文献精选

Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics

Yuki Saito1† and Takako S. Chikenji 1,2 * †1

Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan, 2 Department of Health Sciences, School of Medicine, Hokkaido University, Sapporo, Japan

Skeletal muscle undergoes vigorous tissue remodeling after injury. However, aging, chronic inflammatory diseases, sarcopenia, and neuromuscular disorders cause muscle loss and degeneration, resulting in muscular dysfunction. Cellular senescence, a state of irreversible cell cycle arrest, acts during normal embryonic development and remodeling after tissue damage; when these processes are complete, the senescent cells are eliminated. However, the accumulation of senescent cells is a hallmark of aging tissues or pathological contexts and may lead to progressive tissue degeneration. The mechanisms responsible for the effects of senescent cells have not been fully elucidated. Here, we review current knowledge about the beneficial and detrimental effects of senescent cells in tissue repair, regeneration, aging, and age-related disease, especially in skeletal muscle. We also discuss how senescence of muscle stem cells and muscle-resident fibro-adipogenic progenitors affects muscle pathologies or regeneration, and consider the possibility that immunosenescence leads to muscle pathogenesis. Finally, we explore senotherapy, the therapeutic targeting of senescence to treat agerelated disease, from the standpoint of improving muscle regeneration.

Keywords: senescence, skeletal muscle, chronic inflammation, aging, muscle regeneration, muscle stem cells, FAPs, fibrosis

Edited by:

Barbara St. Pierre Schneider, University of Nevada, Las Vegas, United States

Reviewed by: Keitaro Yamanouchi, The University of Tokyo, Japan Antoneta Granic, Newcastle University, United Kingdom

*Correspondence: Takako S. Chikenji 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。†

ORCID: Yuki Saito orcid.org/0000-0002-7949-1628 Takako S. Chikenji orcid.org/0000-0003-2832-3656

Specialty section: This article was submitted to Inflammation Pharmacology, a section of the journal Frontiers in Pharmacology

Received: 11 July 2021

Accepted: 23 August 2021

Published: 06 September 2021

Citation: Saito Y and Chikenji TS (2021) Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics. Front. Pharmacol. 12:739510.

doi: 10.3389/fphar.2021.739510

Cellular senescence and wound healing in aged and diabetic skin

Arisa Kita1,2 , Sena Yamamoto3 , Yuki Saito1 * and Takako S. Chikenji 3 *

1 Department of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan, 2 Department of Plastic and Reconstructive Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan,

3 Graduate School of Health Sciences, Hokkaido University, Sapporo, Japan

Cellular senescence is a biological mechanism that prevents abnormal cell proliferation during tissue repair, and it is often accompanied by the secretion of various factors, such as cytokines and chemokines, known as the senescenceassociated secretory phenotype (SASP). SASP-mediated cell-to-cell communication promotes tissue repair, regeneration, and development. However, senescent cells can accumulate abnormally at injury sites, leading to excessive inflammation, tissue dysfunction, and intractable wounds. The effects of cellular senescence on skin wound healing can be both beneficial and detrimental, depending on the condition. Here, we reviewed the functional differences in cellular senescence that emerge during wound healing, chronic inflammation, and skin aging. We also review the latest mechanisms of wound healing in the epidermis, dermis, and subcutaneous fat, with a focus on cellular senescence, chronic inflammation, and tissue regeneration. Finally, we discuss the potential clinical applications of promoting and inhibiting cellular senescence to maximize benefits and minimize detrimental effects.

KEYWORDS

cellular senescence, senescence-associated secretory phenotypes (SASP), woundhealing, aged-skin, diabetic skin

EDITED BY

Chengliang Deng, Affiliated Hospital of Zunyi Medical University, China

REVIEWED BY

Eleni Mavrogonatou, National Centre of Scientific Research Demokritos, Greece Mariaceleste Aragona, University of Copenhagen, Denmark

*CORRESPONDENCE Takako S. Chikenji, 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 Yuki Saito, 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

RECEIVED 25 November 2023

ACCEPTED 05 February 2024

PUBLISHED 19 February 2024

CITATION

Kita A, Yamamoto S, Saito Y and Chikenji TS (2024), Cellular senescence and wound healing in aged and diabetic skin. Front. Physiol. 15:1344116.

doi: 10.3389/fphys.2024.1344116

© 2024 Kita, Yamamoto, Saito and Chikenji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

Macrocystis pyrifera ferment-containing creams for optimizing facial skin rejuvenation

细胞衰老与衰老相关疾病研究进展

田潇雨卢娜

中国药科大学，中国·江苏南京 210000

摘要

衰老(Senecence)是细胞功能逐渐退化的一种状态，在这种状态下细胞几乎丧失复制能力，并且细胞周期抑制基因p16INK4a 的表达升高。细胞衰老贯穿生物个体的整个生命过程，在各种生理以及病理过程中发挥重要的作用。一方面，衰老的细胞能够促进胚胎发育，伤口愈合和宿主免疫反应以及抑制肿瘤发生发展等。另一方面，随着年龄增长而在体内积累的衰老细胞也会对机体带来有害的影响。这些不能增殖的细胞产生衰老相关分泌表型(Senescence-Associated Secretory PhenotypeSASP)，促进衰老相关疾病(Aging-related Diseae)的发生发展，而清除衰老细胞能够减缓衰老相关疾病的症状。因此寻找能够特异性杀死衰老细胞的药物(Senolytics)成为了抗衰老领域的研究重点。

关键词
细胞衰老;衰老相关分泌表型;衰老相关疾病;抗衰老;Senolytics

Advances in Research on Senescence in Health and Diseases

Xiaoyu Tian Na Lu

China Pharmaceutical University, Nanjing, Jiangsu, 210000, China

AbstractSenescence is a state in which the cell's functional characteristics are gradually deteriorating, in which the cell is at a sustained lowevel ofreplication and is accompanied by an increase in the expression of the cell cycle inhibitor pl6lNK4a The production of senescent cells occurs throughout life and plays key roles in various physiological and pathological proceses. These noneproliferating celsoccupy key cellular niches and produce senescence-associated secretory phenotype (SASP) which contributes to aging-related diseasesprogress. Therefore, the search for Senolytics has become the focus ofresearch in the field of anti-aging.

Keywords
cellular senescence, SASP, aging-related disease, anti-senescence, senolytics

第3页共393页

K2 Content

GLP1R Gene Expression and Kidney Disease Progression 2024-11-04 00:00

Jefferson L. Triozzi, MD, MSCI; Zhihong Yu, MS, PhD; Ayush Giri, MS, PhD; Hua-Chang Chen, PhD; Otis D. Wilson, BBA; Brian Ferolito, MS; T. Alp Ikizler, MD; Elvis A. Akwo, MD, MS; Cassianne Robinson-Cohen, PhD; John Michael Gaziano, MD, MPH; Kelly Cho, PhD, MPH; Lawrence S. Phillips, MD; Ran Tao, PhD; Alexandre C. Pereira, MD, PhD; Adriana M. Hung, MD, MPH; for the VA Million Veteran Program

Key Points

Question Are glucagon-like peptide 1 receptor agonists (GLP-1RAs) associated with kidney disease progression?

Findings In this genetic association study of 353 153 adults, higher genetic GLP1R gene expression as a proxy for GLP-1RAs was associated with a small reduction in the risk of kidney disease progression, even after adjusting for obesity and diabetes.

Meaning These findings support a nephroprotective role of GLP-1RAs.

Abstract

IMPORTANCE Glucagon-like peptide 1 receptor agonists (GLP-1RAs) may have nephroprotective properties beyond those related to weight loss and glycemic control.

OBJECTIVE To investigate the association of genetically proxied GLP-1RAs with kidney disease

DESIGN, SETTING, AND PARTICIPANTS This genetic association study assembled a national retrospective cohort of veterans aged 18 years or older from the US Department of Veterans Affairs Million Veteran Program between January 10, 2011, and December 31, 2021. Data were analyzed from November 2023 to February 2024.

EXPOSURES Genetic risk score for systemic GLP1R gene expression that was calculated for each study participant based on genetic variants associated with GLP1R mRNA levels across all tissue samples within the Genotype-Tissue Expression project.

MAIN OUTCOMES AND MEASURES The primary composite outcome was incident end-stage kidney disease or a 40% decline in estimated glomerular filtration rate. Cox proportional hazards regression survival analysis assessed the association between genetically proxied GLP-1RAs and kidney disease progression.

RESULTS Among 353 153 individuals (92.5% men), median age was 66 years (IQR, 58.0-72.0 years) and median follow-up was 5.1 years (IQR, 3.1-7.2 years). Overall, 25.7% had diabetes, and 45.0% had obesity. A total of 4.6% experienced kidney disease progression. Overall, higher genetic GLP1R gene expression was associated with a lower risk of kidney disease progression in the unadjusted model (hazard ratio [HR], 0.96; 95% CI, 0.92-0.99; P = .02) and in the fully adjusted model accounting for baseline patient characteristics, body mass index, and the presence or absence of diabetes (HR, 0.96; 95% CI, 0.92-1.00; P = .04). The results were similar in sensitivity analyses stratified by diabetes or obesity status.

CONCLUSIONS AND RELEVANCE In this genetic association study, higher GLP1R gene expression was associated with a small reduction in risk of kidney disease progression. These findings support pleiotropic nephroprotective mechanisms of GLP-1RAs independent of their effects on body weight and glycemic control.
Use of Retinoids in Topical Antiaging Treatments: A Focused Review of Clinical Evidence for Conventional and Nanoformulations 2024-10-31 00:00

Daniela Milosheska . Robert Roskar

Received: August 17, 2022 / Accepted: September 6, 2022 / Published online: October 11, 2022

©The Author(s) 2022

ABSTRACT

Nowadays, numerous skincare routines are used to rejuvenate aging skin. Retinoids are one of the most popular ingredients used in antiaging treatments. Among the representatives of retinoids, tretinoin is considered the most effective agent with proven antiaging effects on the skin and can be found in formulations approved as medicines for topical treatment of acne, facial wrinkles, and hyperpigmentation. Other retinoids present in topical medicines are used for various indications, but only tazarotene is also approved as adjunctive agent for treatment of facial fine wrinkling and pigmentation. The most commonly used retinoids such as retinol, retinaldehyde, and retinyl palmitate are contained in cosmeceuticals regulated as cosmetics. Since clinical efficacy studies are not required for marketing cosmetic formulations, there are concerns about the efficacy of these retinoids.

From a formulation perspective, retinoids pose a challenge to researchers as a result of their proven instability, low penetration, and potential for skin irritation. Therefore, novel delivery systems based on nanotechnology are being developed to overcome the limitations of conventional formulations and improve user compliance. In this review, the clinical evidence for retinoids in conventional and nanoformulations for topical antiaging treatments was evaluated. In addition, an overview of the comparison clinical trials between tretinoin and other retinoids is presented. In general, there is a lack of evidence from properly designed clinical trials to support the claimed efficacy of the most commonly used retinoids as antiaging agents in cosmeceuticals. Of the other retinoids contained in medicines, tazarotene and adapalene have clinically evaluated antiaging effects compared to tretinoin and may be considered as potential alternatives for antiaging treatments. The promising potential of retinoid nanoformulations requires a more comprehensive evaluation with additional studies to support the preliminary findings.

Keywords: Antiaging; Clinical evidence; Cosmeceuticals; Nanoformulations; Retinoids; Retinol; Tretinoin

Key Summary Points

Tretinoin is the retinoid present in medicines for topical application with the strongest clinical evidence of antiaging Tazarotene and adapalene may be considered as tretinoin alternatives for antiaging treatments.

Clinical evidence is lacking for retinoids contained in cosmeceuticals for topical antiaging treatments.

Novel formulations based on nanotechnology are being developed to overcome the major drawbacks of retinoid Further evaluation with in vivo testing and clinical trials are needed to support the preclinical results for the developed nanoformulations containing retinoids.

D. Milosheska INSLAB, Maribor, Slovenia

R. Roskar (&)

University of Ljubljana, Faculty of Pharmacy, Askerceva cesta 7, 1000 Ljubljana, Slovenia

e-mail: 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。
Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations 2024-10-30 00:00

Gérald J. Prud’homme1,2 *, Mervé Kurt 2 and Qinghua Wang3,4

1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada,

2 Department of Laboratory Medicine, Keenan Research Centre for Biomedical Science, Unity Health Toronto, Toronto, ON, Canada,

3 Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China,

4 Shanghai Yinuo Pharmaceutical Co., Ltd., Shanghai, China

Edited by:

Cátia F. Lourenço, University of Coimbra, Portugal

Reviewed by:

Mujib Ullah, Stanford University, United States Taylor Landry, East Carolina University, United States

*Correspondence:

Gérald J. Prud’homme 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。

Specialty section:

This article was submitted to Molecular Mechanisms of Aging, a section of the journal Frontiers in Aging

Received: 28 April 2022

Accepted: 06 June 2022

Published: 12 July 2022

Citation:

Prud’homme GJ, Kurt M and Wang Q (2022) Pathobiology of the Klotho Antiaging Protein and Therapeutic Considerations. Front. Aging 3:931331.

doi: 10.3389/fragi.2022.931331

The α-Klotho protein (henceforth denoted Klotho) has antiaging properties, as first observed in mice homozygous for a hypomorphic Klotho gene (kl/kl). These mice have a shortened lifespan, stunted growth, renal disease, hyperphosphatemia, hypercalcemia, vascular calcification, cardiac hypertrophy, hypertension, pulmonary disease, cognitive impairment, multi-organ atrophy and fibrosis. Overexpression of Klotho has opposite effects, extending lifespan. In humans, Klotho levels decline with age, chronic kidney disease, diabetes, Alzheimer’s disease and other conditions. Low Klotho levels correlate with an increase in the death rate from all causes. Klotho acts either as an obligate coreceptor for fibroblast growth factor 23 (FGF23), or as a soluble pleiotropic endocrine hormone (s-Klotho). It is mainly produced in the kidneys, but also in the brain, pancreas and other tissues. On renal tubular-cell membranes, it associates with FGF receptors to bind FGF23. Produced in bones, FGF23 regulates renal excretion of phosphate (phosphaturic effect) and vitamin D metabolism. Lack of Klotho or FGF23 results in hyperphosphatemia and hypervitaminosis D. With age, human renal function often deteriorates, lowering Klotho levels. This appears to promote age-related pathology. Remarkably, Klotho inhibits four pathways that have been linked to aging in various ways: Transforming growth factor β (TGF-β), insulin-like growth factor 1 (IGF-1), Wnt and NF-κB. These can induce cellular senescence, apoptosis, inflammation, immune dysfunction, fibrosis and neoplasia. Furthermore, Klotho increases cell-protective antioxidant enzymes through Nrf2 and FoxO. In accord, preclinical Klotho therapy ameliorated renal, cardiovascular, diabetes-related and neurodegenerative diseases, as well as cancer. s-Klotho protein injection was effective, but requires further investigation. Several drugs enhance circulating Klotho levels, and some cross the blood-brain barrier to potentially act in the brain. In clinical trials, increased Klotho was noted with renin-angiotensin system inhibitors (losartan, valsartan), a statin (fluvastatin), mTOR inhibitors (rapamycin, everolimus), vitamin D and pentoxifylline. In preclinical work, antidiabetic drugs (metformin, GLP-1-based, GABA, PPAR-γ agonists) also enhanced Klotho. Several traditional medicines and/or nutraceuticals increased Klotho in rodents, including astaxanthin, curcumin, ginseng, ligustilide and resveratrol. Notably, exercise and sport activity increased Klotho. This review addresses molecular, physiological and therapeutic aspects of Klotho.

Keywords: aging, FGF23, hyperphosphatemia, klotho, IGF-1, NF-KappaB, TGF-beta, Wnt

Custom Mod Mega1

主任医师、教授、博导，南方医科大学第三附属医院（广东省骨科医院）院长

文献精选

Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics

Cellular senescence and wound healing in aged and diabetic skin

Macrocystis pyrifera ferment-containing creams for optimizing facial skin rejuvenation

细胞衰老与衰老相关疾病研究进展

学术会议

伤口世界提示

Custom Mod Mega1

主任医师、教授、博导，南方医科大学第三附属医院（广东省骨科医院）院长

文献精选

Diverse Roles of Cellular Senescence in Skeletal Muscle Inflammation, Regeneration, and Therapeutics

Cellular senescence and wound healing in aged and diabetic skin

Macrocystis pyrifera ferment-containing creams for optimizing facial skin rejuvenation

细胞衰老与衰老相关疾病研究进展

消息订阅

学术会议

伤口世界提示