Aging-Us最新文献_第10页

Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing. 局部ABT-263治疗可减少皮肤老化，改善随后的伤口愈合。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-12-03 DOI: 10.18632/aging.206165

Maria Shvedova, Rex Jeya Rajkumar Samdavid Thanapaul, Joy Ha, Jannat Dhillon, Grace H Shin, Jack Crouch, Adam C Gower, Sami Gritli, Daniel S Roh

{"title":"Topical ABT-263 treatment reduces aged skin senescence and improves subsequent wound healing.","authors":"Maria Shvedova, Rex Jeya Rajkumar Samdavid Thanapaul, Joy Ha, Jannat Dhillon, Grace H Shin, Jack Crouch, Adam C Gower, Sami Gritli, Daniel S Roh","doi":"10.18632/aging.206165","DOIUrl":"10.18632/aging.206165","url":null,"abstract":"Senescent cells accumulate in aging tissues, impairing their ability to undergo repair and regeneration following injury. Previous research has demonstrated that targeting tissue senescence with senolytics can enhance tissue regeneration and repair by selectively eliminating SnCs in specific aged tissues. In this study, we focused on eliminating senescent skin cells in aged mice to assess the effects on subsequent wound healing. We applied ABT-263 directly to the skin of 24-month-old mice over a 5-day period. Following topical ABT-263, aged skin demonstrated decreased gene expression of senescence markers p16 and p21, accompanied by reductions in SA-β-gal- and p21-positive cells compared to DMSO controls. However, ABT-263 also triggered a temporary inflammatory response and macrophage infiltration in the skin. Bulk RNA sequencing of ABT-263-treated skin revealed prompt upregulation of genes associated with wound healing pathways, including hemostasis, inflammation, cell proliferation, angiogenesis, collagen synthesis, and extracellular matrix organization. Aged mice skin pre-treated with topical ABT-263 exhibited accelerated wound closure. In conclusion, topical ABT-263 effectively reduced several senescence markers in aged skin, thereby priming the skin for improved subsequent wound healing. This enhancement may be attributed to ABT-263-induced senolysis which in turn stimulates the expression of genes involved in extracellular matrix remodeling and wound repair pathways.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"16 ","pages":"16-32"},"PeriodicalIF":3.9,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781953","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring aortic stiffness in aging mice: a comprehensive methodological overview. 探索老龄小鼠主动脉硬化：全面的方法学综述。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-12-02 DOI: 10.18632/aging.206168

Laetitia Vanalderwiert, Auberi Henry, Juliana Martins de Souza E Silva, Daniel Carvajal-Berrio, Laurent Debelle, Amandine Wahart, Julia Marzi, Katja Schenke-Layland, Gilles Faury, Isabelle Six, Christian E H Schmelzer, Jürgen Brinckmann, Heiko Steenbock, Sébastien Almagro, Frédéric Delacoux, Stéphane Jaisson, Philippe Gillery, Pascal Maurice, Hervé Sartelet, Amar Bennasroune, Laurent Duca, Béatrice Romier, Sébastien Blaise

{"title":"Exploring aortic stiffness in aging mice: a comprehensive methodological overview.","authors":"Laetitia Vanalderwiert, Auberi Henry, Juliana Martins de Souza E Silva, Daniel Carvajal-Berrio, Laurent Debelle, Amandine Wahart, Julia Marzi, Katja Schenke-Layland, Gilles Faury, Isabelle Six, Christian E H Schmelzer, Jürgen Brinckmann, Heiko Steenbock, Sébastien Almagro, Frédéric Delacoux, Stéphane Jaisson, Philippe Gillery, Pascal Maurice, Hervé Sartelet, Amar Bennasroune, Laurent Duca, Béatrice Romier, Sébastien Blaise","doi":"10.18632/aging.206168","DOIUrl":"10.18632/aging.206168","url":null,"abstract":"Stiffening of the vascular network is associated with the early stages of vascular aging, leading to cardiovascular disorders (hypertension), renal failures, or neurodegenerative diseases (Alzheimer's). Unfortunately, many people remain undiagnosed because diagnostic methods are either unsuitable for a large population or unfamiliar to clinicians which favor the hypertension evaluation. In preclinical research, stiffness studies are often partially conducted. We think that the evaluation of aortic stiffness is essential as it would improve our understanding of aging diseases progression. We propose here a systematic method using decision trees in a multi-scale and multimodal approaches. Our method was evaluated by analyzing the aortic situation in old and young mice. We demonstrate that both the endothelial and smooth muscle cells exhibit pronounced functional alterations in favor of constriction. Additionally, there is significant remodeling of the extracellular matrix, leading to a drastic degradation of elastic fibers and the accumulation of collagen in the aortic wall. This series of changes contributes to the development of vascular rigidity, a preliminary stage of arterial hypertension. Our results suggest that our method should improve preclinical understanding and encourage clinicians to equip themselves with tools for assessing vascular function, as it is an essential issue for preventing numerous pathologies.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"280-307"},"PeriodicalIF":3.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Less frequent skin ulcers among patients with Werner syndrome treated with pioglitazone: findings from the Japanese Werner Syndrome Registry. 吡格列酮治疗的维尔纳综合征患者皮肤溃疡发生率较低：来自日本维尔纳综合征登记处的研究结果。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-12-02 DOI: 10.18632/aging.206161

Kazuto Aono, Masaya Koshizaka, Mayumi Shoji, Hiyori Kaneko, Yukari Maeda, Hisaya Kato, Yoshiro Maezawa, Makoto Miyabayashi, Mai Ishikawa, Akiko Sekiguchi, Sei-Ichiro Motegi, Shinji Tsukamoto, Akira Taniguchi, Yukiko Shoda, Toru Yoshimura, Junji Kawashima, Kayo Yoshinaga, Hironori Nakagami, Yoichi Takami, Ken Sugimoto, Kunihiko Hashimoto, Naoki Okubo, Takashi Yoshida, Masato Ohara, Asako Kogure, Daisuke Suzuki, Masafumi Kuzuya, Kazuhisa Watanabe, Minoru Takemoto, Junko Oshima, Koutaro Yokote

{"title":"Less frequent skin ulcers among patients with Werner syndrome treated with pioglitazone: findings from the Japanese Werner Syndrome Registry.","authors":"Kazuto Aono, Masaya Koshizaka, Mayumi Shoji, Hiyori Kaneko, Yukari Maeda, Hisaya Kato, Yoshiro Maezawa, Makoto Miyabayashi, Mai Ishikawa, Akiko Sekiguchi, Sei-Ichiro Motegi, Shinji Tsukamoto, Akira Taniguchi, Yukiko Shoda, Toru Yoshimura, Junji Kawashima, Kayo Yoshinaga, Hironori Nakagami, Yoichi Takami, Ken Sugimoto, Kunihiko Hashimoto, Naoki Okubo, Takashi Yoshida, Masato Ohara, Asako Kogure, Daisuke Suzuki, Masafumi Kuzuya, Kazuhisa Watanabe, Minoru Takemoto, Junko Oshima, Koutaro Yokote","doi":"10.18632/aging.206161","DOIUrl":"10.18632/aging.206161","url":null,"abstract":"Background and aim: Werner syndrome (WS) is an autosomal recessive, adult-onset, progeroid syndrome caused by WRN mutations. As refractory skin ulcers significantly affect the quality of life of patients with WS, this study identified ulcer risk factors and assessed prevention methods.Methods: We analyzed the data of 51 patients with WS enrolled in the Japanese Werner Syndrome Registry between 2016 and 2022. A cross-sectional analysis was performed to determine the association with skin ulcers at baseline. Statistical analyses were conducted, including Welch's and Pearson's chi-square tests. Age was adjusted using a logistic regression model.Results: The mean patient age was 48.8±7.6 years, and 66.7% of patients presented with skin ulcers. Univariate analysis showed that patients with skin ulcers were older than those without ulcers. Systolic blood pressure (SBP) was higher in patients with skin ulcers. Patients without skin ulcers received metformin and pioglitazone treatment significantly more often than those with ulcers. Logistic regression analysis adjusted for age showed that higher SBP remained a significant risk factor for skin ulcers. Patients administered pioglitazone had lower ulcer morbidity.Conclusions: Age and SBP are risk factors for skin ulcers in patients with WS. Moreover, pioglitazone treatment may prevent skin ulcers.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"16 ","pages":"13526-13533"},"PeriodicalIF":3.9,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723649/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction of: miR-34a inhibits melanoma growth by targeting ZEB1. miR-34a通过靶向ZEB1抑制黑色素瘤生长。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-11-30 DOI: 10.18632/aging.206155

Yazhen Xu, Bingyu Guo, Xiaoyan Liu, Kai Tao

引用次数: 0

Correction for: DNA N⁶-methyladenine modification in hypertension. 校正：高血压患者DNA n6 -甲基腺嘌呤修饰。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-11-30 DOI: 10.18632/aging.206154

Ye Guo, Yuqing Pei, Kexin Li, Wei Cui, Donghong Zhang

引用次数: 0

Thermotherapy has sexually dimorphic responses in APP/PS1 mice. 热疗在APP/PS1小鼠中有两性二态反应。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-11-29 DOI: 10.18632/aging.206156

Samuel A McFadden, Mackenzie R Peck, Lindsey N Sime, MaKayla F Cox, Erol D Ikiz, Caleigh A Findley, Kathleen Quinn, Yimin Fang, Andrzej Bartke, Erin R Hascup, Kevin N Hascup

{"title":"Thermotherapy has sexually dimorphic responses in APP/PS1 mice.","authors":"Samuel A McFadden, Mackenzie R Peck, Lindsey N Sime, MaKayla F Cox, Erol D Ikiz, Caleigh A Findley, Kathleen Quinn, Yimin Fang, Andrzej Bartke, Erin R Hascup, Kevin N Hascup","doi":"10.18632/aging.206156","DOIUrl":"10.18632/aging.206156","url":null,"abstract":"A thermoregulatory decline occurs with age due to changes in muscle mass, vasoconstriction, and metabolism that lowers core body temperature (Tc). Although lower Tc is a biomarker of successful aging, we have previously shown this worsens cognitive performance in the APP/PS1 mouse model of Alzheimer's disease (AD). We hypothesized that elevating Tc with thermotherapy would improve metabolism and cognition in APP/PS1 mice. From 6-12 months of age, male and female APP/PS1 and C57BL/6 mice were chronically housed at 23 or 30°C. At 12 months of age, mice were assayed for insulin sensitivity, glucose tolerance, and spatial cognition. Plasma, hippocampal, and peripheral (adipose, hepatic, and skeletal muscle) samples were procured postmortem and tissue-specific markers of amyloid accumulation, metabolism, and inflammation were assayed. Chronic 30°C exposure increased Tc in all groups except female APP/PS1 mice. All mice receiving thermotherapy had either improved glucose tolerance or insulin sensitivity, but the underlying processes responsible for these effects varied across sexes. In males, glucose regulation was influenced predominantly by hormonal signaling in plasma and skeletal muscle glucose transporter 4 expression, whereas in females, this was modulated at the tissue level. Thermotherapy improved spatial navigation in male C57BL/6 and APP/PS1 mice, with the later attributed to reduced hippocampal soluble amyloid-β (Aβ)42. Female APP/PS1 mice exhibited worse spatial memory recall after chronic thermotherapy. Together, the data highlights the metabolic benefits of passive thermotherapy, but future studies are needed to determine therapeutic benefits for those with AD.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"13237-13251"},"PeriodicalIF":3.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Addressing frailty in older adults: an integrated challenge for health, science, and society. 应对老年人虚弱：对健康、科学和社会的综合挑战。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-11-27 DOI: 10.18632/aging.206162

Samuel Fernández-Carnero, Oliver Martínez-Pozas, Juan Nicolás Cuenca-Zaldívar, Eleuterio A Sánchez-Romero

{"title":"Addressing frailty in older adults: an integrated challenge for health, science, and society.","authors":"Samuel Fernández-Carnero, Oliver Martínez-Pozas, Juan Nicolás Cuenca-Zaldívar, Eleuterio A Sánchez-Romero","doi":"10.18632/aging.206162","DOIUrl":"10.18632/aging.206162","url":null,"abstract":"Introduction: The global shift towards an aging population presents significant challenges, particularly concerning frailty among older adults. Frailty, characterized by diminished strength and resilience, increases vulnerability to diseases and hospitalization. Health Issues: Traditional diagnostic tools for frailty are costly and involve radiation risks, necessitating non-invasive, cost-effective methods like ultrasound. Frail older adults require intensive medical care, increasing healthcare costs and burdening systems. Scientific Challenges: Research must adopt a multidimensional approach, considering physical, psychological, and social factors of frailty. There is a pressing need to develop accessible diagnostic tools and translate research findings into clinical practice. Integrating ultrasound with machine learning enhances diagnostic accuracy and predictive capabilities, facilitating personalized care.Social implications: Frailty reduces the quality of life for older adults, places emotional and financial burdens on families, and exacerbates health inequalities. It also leads to social isolation, diminishing the participation of older adults in community activities.Future directions: An integrated response involving public health policies, technological innovations, and education is necessary. Developing community health programs, implementing continuous health monitoring tools, and conducting awareness campaigns can significantly improve frailty management.Conclusions: Tackling frailty is not only a health imperative but also a social and ethical responsibility. By addressing the intertwined health, scientific, and social challenges of frailty, we can ensure healthy and equitable aging for all, reflecting our commitment to improving the quality of life for older adults.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"16 ","pages":"13176-13180"},"PeriodicalIF":3.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurocognitive disparities: investigating ethnicity and mental health in rural aging adults. 神经认知差异：调查农村老年人的种族和心理健康。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-11-27 DOI: 10.18632/aging.206166

Carol Fadalla, Jonathan Singer, Peter Rerick, Lauren Elliott, Elisabeth McLean, Sydnie Schneider, Lauren Chrzanowski, Veronica Molinar-Lopez, Volker Neugebauer

{"title":"Neurocognitive disparities: investigating ethnicity and mental health in rural aging adults.","authors":"Carol Fadalla, Jonathan Singer, Peter Rerick, Lauren Elliott, Elisabeth McLean, Sydnie Schneider, Lauren Chrzanowski, Veronica Molinar-Lopez, Volker Neugebauer","doi":"10.18632/aging.206166","DOIUrl":"10.18632/aging.206166","url":null,"abstract":"Objectives: We explored whether depression and anxiety moderated the association of ethnicity and neurocognitive functioning among a sample of Hispanic and non-Hispanic White rural aging adults.Method: 1,462 rural dwelling adults (Mage = 59.4 years, SDage = 12.12) were included in the analysis for this study.Results: MANCOVAs revealed a significant (ps < .001) multivariate effect of ethnicity on all five indices of neurocognitive functioning when controlling for anxiety and sociodemographic variables (V = .20, F(5,1,310) = 64.69) and depression and sociodemographic variables in the second model (V = .20, F(5,1310) = 65.80, p < .001). There was also a multivariate effect of anxiety (V = .02, F(5,1310) = 4.57, p < .001) and depression (V = .04, F(5, 1310) = 11.38, p < .001) on neurocognitive functioning when controlling for sociodemographic variables and ethnicity.Conclusion: Findings revealed that Hispanic rural aging adults scored lower on neurocognitive functioning compared to non-Hispanic White rural aging adults, irrespective of depression or anxiety. Depression and anxiety contributed to lower scores on neurocognitive functioning-yet this finding was not as robust. Culturally tailored interventions targeting risk factors for neurocognitive impairment in Hispanic rural aging adults are imperative to mitigate neurocognitive disparities. One possible reason for differences in neurocognitive functioning between Hispanic individuals and non-Hispanic individuals is stress as ethnic health disparities have been found to be shaped by a diverse range of lifetime stressors that are disproportionally exacerbated for ethnic minorities.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"33-50"},"PeriodicalIF":3.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810062/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Supplementation with nicotinamide limits accelerated aging in affected individuals with cockayne syndrome and restores antioxidant defenses. 补充烟酰胺限制了科克因综合征患者的加速衰老，并恢复了抗氧化防御。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-11-26 DOI: 10.18632/aging.206160

Asma Chikhaoui, Kouloud Zayoud, Ichraf Kraoua, Sami Bouchoucha, Anis Tebourbi, Ilhem Turki, Houda Yacoub-Youssef

{"title":"Supplementation with nicotinamide limits accelerated aging in affected individuals with cockayne syndrome and restores antioxidant defenses.","authors":"Asma Chikhaoui, Kouloud Zayoud, Ichraf Kraoua, Sami Bouchoucha, Anis Tebourbi, Ilhem Turki, Houda Yacoub-Youssef","doi":"10.18632/aging.206160","DOIUrl":"10.18632/aging.206160","url":null,"abstract":"Cockayne syndrome (CS) is a segmental progeroid syndrome characterized by defects in the DNA excision repair pathway, predisposing to neurodegenerative manifestations. It is a rare genetic disorder and an interesting model for studying premature aging. Oxidative stress and autophagy play an important role in the aging process. The study of these two processes in a model of accelerated aging and the means to counteract them would lead to the identification of relevant biomarkers with therapeutic value for healthy aging. Here we investigated the gene expression profiles of several oxidative stress-related transcripts derived from CS-affected individuals and healthy elderly donors. We also explored the effect of nicotinamide supplementation on several genes related to inflammation and autophagy. Gene expression analysis revealed alterations in two main pathways. This involves the activation of arachidonic acid metabolism and the repression of the NRF2 pathway in affected individuals with CS. The supplementation with nicotinamide adjusted these abnormalities by enhancing autophagy and decreasing inflammation. Furthermore, CSA/CSB-dependent depletion of the mitochondrial DNA polymerase-γ catalytic subunit (POLG1) was restored following nicotinamide supplementation in CS-affected individuals' fibroblasts. This study reveals the link between oxidative stress and accelerated aging in affected individuals with CS and highlights new biomarkers of cellular senescence. However, further analyses are needed to confirm these results, which could not be carried out, mainly due to the unavailability of crucial samples of this rare disease.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"16 ","pages":"13271-13287"},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

When do the pathological signs become evident? Study of human mesenchymal stem cells in MDPL syndrome. 什么时候出现明显的病理症状？人间充质干细胞在MDPL综合征中的研究。

IF 3.9 3区医学

Aging-Us Pub Date : 2024-11-26 DOI: 10.18632/aging.206159

Spitalieri Paola, Guerrieri Lara, Murdocca Michela, Di Cesare Silvia, Maccaroni Serena, Pecorari Rosalba, Nardone Anna Maria, Candi Eleonora, Colasuonno Fiorella, Gori Giulia, Traficante Giovanna, Novelli Giuseppe, Sangiuolo Federica

{"title":"When do the pathological signs become evident? Study of human mesenchymal stem cells in MDPL syndrome.","authors":"Spitalieri Paola, Guerrieri Lara, Murdocca Michela, Di Cesare Silvia, Maccaroni Serena, Pecorari Rosalba, Nardone Anna Maria, Candi Eleonora, Colasuonno Fiorella, Gori Giulia, Traficante Giovanna, Novelli Giuseppe, Sangiuolo Federica","doi":"10.18632/aging.206159","DOIUrl":"10.18632/aging.206159","url":null,"abstract":"Aging syndromes are rare genetic disorders sharing the features of accelerated senescence. Among these, Mandibular hypoplasia, Deafness and Progeroid features with concomitant Lipodystrophy (MDPL; OMIM #615381) is a rare autosomal dominant disease due to a de novo in-frame deletion in POLD1 gene, encoding the catalytic subunit of DNA polymerase delta. Here, we investigated how MSCs may contribute to the phenotypes and progression of premature aging syndromes such as MDPL. In human induced pluripotent stem cells (hiPSCs)-derived MSCs of three MDPL patients we detected several hallmarks of senescence, including (i) abnormal nuclear morphology, (ii) micronuclei presence, (iii) slow cell proliferation and cell cycle progression, (iv) reduced telomere length, and (v) increased levels of mitochondrial reactive oxygen species (ROS). We newly demonstrated that the pathological hallmarks of senescence manifest at an early stage of human development and represent a warning sign for the progression of the disease. Dissecting the mechanisms underlying stem cell dysfunction during aging can thereby contribute to the development of timely pharmacological therapies for ameliorating the pathological phenotype.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"13505-13525"},"PeriodicalIF":3.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11723661/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0