Mechanisms of Ageing and Development最新文献

The relationship between physical activity and telomere length in women: A systematic review

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-19 DOI: 10.1016/j.mad.2025.112042

Jeni Page , Catherine Stephens , Melissa Richard , Elizabeth Lyons , Elizabeth Baumler , M. Terese Verklan , Elizabeth Lorenzo

Telomere length (TL) is a biomarker of cellular aging with variations observed by sex, age, race, and ethnicity. Prior studies have suggested that physical activity (PA) may positively impact TL by potentially elongating telomeres and slowing cellular aging. However, research examining the optimal type and intensity of PA needed to elicit these changes specific to women remains limited. This systematic review aimed to investigate variations in TL in response to PA among women, exploring how these effects differ by age, race, or ethnicity. Following PRISMA guidelines, searches across five databases identified 17 relevant studies published from 2008 to 2022. A narrative synthesis of study findings indicated PA did not have a significant relationship with TL in women. However, a possible positive relationship was noted between specific types of PA and TL, specific to combined aerobic and strength-training PA and high intensity interval training interventions. The impact of PA on TL appeared to be age-dependent as well, showing significant positive relationships between PA and TL in early and later adulthood but not in middle adulthood. Findings related to race or ethnicity were inconclusive due to limited analyses from the included studies. The studies varied greatly by PA type, intensity, duration, and frequency, which, along with the reliance on self-reported PA measures in the observational studies, impacted the ability to draw firm conclusions. This review underscores the necessity for future research in large cohort studies using objectively measured PA interventions to further clarify the complex associations between PA and TL in women.

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引用次数: 0

Vascular participation in bone healing: Implications related to advancing age and morbidity

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-14 DOI: 10.1016/j.mad.2025.112041

Rhonda D. Prisby

Fracture non-union and the related morbidities represent a global health concern. While many factors are necessary for proper bone healing following fracture, the vascular system is requisite. Important considerations include vascular morphology in bone and marrow and the regulation of tissue blood flow. This review discusses the types of fracture management and associated bone repair (i.e., intramembranous vs. endochondral), the phases of bone healing, and the role of the bone vascular network. Finally, fracture healing is considered in the context of advanced age and morbidity.

引用次数: 0

Aging: A struggle for beneficial to overcome negative factors made by muscle and bone 衰老：克服肌肉和骨骼造成的负面因素的有益斗争

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-12 DOI: 10.1016/j.mad.2025.112039

Steven S. Welc , Marco Brotto , Kenneth E. White , Lynda F. Bonewald

Musculoskeletal health is strongly influenced by regulatory interactions of bone and muscle. Recent discoveries have identified a number of key mechanisms through which soluble factors released during exercise by bone exert positive effects on muscle and by muscle on bone. Although exercise can delay the negative effects of aging, these beneficial effects are diminished with aging. The limited response of aged muscle and bone tissue to exercise are accompanied by a failure in bone and muscle communication. Here, we propose that exercise induced beneficial factors must battle changes in circulating endocrine and inflammatory factors that occur with aging. Furthermore, sedentary behavior results in the release of negative factors impacting the ability of bone and muscle to respond to physical activity especially with aging. In this review we report on exercise responsive factors and evidence of modification occurring with aging.

引用次数: 0

Oral frailty indicators and cardio- and cerebrovascular diseases in older age: A systematic review 老年人口腔虚弱指标与心脑血管疾病：系统综述。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112010

Vittorio Dibello , Frank Lobbezoo , Francesco Panza , Madia Lozupone , Alberto Pilotto , Vitalba Vitale , Carlo Custodero , Antonio Dibello , Vincenzo Vertucci , Antonio Daniele , Daniele Manfredini , Vincenzo Solfrizzi

Oral health indicators may contribute to the oral frailty phenotype, an age-related gradual loss of oral function together with a decline in cognitive and physical functions. The present systematic review synthetized current knowledge on the associations of oral frailty indicators and major cardio- and cerebrovascular diseases in older age, including coronary heart disease (CHD), arteriosclerosis, arrhythmias, hypertension, cardiovascular diseases not otherwise specified (NOS), and stroke. The study is registered on PROSPERO-(CRD42023397932). From database inception to March 31, 2024, six different electronic databases were consulted assessing the eligibility of 50,005 records against the inclusion criteria and 20 studies on 226,025 older adults were included. Five different indicators of oral frailty (number of teeth, periodontal disease, general oral health, dry mouth, and bite force) were related to cardio- and cerebrovascular diseases. The number of teeth was associated with all the outcomes except hypertension, followed by periodontal disease associated with CHD, arteriosclerosis, hypertension, and stroke. General oral health and dry mouth were associated with CHD/arrhythmias and CHD/stroke, respectively. Finally, bite force was associated only with cardiovascular diseases NOS. The present findings could help to assess the contribution of each oral frailty indicator to the development of cardio- and cerebrovascular diseases in older age.

口腔健康指标可能导致口腔脆弱表型，这是一种与年龄相关的口腔功能逐渐丧失以及认知和身体功能下降。本系统综述综合了目前关于口腔脆弱指标与老年人主要心脑血管疾病（包括冠心病、动脉硬化、心律失常、高血压、非特指心血管疾病（NOS）和脑卒中）相关的知识。该研究已在PROSPERO-(CRD42023397932)注册。从数据库建立到2024年3月31日，我们参考了6个不同的电子数据库，评估了50,005条记录是否符合纳入标准，并纳入了20项研究，涉及226,025名老年人。口腔虚弱的五项不同指标（牙齿数量、牙周病、口腔总体健康、口干和咬合力）与心脑血管疾病有关。除高血压外，牙齿数量与所有结果相关，其次是伴有冠心病的牙周病、动脉硬化、高血压和中风。一般口腔健康和口干分别与冠心病/心律失常和冠心病/中风相关。最后，咬合力仅与心血管疾病NOS相关。本研究结果有助于评估各口腔脆弱指标对老年心脑血管疾病发展的贡献。

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引用次数: 0

Senolytics rejuvenate aging cardiomyopathy in human cardiac organoids 老年性药物使人类心脏类器官老化的心肌病恢复活力。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112007

Mariangela Scalise , Eleonora Cianflone , Claudia Quercia , Loredana Pagano , Antonio Chiefalo , Antonio Stincelli , Annalaura Torella , Barbara Puccio , Gianluca Santamaria , Hiram P. Guzzi , Pierangelo Veltri , Antonella De Angelis , Konrad Urbanek , Georgina M. Ellison-Hughes , Daniele Torella , Fabiola Marino

Background

Human cardiac organoids closely replicate the architecture and function of the human heart, offering a potential accurate platform for studying cellular and molecular features of aging cardiomyopathy. Senolytics have shown potential in addressing age-related pathologies but their potential to reverse aging-related human cardiomyopathy remains largely unexplored.

Methods

We employed human iPSC-derived cardiac organoids (hCOs/hCardioids) to model doxorubicin(DOXO)-induced cardiomyopathy in an aged context. hCardioids were treated with DOXO and subsequently with a combination of two senolytics: dasatinib (D) and quercetin (Q).

Results

DOXO-treated hCardioids exhibited significantly increased oxidative stress, DNA damage (pH2AX), cellular senescence (p16^INK4A) and decreased cell proliferation associated with a senescence-associated secretory phenotype (SASP). DOXO-treated hCardioids were considerably deprived of cardiac progenitors and displayed reduced cardiomyocyte proliferation as well as contractility. These distinctive aging-associated characteristics were confirmed by global RNA-sequencing analysis. Treatment with D+Q reversed these effects, reducing oxidative stress and senescence markers, alleviating SASP, and restoring hCardioids viability and function. Additionally, senolytics replenished cardiac progenitors and reversed the cardiomyocyte proliferation deficit.

Conclusions

Doxorubicin triggers an age-associated phenotype in hCardioids reliably modelling the main cellular and molecular features of aging cardiomyopathy. Senescence is a key mechanism of the aged-hCOs phenotype as senolytics rejuvenated aged-hCardioids restoring their structure and function while reverting the age-associated regenerative deficit.

背景：人类心脏类器官与人类心脏的结构和功能紧密复制，为研究衰老性心肌病的细胞和分子特征提供了一个潜在的准确平台。老年性药物在解决与年龄相关的病理方面显示出潜力，但其逆转与年龄相关的人类心肌病的潜力仍未得到很大程度的探索。方法：我们使用人类ipsc衍生的心脏类器官（hCOs/hCardioids）来模拟阿霉素（DOXO）诱导的老年心肌病。结果：DOXO处理的hCardioids表现出明显的氧化应激、DNA损伤（pH2AX）、细胞衰老（p16INK4A）以及与衰老相关的分泌表型（SASP）相关的细胞增殖降低。doxo处理的类心肌细胞明显缺乏心脏祖细胞，心肌细胞增殖和收缩能力降低。这些独特的衰老相关特征被全球rna测序分析证实。D+Q治疗逆转了这些作用，降低了氧化应激和衰老标志物，缓解了SASP，恢复了类心细胞的活力和功能。此外，老年药补充心脏祖细胞并逆转心肌细胞增殖缺陷。结论：阿霉素在类心脏中触发一种与年龄相关的表型，可靠地模拟了衰老性心肌病的主要细胞和分子特征。衰老是衰老型hcos表型的关键机制，因为抗衰老药物使衰老的类心脏恢复其结构和功能，同时恢复与年龄相关的再生缺陷。

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引用次数: 0

Single-cell analysis of human peripheral blood reveals high immune response activity in successful ageing individuals 人类外周血的单细胞分析揭示了成功衰老个体的高免疫反应活性。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112011

Yu Wang , Yuxing Zhang , Ge Gong , Quanzhong Liu , Liangyu Li , Mingjiong Zhang , Shuping Shen , Ran Wang , Jianqing Wu , Wei Xu

Beneficial remodeling of the immune system in successful ageing individuals (centenarians and supercentenarians) is critical for healthy ageing. However, mechanisms for dynamic regulation of immunity during ageing remain unclear. We use single-cell RNA sequencing (scRNA-seq) as an analytical strategy to study the dynamic regulation of immunity during aging and its molecular mechanisms at the single-cell level. We performed an integrative analysis of 87,215 peripheral blood mononuclear cells, from seven supercentenarians, three centenarians, and four elderly controls, generated by single-cell transcriptomics complemented with fluorescence-activated cell sorting. Animals experiments were also conducted to validate the makers of healthy aging found by our bioinformatic analysis and further explore the dynamic of immune changes during aging process. We found that CD8⁺ effector memory T cells and terminally differentiated B cells were enriched in the longevity group (centenarians and supercentenarians), whereas naïve T cells and Tregs were enriched in elderly controls. CD56^dim NK cells in the longevity group activated Fc-γ receptor signaling. The higher antigen-presenting ability of CD14⁺ monocytes in the longevity group and the CellChat analysis indicated that CD14⁺ monocytes might assist active T and B cells. Here, we revealed the adaptive immune remodeling geromarkers of immunosenescence in centenarians and supercentenarians, which could be considered as biomarkers of healthy aging, and might help sustain immune responses and achieve exceptional longevity.

成功衰老个体（百岁老人和超级百岁老人）免疫系统的有益重塑对健康衰老至关重要。然而，衰老过程中免疫动态调节的机制尚不清楚。我们使用单细胞RNA测序（scRNA-seq）作为分析策略，在单细胞水平上研究衰老过程中免疫的动态调控及其分子机制。我们对来自7名超级百岁老人、3名百岁老人和4名老年对照者的87,215个外周血单个核细胞进行了综合分析，这些细胞是通过单细胞转录组学和荧光激活细胞分选相结合产生的。通过动物实验验证生物信息学分析发现的健康衰老因素，进一步探讨衰老过程中免疫变化的动态。我们发现CD8+效应记忆T细胞和终末分化B细胞在长寿组（百岁老人和超百岁老人）中富集，而naïve T细胞和Tregs在老年对照组中富集。长寿组CD56dim NK细胞激活Fc-γ受体信号。长寿组中CD14+单核细胞更高的抗原呈递能力和CellChat分析表明，CD14+单核细胞可能有助于活跃的T细胞和B细胞。本研究揭示了百岁老人和超百岁老人免疫衰老的适应性免疫重塑标记，这些标记可以被认为是健康衰老的生物标记，可能有助于维持免疫反应并实现超长寿命。

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引用次数: 0

Role of chemokines in aging and age-related diseases 趋化因子在衰老和年龄相关疾病中的作用。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112009

Jitendra Kumar Chaudhary , Ajay Kumar Danga , Anita Kumari , Akshay Bhardwaj , Pramod C. Rath

Chemokines (chemotactic cytokines) play essential roles in developmental process, immune cell trafficking, inflammation, immunity, angiogenesis, cellular homeostasis, aging, neurodegeneration, and tumorigenesis. Chemokines also modulate response to immunotherapy, and consequently influence the therapeutic outcome. The mechanisms underlying these processes are accomplished by interaction of chemokines with their cognate cell surface G protein-coupled receptors (GPCRs) and subsequent cellular signaling pathways. Chemokines play crucial role in influencing aging process and age-related diseases across various tissues and organs, primarily through inflammatory responses (inflammaging), recruitment of macrophages, and orchestrated trafficking of other immune cells. Chemokines are categorized in four distinct groups based on the position and number of the N-terminal cysteine residues; namely, the CC, CXC, CX3C, and (X)C. They mediate inflammatory responses, and thereby considerably impact aging process across multiple organ-systems. Therefore, understanding the underlying mechanisms mediated by chemokines may be of crucial importance in delaying and/or modulating the aging process and preventing age-related diseases. In this review, we highlight recent progress accomplished towards understanding the role of chemokines and their cellular signaling pathways involved in aging and age-relaed diseases of various organs. Moreover, we explore potential therapeutic strategies involving anti-chemokines and chemokine receptor antagonists aimed at reducing aging and mitigating age-related diseases. One of the modern methods in this direction involves use of chemokine receptor antagonists and anti-chemokines, which suppress the pro-inflammatory response, thereby helping in resolution of inflammation. Considering the wide-spectrum of functional involvements of chemokines in aging and associated diseases, several clinical trials are being conducted to develop therapeutic approaches using anti-chemokine and chemokine receptor antagonists to improve life span and promote healthy aging.

趋化因子（趋化因子）在发育过程、免疫细胞运输、炎症、免疫、血管生成、细胞稳态、衰老和肿瘤发生等方面发挥着重要作用。趋化因子也调节对免疫治疗的反应，从而影响治疗结果。这些过程的机制是通过趋化因子与其同源细胞表面G蛋白偶联受体（gpcr）和随后的细胞信号通路的相互作用来完成的。趋化因子在影响各种组织和器官的衰老过程和与年龄相关的疾病中起着至关重要的作用，主要是通过炎症反应（炎症）、巨噬细胞的募集和其他免疫细胞的协调运输。根据n端半胱氨酸残基的位置和数量，趋化因子可分为四组；即CC、CXC、CX3C、(X)C。它们介导炎症反应，从而在很大程度上影响多个器官系统的衰老过程。因此，了解趋化因子介导的潜在机制可能对延缓和/或调节衰老过程和预防与年龄相关的疾病至关重要。在这篇综述中，我们重点介绍了在了解趋化因子及其细胞信号通路在衰老和各器官年龄相关疾病中的作用方面取得的最新进展。此外，我们探索潜在的治疗策略，包括趋化因子和趋化因子受体拮抗剂，旨在减少衰老和减轻与年龄相关的疾病。这方面的现代方法之一涉及使用趋化因子受体拮抗剂和抗趋化因子，它们抑制促炎反应，从而帮助解决炎症。考虑到趋化因子在衰老和相关疾病中的广泛功能参与，一些临床试验正在进行，以开发使用趋化因子受体拮抗剂的治疗方法，以延长寿命并促进健康衰老。

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引用次数: 0

Aberrant expression of messenger and small noncoding RNAomes in aged skin of rats 衰老大鼠皮肤中信使和小非编码rna的异常表达。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112022

Danyang Zhao , Yu Wang , Chuandong Wang , Yaxin Xue , Hao Lv , Wei Xu , Dong Han , Yu Sun , Qingfeng Li

The exact mechanisms and key functional molecules involved in skin ageing remain largely unknown. Studies linking the expression of messenger RNAs (mRNAs) and small noncoding RNAs (sncRNAs) to skin ageing are limited. In this study, we performed RNA sequencing to assess the effects of ageing on the expression of mRNAs and sncRNAs in rat skin. Our results revealed that 241 mRNAs, 109 microRNAs (miRNAs), 20 piwi-interacting RNAs (piRNAs), 45 small nucleolar RNAs (snoRNAs), and 7 small nuclear RNAs (snRNAs) were significantly differentially expressed in the skin of aged rats compared to their younger counterparts. Histological validation using RT-qPCR further verified the significant differential expression of 13 mRNAs, 7 miRNAs, 2 piRNAs, 15 snoRNAs, and 1 snRNA. Additionally, several sncRNAs showed differential expression across various tissues, suggesting that they may have broad correlations with ageing. After establishing cellular senescence in skin fibroblasts, we identified 4 mRNAs, 4 miRNAs, and 10 snoRNAs that may mediate skin ageing by modulating fibroblast senescence. Notably, overexpression or knockdown of some differentially expressed RNAs in fibroblasts influenced cellular senescence, indicating that these RNAs could play an important role in the skin ageing process. These findings highlight their potential significance for future treatments of age-related skin disorders.

皮肤老化的确切机制和关键功能分子在很大程度上仍然未知。将信使rna （mrna）和小非编码rna （sncRNAs）的表达与皮肤老化联系起来的研究是有限的。在这项研究中，我们进行了RNA测序，以评估衰老对大鼠皮肤mrna和sncRNAs表达的影响。我们的研究结果显示，与年轻大鼠相比，老年大鼠皮肤中有241种mrna、109种microRNAs （miRNAs）、20种piwi相互作用rna （piRNAs）、45种小核核rna （snoRNAs）和7种小核rna （snrna）的表达存在显著差异。RT-qPCR进一步验证了13个mrna、7个mirna、2个pirna、15个snorna和1个snRNA的显著差异表达。此外，一些sncrna在不同组织中表现出差异表达，这表明它们可能与衰老有广泛的相关性。在皮肤成纤维细胞中建立细胞衰老后，我们鉴定了4种mrna、4种mirna和10种snorna，它们可能通过调节成纤维细胞衰老来介导皮肤衰老。值得注意的是，成纤维细胞中一些差异表达rna的过表达或敲低会影响细胞衰老，这表明这些rna可能在皮肤衰老过程中发挥重要作用。这些发现强调了它们对未来治疗与年龄有关的皮肤疾病的潜在意义。

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引用次数: 0

Molecular mechanisms and potential interventions during aging-associated sarcopenia 衰老相关肌肉减少症的分子机制和潜在干预措施。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112020

Xiaoqin Luo , Jin Wang , Qingqing Ju , Tianyu Li , Xiuli Bi

Sarcopenia, a common condition observed in the elderly, presenting a significant public health challenge due to its high prevalence, insidious onset and diverse systemic effects. Despite ongoing research, the precise etiology of sarcopenia remains elusive. Aging-related processes, which included inflammation, oxidative stress, compromised mitochondrial function and apoptosis, have been implicated in its development. Notably, effective pharmacological treatments for sarcopenia are currently lacking, highlighting the necessity for a deeper understanding of its pathogenesis and causative factors to enable proactive interventions. This article is aimed to provide an extensive overview of the pathogenesis of sarcopenia, along with a summary of current treatment and prevention strategies.

肌肉疏松症是一种常见于老年人的疾病，由于其发病率高、起病隐匿和对全身产生多种影响，给公共卫生带来了重大挑战。尽管研究仍在进行，但肌肉疏松症的确切病因仍难以捉摸。与衰老相关的过程，包括炎症、氧化应激、线粒体功能受损和细胞凋亡，都与肌少症的发生有关。值得注意的是，目前还缺乏治疗肌肉疏松症的有效药物，因此有必要深入了解其发病机制和致病因素，以便采取积极干预措施。本文旨在广泛概述肌肉疏松症的发病机制，并总结当前的治疗和预防策略。

引用次数: 0

The telomere connection between aging and cancer: The burden of replication stress and dysfunction 衰老和癌症之间的端粒关系：复制压力和功能障碍的负担。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2025.112026

Virginia Boccardi , Luigi Marano

Aging is a complex process that affects individuals at the molecular, cellular, tissue, and systemic levels, arising from the cumulative effects of damage and reduced repair mechanisms. This process leads to the onset of age-related diseases, including cancer, which exhibits increased incidence with age. Telomeres, the protective caps at chromosome ends, play a crucial role in genome stability and are closely connected with aging and age-related disorders. Both excessively short and long telomere lengths may contribute to cancer development when their balance is disrupted. Fragile telomeres, characterized by abnormalities and replication stress, may provide novel insights into the connection between aging and cancer. The accumulation of fragile telomeres, possibly due to intense replicative stress, may represent a key factor. Given the dynamic nature of telomeres, large longitudinal studies are essential for understanding their role in aging and cancer susceptibility, which is crucial for developing effective strategies to promote healthy aging and mitigate cancer risk.

衰老是一个复杂的过程，它在分子、细胞、组织和系统水平上影响个体，是由损伤和修复机制减弱的累积效应引起的。这一过程导致与年龄有关的疾病，包括癌症的发病，其发病率随着年龄的增长而增加。端粒是染色体末端的保护帽，在基因组稳定中起着至关重要的作用，并与衰老和年龄相关疾病密切相关。当端粒长度的平衡被破坏时，过短和过长都可能导致癌症的发展。脆弱的端粒，以异常和复制压力为特征，可能为衰老和癌症之间的联系提供新的见解。脆弱端粒的积累，可能是由于强烈的复制压力，可能是一个关键因素。考虑到端粒的动态特性，大型纵向研究对于了解它们在衰老和癌症易感性中的作用至关重要，这对于制定促进健康衰老和降低癌症风险的有效策略至关重要。

引用次数: 0