able to promote insulin sensitivity, counteracting the detrimental impact of chronic inflammation [53].…”

Section: Candidate Mediator Moleculesmentioning

confidence: 99%

Circadian Clock Desynchronization and Insulin Resistance

Catalano

Vito

Cassano

et al. 2022

IJERPH

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The circadian rhythm regulates biological processes that occur within 24 h in living organisms. It plays a fundamental role in maintaining biological functions and responds to several inputs, including food intake, light/dark cycle, sleep/wake cycle, and physical activity. The circadian timing system comprises a central clock located in the suprachiasmatic nucleus (SCN) and tissue-specific clocks in peripheral tissues. Several studies show that the desynchronization of central and peripheral clocks is associated with an increased incidence of insulin resistance (IR) and related diseases. In this review, we discuss the current knowledge of molecular and cellular mechanisms underlying the impact of circadian clock dysregulation on insulin action. We focus our attention on two possible mediators of this interaction: the phosphatases belonging to the pleckstrin homology leucine-rich repeat protein phosphatase family (PHLPP) family and the deacetylase Sirtuin1. We believe that literature data, herein summarized, suggest that a thorough change of life habits, with the return to synchronized food intake, physical activity, and rest, would doubtless halt the vicious cycle linking IR to dysregulated circadian rhythms. However, since such a comprehensive change may be incompatible with the demand of modern society, clarifying the pathways involved may, nonetheless, contribute to the identification of therapeutic targets that may be exploited to cure or prevent IR-related diseases.

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Section: Introductionmentioning

confidence: 99%

“…This is of interest, since ECM modulation has important implications in tumor invasion and metastasis. Interestingly, ECM homeostasis seems to be linked to the aging process and anti-aging interventions as well (15). Besides, in the nematode Caenorhabditis elegans (C. elegans) , HIF-1 activation through loss of the nematode orthologue of pVHL (VHL-1) has been shown to induce longevity(16,17).…”

Section: Introductionmentioning

confidence: 99%

“…ECM related genes have been shown to be regulated not only by pVHL/VHL-1 (18)several other well-established longevity-related transcription factors ( e.g. FOXO3, Nrf2, TP53 ) (15). Furthermore, established longevity inducing compounds such Rapamycin, Metformin, and Aspirin do also change ECM composition in a number of model organisms (19) Most importantly, ECM modulation has been linked directly and causally to lifespan-extension in C. elegans (20).…”

Section: Introductionmentioning

confidence: 99%

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A VHL-1;HIF-1/SQRD1/COL-88 axis links extracellular matrix formation with longevity inCaenorhabditis elegans

Salgueiro,

Esmaillie,

Bohl

et al. 2024

Preprint

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The extracellular matrix (ECM) is a pivotal three-dimensional network crucial for tissue organization, cellular communication, and fundamental cellular processes, where collagens are the major chemical entity in amount. ECM deregulation is directly involved with several pathologies, such as tumour growth and invasiveness, atherosclerosis, and diabetic nephropathy. Mutations in the von Hippel-Lindau tumour suppressor (pVHL) cause VHL syndrome, a multi-tumour syndrome commonly associated with clear cell renal carcinoma (ccRCC). Loss of pVHL is associated with the activation of hypoxia-inducible factor (HIF) signaling. Mutation of VHL-1 in the nematode Canorhabditis elegans has been shown to increase lifespan and stress resistance. Interestingly, considering recent findings on the involvement of collagens in the regulation of lifespan, we also observed these animals to show defects in body morphology in a HIF-1 dependent manner. Based on this finding, we established a link between HIF-1 activation upon loss of VHL-1 and ECM defects associated with alterations in collagen expression. An RNAi screen examining genes upregulated in vhl-1 mutant worms revealed the sulfide quinone oxidoreductase sqrd-1 to mediate the change in body morphology. SQRD-1 is essential to the HIF-1 dependent increase in several collagen genes. One of these genes, col-88, partly mediates both the impact of loss of VHL-1 on lifespan extension and body length. The downregulation of the uncharacterised col-88 partially restores lifespan extension and reduces body size of vhl-1/sqrd-1 to vhl-1(ok161) single mutant. This study contributes to the increasing body of evidence linking lifespan extension and the ECM and now implicates this axis in hypoxia-signaling. These findings are of special interest considering the role of ECM integrity in tumour growth and metastasis.

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Longevity-Promoting Pathways and Transcription Factors Respond to and Control Extracellular Matrix Dynamics During Aging and Disease

Cited by 11 publications

References 156 publications

Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity

Extracellular Matrix Dynamics as an Emerging yet Understudied Hallmark of Aging and Longevity

Circadian Clock Desynchronization and Insulin Resistance

A VHL-1;HIF-1/SQRD1/COL-88 axis links extracellular matrix formation with longevity inCaenorhabditis elegans

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