AP‐1 is a regulatory transcription factor of inflammaging in the murine kidney and liver

Aging Cell, Год журнала: 2023, Номер 22(7)

Опубликована: Май 8, 2023

Aging is characterized by chronic low-grade inflammation in multiple tissues, also termed "inflammaging", which represents a significant risk factor for many aging-related diseases. However, the mechanisms and regulatory networks underlying inflammaging across different tissues have not yet been fully elucidated. Here, we profiled transcriptomes epigenomes of kidney liver from young aged mice found that activation inflammatory response conserved signature both tissues. Moreover, revealed links between transcriptome changes chromatin dynamics through integrative analysis identified AP-1 ETS family transcription factors (TFs) as potential regulators inflammaging. Further situ validation showed c-JUN (a member family) was mainly activated renal hepatic cells, while increased SPI1 mostly induced elevated infiltration macrophages, indicating these TFs Functional data demonstrated genetic knockdown Fos, major family, significantly attenuated kidneys livers. Taken together, our results signatures liver, providing novel targets development anti-aging interventions.

Язык: Английский

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Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice

Journal of Biomedical Science, Год журнала: 2024, Номер 31(1)

Опубликована: Янв. 23, 2024

Abstract Background CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, persistently high level of promotes longevity and ameliorates an age-related skin phenotype transgenic mice. Here we translate the genetic evidence into pharmaceutical application using potent activator, hesperetin, which enhances expression HEK001 human keratinocytes from older person. We also treated naturally aged mice order to study activator’s anti-aging efficacy. Methods studied biological effects hesperetin on aging using, firstly, cell-based platform, namely keratinocyte cell line established Secondly, used mouse model, old at 21-month old. In latter case, investigate efficacy ultraviolet B (UVB)-induced photoaging skin. identify underlying mechanisms potential pathways involved this process carried out transcriptomic analysis. Finally, knockdown Cisd2 knockout were Cisd2-dependent Results Four findings are pinpointed. Firstly , skin, mainly expressed proliferating epidermal basal layer and, furthermore, sun-exposed epidermis. Secondly person, mitochondrial function protects against reactive oxygen species-induced oxidative stress via increased expression; enhancement CISD2-dependent. Additionally, alleviates UVB-induced damage suppresses matrix metalloproteinase-1 expression, being major indicator keratinocytes. Thirdly analysis revealed that modulates panel differentially genes associated with function, redox homeostasis, inflammation attenuate senescence. Intriguingly, activates two known longevity-associated regulators, FOXO3a FOXM1, suppress senescence-associated secretory phenotype. Finally ameliorate occurs mechanism involving CISD2. Most strikingly, late-life treatment started lasting for 5 months, able retard rejuvenate Conclusions Our results reveal pharmacological elevation stage feasible approach effectively mitigating both intrinsic extrinsic could act as functional food or skincare product fighting

Язык: Английский

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Cellular Metabolism: A Fundamental Component of Degeneration in the Nervous System

Biomolecules, Год журнала: 2023, Номер 13(5), С. 816 - 816

Опубликована: Май 11, 2023

It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning knowledge that disease intimately tied to neurodegenerative disorders, affecting both central and peripheral nervous systems well leading dementia, seventh cause of death. New innovative therapeutic strategies address metabolism, apoptosis, autophagy, pyroptosis, mechanistic target rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), risk factors apolipoprotein E (APOE-ε4) gene coronavirus 2019 (COVID-19) can offer valuable insights for clinical care treatment disorders impacted by disease. Critical insight into modulation these complex pathways are required since mTOR pathways, AMPK activation, improve memory retention in Alzheimer's (AD) DM, promote healthy aging, facilitate clearance β-amyloid (Aß) tau brain, control inflammation, but also may lead cognitive loss long-COVID syndrome through mechanisms include oxidative stress, mitochondrial cytokine release, APOE-ε4 if autophagy other programmed cell death left unchecked.

Язык: Английский

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The impact of aging and oxidative stress in metabolic and nervous system disorders: programmed cell death and molecular signal transduction crosstalk

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 8, 2023

Life expectancy is increasing throughout the world and coincides with a rise in non-communicable diseases (NCDs), especially for metabolic disease that includes diabetes mellitus (DM) neurodegenerative disorders. The debilitating effects of disorders influence entire body significantly affect nervous system impacting greater than one billion people disability peripheral as well cognitive loss, now seventh leading cause death worldwide. Metabolic disorders, such DM, neurologic remain significant challenge treatment care individuals since present therapies may limit symptoms but do not halt overall progression. These clinical challenges to address interplay between warrant innovative strategies can focus upon underlying mechanisms aging-related oxidative stress, cell senescence, death. Programmed pathways involve autophagy, apoptosis, ferroptosis, pyroptosis play critical role oversee processes include insulin resistance, β-cell function, mitochondrial integrity, reactive oxygen species release, inflammatory activation. silent mating type information regulation 2 homolog 1

Язык: Английский

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The Metabolic Basis for Nervous System Dysfunction in Alzheimer’s Disease, Parkinson’s Disease, and Huntington’s Disease

Current Neurovascular Research, Год журнала: 2023, Номер 20(3), С. 314 - 333

Опубликована: Июль 25, 2023

Disorders of metabolism affect multiple systems throughout the body but may have greatest impact on both central and peripheral nervous systems. Currently available treatments behavior changes for disorders that include diabetes mellitus (DM) system diseases are limited cannot reverse disease burden. Greater access to healthcare a longer lifespan led an increased prevalence metabolic neurodegenerative disorders. In light these challenges, innovative studies into underlying pathways offer new treatment perspectives Alzheimer's Disease, Parkinson's Huntington's Disease. Metabolic intimately tied can lead debilitating outcomes, such as multi-nervous disease, susceptibility viral pathogens, long-term cognitive disability. Novel strategies robustly address involve careful consideration cellular metabolism, programmed cell death pathways, mechanistic target rapamycin (mTOR) its associated mTOR Complex 1 (mTORC1), 2 (mTORC2), AMP-activated protein kinase (AMPK), growth factor signaling, risk factors apolipoprotein E (APOE-ε4) gene. Yet, complex necessitate comprehensive understanding achieve clinical outcomes susceptibility, onset, progression.

Язык: Английский

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Peripheral Blood DNA Methylation Changes in Response to Centella asiatica Treatment in Aged Mice

Biology, Год журнала: 2025, Номер 14(1), С. 52 - 52

Опубликована: Янв. 10, 2025

Alterations in epigenetic modifications, like DNA methylation, peripheral blood could serve as a useful, minimally invasive biomarker of the effects anti-aging interventions. This study explores this potential with water extract botanical Centella asiatica (CAW). Eighteen-month-old mice were treated CAW their drinking for 5 weeks alongside vehicle-treated eighteen-month-old C57BL6 mice. Reduced representation bisulfite sequencing (RRBS) was used to identify genome-wide differential methylation CAW-treated aged compared Our results showed distinct enrichment differentially methylated regions (DMRs) nearby genes involved biological processes relevant aging (i.e., antioxidant response, metabolic regulation, cellular metabolism). A difference observed between males and females both number sites state methylation. Moreover, or overlapping DMRs found be enriched related previously described mouse brain calcium circadian rhythm). Together, our data suggest that signature readily accessible, CAW's aging.

Язык: Английский

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Transcriptomes of human primary skin fibroblasts of healthy individuals reveal age‐associated mRNAs and long noncoding RNAs

Aging Cell, Год журнала: 2023, Номер 22(11)

Опубликована: Июль 18, 2023

Abstract Changes in the transcriptomes of human tissues with advancing age are poorly cataloged. Here, we sought to identify coding and long noncoding RNAs present cultured primary skin fibroblasts collected from 82 healthy individuals across a wide spectrum (22–89 years old) who participated GESTALT (Genetic Epigenetic Signatures Translational Aging Laboratory Testing) study National Institute on Aging, NIH. Using high‐throughput RNA sequencing linear regression model, identified 1437 (mRNAs) 1177 circular (lncRNAs) that were differentially abundant as function age. Gene set enrichment analysis (GSEA) revealed select transcription factors implicated coordinating subsets mRNAs, while (LncSEA) RNA‐binding proteins predicted participate age‐associated lncRNA profiles. In summary, report changes global transcriptome, noncoding, propose these transcripts may serve biomarkers therapeutic targets aging skin.

Язык: Английский

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Cornerstone Cellular Pathways for Metabolic Disorders and Diabetes Mellitus: Non-Coding RNAs, Wnt Signaling, and AMPK

Cells, Год журнала: 2023, Номер 12(22), С. 2595 - 2595

Опубликована: Ноя. 9, 2023

Metabolic disorders and diabetes (DM) impact more than five hundred million individuals throughout the world are insidious in onset, chronic nature, yield significant disability death. Current therapies that address nutritional status, weight management, pharmacological options may delay but cannot alter disease course or functional organ loss, such as dementia degeneration of systemic bodily functions. Underlying these challenges onset aging associated with increased lifespan, telomere dysfunction, oxidative stress generation lead to multi-system dysfunction. These hurdles point urgent need underlying mechanisms innovative applications. New treatment strategies involve non-coding RNA pathways microRNAs (miRNAs) circular ribonucleic acids (circRNAs), Wnt signaling, Wnt1 inducible signaling pathway protein 1 (WISP1) dependent upon programmed cell death pathways, cellular metabolic AMP-activated kinase (AMPK) nicotinamide, growth factor Non-coding RNAs, AMPK cornerstone for overseeing complex offer avenues DM will necessitate continued appreciation ability each independently unison influence clinical outcome.

Язык: Английский

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Induction of Somatic Embryogenesis in Plants: Different Players and Focus on WUSCHEL and WUS-RELATED HOMEOBOX (WOX) Transcription Factors

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(24), С. 15950 - 15950

Опубликована: Дек. 15, 2022

In plants, other cells can express totipotency in addition to the zygote, thus resulting embryo differentiation; this appears evident apomictic and epiphyllous plants. According Haberlandt's theory, all plant regenerate a complete if nucleus membrane system are intact. fact, under vitro conditions, ectopic embryos adventitious shoots develop from many organs of mature body. We beginning understand how determination processes regulated cell specialization occurs. However, we still need unravel mechanisms whereby interprets its position, decides fate, communicates it others. The induction somatic embryogenesis might be based on growth regulator signal (auxin) determine an appropriate cellular environment factors, including stress expression or meristem identity transcription factors (TFs). Still, far having view regulatory genes, their target action hierarchy. As animals, epigenetic reprogramming also plays essential role re-establishing competence differentiated undergo embryogenesis. Herein, describe functions WUSCHEL-RELATED HOMEOBOX (WOX) regulating differentiation-dedifferentiation process developmental phase regenerated structures.

Язык: Английский

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Programmed versus non-programmed evolution of aging. What is the evidence?

Experimental Gerontology, Год журнала: 2023, Номер 175, С. 112162 - 112162

Опубликована: Апрель 5, 2023

The evolutionary meaning and basic molecular mechanisms involved in the determination of longevity remain an unresolved problem. Currently, different theories are on offer response to these biological traits explain enormous range longevities observed animal kingdom. These may be grouped into those that defend non-programmed aging (non-PA) propose existence programmed (PA). In present article we examine many observational experimental data from both field laboratory sound reasoning accumulated recent decades compatible not with PA non-PA aging. analyses briefly summarized discussed. Our conclusion is most favour a possible contribution antagonist pleiotropy various cases.

Язык: Английский

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