细胞衰老与衰老相关疾病研究进展

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16 10月 2024

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Author : 伤口世界

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

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The efcacy of hyaluronic acid fragments with amino acid in combating facial skin aging: an ultrasound and histological study 2024-11-05 00:00

Antonio Scarano1 · E. Qorri2 · A. Sbarbati3 · S. A. Gehrke4 · Alessio Frisone1 · D. Amuso3 · Sergio Rexhep Tari1

Received: 30 March 2024 / Accepted: 17 May 2024 / Published online: 24 June 2024

© The Author(s) 2024

Antonio Scarano

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E. Qorri

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A. Sbarbati

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S. A. Gehrke

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D. Amuso

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Sergio Rexhep Tari

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1 Department of Medical, Oral and Biotechnological Sciences, University of Chieti-Pescara, Strada Marcello Mucci 38/B, 66100 Chieti, Italy

2 Department of Dentistry, Faculty of Medical Sciences, Albanian University, 1001 Tirana, Albania

3 Department of Neurosciences, Biomedicine and Movement Sciences, Anatomy and Histology Section, School of Medicine, University of Verona, Verona, Italy

4 Department of Research, Bioface/PgO/UCAM, Montevideo, Uruguay

Abstract

Background Various techniques have been employed in aesthetic medicine to combat skin aging, in particular that of the facial region. Hyaluronic acid is utilized to enhance moisture levels and extracellular matrix molecules. This study aims to histologically assess the efects of low molecular weight hyaluronic acid fragments combined with amino acids (HAAM) on facial skin rejuvenation through intradermal microinjections.

Methods A total of twenty women, with an average age of 45 and ranging from 35 to 64 years old, participated in the study, including 8 in menopause and 12 in the childbearing age group. Mesotherapy was used to administer HAAM to the patients. Prior to and three months after the treatment, each patient underwent small circular punch biopsies. Ultrasound examinations were conducted using B-mode, capturing 2D images in longitudinal or transverse orientations with frequencies ranging from 5 to 13 Mega-hertz (MY LAB X8, ESAOTE, Genova, Italy). A total of 60 ultrasound examinations were taken, with 30 collected before treatment and 30 after treatment.

Results The histological analysis demonstrates an increase in fbroblast activity resulting in the production of Type III reticular collagen, as well as an increased number of blood vessels and epidermal thickness. However, the analysis of ultrasound data before and after treatment showed no statistical diference in skin thickness in malar area, chin and mandibular angle.

Conclusions Histological assessments indicate that subcutaneous infltration of HAAM has a substantial impact on the dermis of facial skin.

Keywords Hyaluronic acid · Hyaluronic acid fragments · Amino acid · Fibroblast · Skin aging · Ultrasound
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

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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