Huntington's disease (HD) is an inherited neurodegenerative disease. 3-Nitropropionic acid (3-NP) causes increased reactive oxygen species production and neuroinflammation. Centella asiatica (CA) is a strong antioxidant. The aim of this study is to investigate the effect of hydroalcoholic extract of C. asiatica (HA-CA) on 3-NP-induced HD in adult zebrafish. Adult zebrafish (∼5-6 months old) weighing 470 to 530 mg was used and treated with 3-NP (5 mg/kg intraperitoneal [i.p.]). The animals received HA-CA (80 and 100 mg/L) daily for up to 28 days in water. Tetrabenazine (3 mg/kg i.p.) was used as a standard drug. We have done an open field test (for locomotor activity), a novel tank diving test (for anxiety), and a light and dark tank test (for memory), followed by biochemical analysis (acetyl-cholinesterase [AchEs], nitrite, lipid peroxidation [LPO], and glutathione [GSH]) and histopathology to further confirm memory dysfunctions. 3-NP-treated zebrafish exhibit reductions in body weight, progressive neuronal damage, cognition, and locomotor activity. The HA-CA group significantly reduced the 3-NP-induced increase in LPO, AchEs, and nitrite levels while decreasing GSH levels. Oral administration of HA-CA (80 or 100 mg/L) significantly reduces 3-NP-induced changes in body weight and behaviors, in addition to neuroinflammation in the brain by lowering tumor necrosis factor-α and interleukin-1β levels. Moreover, HA-CA significantly decreases the 3-NP-induced neuronal damage in the brain. HA-CA ameliorates neurotoxicity and neurobehavioral deficits in 3-NP-induced HD-like symptoms in adult zebrafish.
{"title":"Neuroprotective Potential of Hydroalcoholic Extract of <i>Centella asiatica</i> Against 3-Nitropropionic Acid-Induced Huntington's Like Symptoms in Adult Zebrafish.","authors":"Vishal Kumar, Charan Singh, Arti Singh","doi":"10.1089/rej.2022.0036","DOIUrl":"https://doi.org/10.1089/rej.2022.0036","url":null,"abstract":"<p><p>Huntington's disease (HD) is an inherited neurodegenerative disease. 3-Nitropropionic acid (3-NP) causes increased reactive oxygen species production and neuroinflammation. <i>Centella asiatica</i> (CA) is a strong antioxidant. The aim of this study is to investigate the effect of hydroalcoholic extract of <i>C. asiatica</i> (HA-CA) on 3-NP-induced HD in adult zebrafish. Adult zebrafish (∼5-6 months old) weighing 470 to 530 mg was used and treated with 3-NP (5 mg/kg intraperitoneal [<i>i.p.</i>]). The animals received HA-CA (80 and 100 mg/L) daily for up to 28 days in water. Tetrabenazine (3 mg/kg <i>i.p.</i>) was used as a standard drug. We have done an open field test (for locomotor activity), a novel tank diving test (for anxiety), and a light and dark tank test (for memory), followed by biochemical analysis (acetyl-cholinesterase [AchEs], nitrite, lipid peroxidation [LPO], and glutathione [GSH]) and histopathology to further confirm memory dysfunctions. 3-NP-treated zebrafish exhibit reductions in body weight, progressive neuronal damage, cognition, and locomotor activity. The HA-CA group significantly reduced the 3-NP-induced increase in LPO, AchEs, and nitrite levels while decreasing GSH levels. Oral administration of HA-CA (80 or 100 mg/L) significantly reduces 3-NP-induced changes in body weight and behaviors, in addition to neuroinflammation in the brain by lowering tumor necrosis factor-α and interleukin-1β levels. Moreover, HA-CA significantly decreases the 3-NP-induced neuronal damage in the brain. HA-CA ameliorates neurotoxicity and neurobehavioral deficits in 3-NP-induced HD-like symptoms in adult zebrafish.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 6","pages":"260-274"},"PeriodicalIF":2.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10342037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-01Epub Date: 2022-10-12DOI: 10.1089/rej.2022.0009
Jing Tian, Ze Li, Yuanyuan Jiang, Wenjin Gu, Enqi Kong, Quan Hao, Beihua Kong, Li Sun
Cisplatin is widely used in chemotherapies in cervical cancer (CC). Nevertheless, drug resistance in cancer patients poses a major threat to efficacy of treatment. To explore the underlying modulatory mechanism of SOX21-AS1 in cisplatin resistance in CC cell and mice models, Gepia database was referred for SOX21-AS1 expression in cancer tissues and normal ones. Reverse transcription quantitative real-time polymerase chain reaction was used to measure the differential expression of SOX21-AS1 in parental Siha cells and cisplatin-resistant Siha/DDP cells. Luciferase reporter gene assays were conducted to verify putative bindings between SOX21-AS1 and miR-9-3p. Western blot method was employed to evaluate the changes in cleaved-caspase 7 protein expression. Cisplatin resistance was evaluated in each transfected group using cell counting kit 8 method after cells were exposed to cisplatin (0, 7.5, 15, 30, 60, 120, and 240 μg/mL) for 24 hours. Flow cytometry method was used to measure the apoptosis rates. Cell migration and invasion were measured using Transwell assays. Immunofluorescence method was applied to observe epithelial to mesenchymal transition (EMT) markers, including E-cadherin, Snail, matrix metalloproteinase (MMP)3, and MMP9. Siha/DDP cell groups stably transfected with sh-NC and sh-SOX21-AS1 were injected through tail vein of Balb/C mice. Lung tissue sections were used for hematoxylin and eosin staining and immunohistochemistry analysis. SOX1-AS1 expression was higher in cancer tissues than normal ones and was also higher in Siha/DDP rather than Siha cells. SOX21-AS1 was targeted by miR-9-3p in CC cells. Downregulation of SOX21-AS1 or overexpression of miR-9-3p inhibited cisplatin resistance in Siha/DDP cells and reduced cell invasion and migration and attenuated EMT progression. In vivo, the SOX21-AS1 knockdown led to less severe lung metastasis. Downregulation of SOX21-AS1 alleviated cisplatin resistance in CC through EMT inhibition.
{"title":"Downregulation of <i>SOX21-AS1</i> Alleviated Cisplatin Resistance in Cervical Cancer Through Epithelial-Mesenchymal Transition Inhibition.","authors":"Jing Tian, Ze Li, Yuanyuan Jiang, Wenjin Gu, Enqi Kong, Quan Hao, Beihua Kong, Li Sun","doi":"10.1089/rej.2022.0009","DOIUrl":"https://doi.org/10.1089/rej.2022.0009","url":null,"abstract":"<p><p>Cisplatin is widely used in chemotherapies in cervical cancer (CC). Nevertheless, drug resistance in cancer patients poses a major threat to efficacy of treatment. To explore the underlying modulatory mechanism of <i>SOX21-AS1</i> in cisplatin resistance in CC cell and mice models, Gepia database was referred for <i>SOX21-AS1</i> expression in cancer tissues and normal ones. Reverse transcription quantitative real-time polymerase chain reaction was used to measure the differential expression of <i>SOX21-AS1</i> in parental Siha cells and cisplatin-resistant Siha/DDP cells. Luciferase reporter gene assays were conducted to verify putative bindings between <i>SOX21-AS1</i> and <i>miR-9-3p</i>. Western blot method was employed to evaluate the changes in cleaved-caspase 7 protein expression. Cisplatin resistance was evaluated in each transfected group using cell counting kit 8 method after cells were exposed to cisplatin (0, 7.5, 15, 30, 60, 120, and 240 μg/mL) for 24 hours. Flow cytometry method was used to measure the apoptosis rates. Cell migration and invasion were measured using Transwell assays. Immunofluorescence method was applied to observe epithelial to mesenchymal transition (EMT) markers, including E-cadherin, Snail, matrix metalloproteinase (MMP)3, and MMP9. Siha/DDP cell groups stably transfected with sh-NC and sh-<i>SOX21-AS1</i> were injected through tail vein of Balb/C mice. Lung tissue sections were used for hematoxylin and eosin staining and immunohistochemistry analysis. <i>SOX1-AS1</i> expression was higher in cancer tissues than normal ones and was also higher in Siha/DDP rather than Siha cells. <i>SOX21-AS1</i> was targeted by <i>miR-9-3p</i> in CC cells. Downregulation of <i>SOX21-AS1</i> or overexpression of <i>miR-9-3p</i> inhibited cisplatin resistance in Siha/DDP cells and reduced cell invasion and migration and attenuated EMT progression. <i>In vivo</i>, the <i>SOX21-AS1</i> knockdown led to less severe lung metastasis. Downregulation of <i>SOX21-AS1</i> alleviated cisplatin resistance in CC through EMT inhibition.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 5","pages":"243-252"},"PeriodicalIF":2.6,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33446910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Pan, Zhenzhen Gu, Yansi Lyu, Yi Yang, Man-Hon Chung, Xiaohua Pan, S. Cai
Senescence is a form of durable cell cycle arrest elicited in response to a wide range of stimuli. Senescent cells remain metabolically active and secrete a variety of factors collectively termed senescence-associated secretory phenotype (SASP). SASP is highly pleiotropic and can impact numerous biological processes in which it has both beneficial and deleterious roles. The underlying mechanisms by which SASP exerts its pleiotropic influence remain largely unknown. SASP serves as an environmental factor, which regulates stem cell differentiation and alters its routine. The latter can potentially be accomplished through dedifferentiation, transdifferentiation, or reprogramming. Behavioral changes that cells undergo when exposed to SASP are involved in several senescence-associated physiological and pathological phenomena. These findings provide clues for identifying possible interventions to reduce the deleterious effects without interfering in the beneficial outcomes. Here, we discuss the multifaced effects of SASP and the changes occurring in cellular states upon exposure to SASP factors.
{"title":"Link between senescence and cell fate: Senescence-associated secretory phenotype (SASP) and its effects on stem cell fate transition.","authors":"Y. Pan, Zhenzhen Gu, Yansi Lyu, Yi Yang, Man-Hon Chung, Xiaohua Pan, S. Cai","doi":"10.1089/rej.2022.0021","DOIUrl":"https://doi.org/10.1089/rej.2022.0021","url":null,"abstract":"Senescence is a form of durable cell cycle arrest elicited in response to a wide range of stimuli. Senescent cells remain metabolically active and secrete a variety of factors collectively termed senescence-associated secretory phenotype (SASP). SASP is highly pleiotropic and can impact numerous biological processes in which it has both beneficial and deleterious roles. The underlying mechanisms by which SASP exerts its pleiotropic influence remain largely unknown. SASP serves as an environmental factor, which regulates stem cell differentiation and alters its routine. The latter can potentially be accomplished through dedifferentiation, transdifferentiation, or reprogramming. Behavioral changes that cells undergo when exposed to SASP are involved in several senescence-associated physiological and pathological phenomena. These findings provide clues for identifying possible interventions to reduce the deleterious effects without interfering in the beneficial outcomes. Here, we discuss the multifaced effects of SASP and the changes occurring in cellular states upon exposure to SASP factors.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42060215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Duozhuang Tang, Jianying Wu, Yiting Wang, Hui Cui, Zhendong Tao, Lang Lei, Zhuangfa Zhou, Si Tao
Ultraviolet B (UVB) radiation may influence the occurrence or even worsen cutaneous disorders from inflammatory to neoplastic disorders. Dietary restriction (DR) is a well-known regimen that can retard aging-associated pathologies, and is shown by us and others that it can significantly inhibit inflammation under various conditions, including in both undisturbed and stressed settings. It is unknown whether DR could act as a nonpharmacological factor to protect skin against UVB-induced damage. In this study, we performed 30% DR to mice 1 week before UVB irradiation (798.6 mJ/cm2). Remarkably, continuous DR significantly ameliorated UVB-induced skin damage and histological changes, associated with a great reduction in the inflammatory responses in the skin. Intriguingly, refed DR mice with ad libitum diet even 24 hours postirradiation reinflamed the inflammatory responses and induced significantly strong damage to the skin. Together, this study provides the first experimental evidence that DR greatly protects mouse skin from high dose of UVB irradiation, which if translatable could have great implications in human beings.
紫外线B (UVB)辐射可以影响皮肤疾病的发生，甚至加重皮肤疾病，从炎症性疾病到肿瘤性疾病。饮食限制(DR)是一种众所周知的疗法，可以延缓衰老相关的病理，我们和其他人都表明，它可以在各种情况下显著抑制炎症，包括在未受干扰和有压力的情况下。目前尚不清楚DR是否可以作为一种非药物因素来保护皮肤免受uvb引起的损伤。在这项研究中，我们在UVB照射前1周对小鼠进行30% DR (798.6 mJ/cm2)。值得注意的是，持续DR显著改善了uvb诱导的皮肤损伤和组织学变化，并显著减少了皮肤炎症反应。有趣的是，即使在放疗后24小时，随意饮食的DR小鼠也会再次引起炎症反应，并对皮肤造成明显的强烈损伤。总之，这项研究提供了第一个实验证据，证明DR可以有效地保护小鼠皮肤免受高剂量UVB辐射，如果可以转化为对人类有很大的影响。
{"title":"Dietary Restriction Attenuates Inflammation and Protects Mouse Skin from High-Dose Ultraviolet B Irradiation.","authors":"Duozhuang Tang, Jianying Wu, Yiting Wang, Hui Cui, Zhendong Tao, Lang Lei, Zhuangfa Zhou, Si Tao","doi":"10.1089/rej.2021.0022","DOIUrl":"https://doi.org/10.1089/rej.2021.0022","url":null,"abstract":"<p><p>Ultraviolet B (UVB) radiation may influence the occurrence or even worsen cutaneous disorders from inflammatory to neoplastic disorders. Dietary restriction (DR) is a well-known regimen that can retard aging-associated pathologies, and is shown by us and others that it can significantly inhibit inflammation under various conditions, including in both undisturbed and stressed settings. It is unknown whether DR could act as a nonpharmacological factor to protect skin against UVB-induced damage. In this study, we performed 30% DR to mice 1 week before UVB irradiation (798.6 mJ/cm<sup>2</sup>). Remarkably, continuous DR significantly ameliorated UVB-induced skin damage and histological changes, associated with a great reduction in the inflammatory responses in the skin. Intriguingly, refed DR mice with <i>ad libitum</i> diet even 24 hours postirradiation reinflamed the inflammatory responses and induced significantly strong damage to the skin. Together, this study provides the first experimental evidence that DR greatly protects mouse skin from high dose of UVB irradiation, which if translatable could have great implications in human beings.</p>","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"25 3","pages":"149-157"},"PeriodicalIF":2.6,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247678/pdf/rej.2021.0022.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9555196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. S. Silva Neto, C. D. Dos Santos, Andrea Travassos, A. Figueiredo, D. P. Nunes, T. Rosa, Fabrício Cavalcante Frauzino, Wesquisley Vidal de Santana, L. F. Sesti, Genildo Ferreira Nunes, Emerson Moura Ribeiro, N. B. Osório
BACKGROUND Muscle weakness is associated with negative outcomes, in addition to being related to the pathogenesis of frailty and functional disability in the older individuals. Muscle strength and functionality are considered biomarkers of aging. Progressive resistance training (PRT) is a type of training that has been the subject of studies as it presents itself as a therapeutic option to fight the reduction of muscle strength and functionality in older individuals. However, few studies have assessed the clinically-relevant gains in the levels of muscle strength and functionality of older individuals after PRT, in addition to the need of testing new PRT approaches, including individualization and periodization in training programs. Therefore, this article aims to assess the effect of a individual and periodized PRT protocol on handgrip strength and functionality in older individuals. Thus, the study sample included 69 older individuals, divided into two groups: case (n = 41) and control (n = 28). The case group participated in a progressive resistance training protocol for 12 weeks, with two weekly sessions. When compared to the control group, which received only health education, the individuals in the case group had a greater magnitude of improvement in all variables related to the assessed functionality (Timed up and go test, gait speed, and handgrip strength), proving the applicability of the assessed protocol to improve strength and functionality in the older individuals people of a community.
{"title":"THE EFFECT OF PROGRESSIVE RESISTANCE TRAINING ON FUNCTIONALITY AND HANDGRIP STRENGTH IN THE OLDER INDIVIDUALS OF A COMMUNITY: A QUASI-EXPERIMENTAL STUDY.","authors":"L. S. Silva Neto, C. D. Dos Santos, Andrea Travassos, A. Figueiredo, D. P. Nunes, T. Rosa, Fabrício Cavalcante Frauzino, Wesquisley Vidal de Santana, L. F. Sesti, Genildo Ferreira Nunes, Emerson Moura Ribeiro, N. B. Osório","doi":"10.1089/rej.2021.0029","DOIUrl":"https://doi.org/10.1089/rej.2021.0029","url":null,"abstract":"BACKGROUND\u0000Muscle weakness is associated with negative outcomes, in addition to being related to the pathogenesis of frailty and functional disability in the older individuals. Muscle strength and functionality are considered biomarkers of aging. Progressive resistance training (PRT) is a type of training that has been the subject of studies as it presents itself as a therapeutic option to fight the reduction of muscle strength and functionality in older individuals. However, few studies have assessed the clinically-relevant gains in the levels of muscle strength and functionality of older individuals after PRT, in addition to the need of testing new PRT approaches, including individualization and periodization in training programs. Therefore, this article aims to assess the effect of a individual and periodized PRT protocol on handgrip strength and functionality in older individuals. Thus, the study sample included 69 older individuals, divided into two groups: case (n = 41) and control (n = 28). The case group participated in a progressive resistance training protocol for 12 weeks, with two weekly sessions. When compared to the control group, which received only health education, the individuals in the case group had a greater magnitude of improvement in all variables related to the assessed functionality (Timed up and go test, gait speed, and handgrip strength), proving the applicability of the assessed protocol to improve strength and functionality in the older individuals people of a community.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42881698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ana Fernández-Araque, Laura García-de-Diego, María Martínez-Ferrán, I. Diez-Vega, T. Yvert, T. Mingo, C. Santiago, H. Pareja-Galeano, Z. Verde
Hospitalization in older population leads to a decline in physical function, physical condition and independency. However, a scarce number of studies has addressed the effect of being in good physical condition on the risk of hospitalization and polypharmacy in older people. Therefore, this study aims to examine the relationship between physical condition and other health factors, and the incidence of hospitalization and polypharmacy in Spanish older persons. For this cross-sectional study 102 community-dwelling persons aged 80 years or older who were being treated at three primary care centers. The data collected were number of hospitalizations and medications, dietary habits, nutrition status, quality of life, independence in activities of daily life, physical performance and associated genotype data. Scoring higher in the tests Chair stand and 8-Foot Up-and-go was found associated with reduced risks of hospitalization [OR = .45 (95% CI = .2, .99); OR .32 (95% CI = .12, .86)] and polypharmacy [OR = .36 (95% CI = .16, .8); OR= .28 (95% CI = .1, .78)]. The number of medications was also lower in individuals with a greater aerobic capacity and activities of daily life independence [OR = .28 (95% CI = .1, .78); OR = .37 (95% CI = .16, .82)]. No associations were found with the remaining physical performance tests or other factors assessed. Our findings point to benefits of greater strength, balance and aerobic capacity in terms of reducing the risk of hospitalization and polypharmacy.
{"title":"Physical Condition and Risk of Hospitalization and Polypharmacy in Older Adults.","authors":"Ana Fernández-Araque, Laura García-de-Diego, María Martínez-Ferrán, I. Diez-Vega, T. Yvert, T. Mingo, C. Santiago, H. Pareja-Galeano, Z. Verde","doi":"10.1089/rej.2021.0030","DOIUrl":"https://doi.org/10.1089/rej.2021.0030","url":null,"abstract":"Hospitalization in older population leads to a decline in physical function, physical condition and independency. However, a scarce number of studies has addressed the effect of being in good physical condition on the risk of hospitalization and polypharmacy in older people. Therefore, this study aims to examine the relationship between physical condition and other health factors, and the incidence of hospitalization and polypharmacy in Spanish older persons. For this cross-sectional study 102 community-dwelling persons aged 80 years or older who were being treated at three primary care centers. The data collected were number of hospitalizations and medications, dietary habits, nutrition status, quality of life, independence in activities of daily life, physical performance and associated genotype data. Scoring higher in the tests Chair stand and 8-Foot Up-and-go was found associated with reduced risks of hospitalization [OR = .45 (95% CI = .2, .99); OR .32 (95% CI = .12, .86)] and polypharmacy [OR = .36 (95% CI = .16, .8); OR= .28 (95% CI = .1, .78)]. The number of medications was also lower in individuals with a greater aerobic capacity and activities of daily life independence [OR = .28 (95% CI = .1, .78); OR = .37 (95% CI = .16, .82)]. No associations were found with the remaining physical performance tests or other factors assessed. Our findings point to benefits of greater strength, balance and aerobic capacity in terms of reducing the risk of hospitalization and polypharmacy.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48184097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We aimed to investigate the association of circulatory senescence-associated secretory phenotypes (SASP) produced by senescent cells with chronological and menopausal age in women aged 45 years or more. The proteomic profiles for 32 SASP factors of plasma samples were measured in 76 healthy postmenopausal women aged 46-82 years from the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study (KoGES-CAVAS). We assessed the association between the SASP factors and aging indicators (chronological age, menopausal age, and years since menopause) using single- and multi-protein models. First, we composed a profile of proteins associated with chronological age, menopausal age, and years since menopause. In a single-protein model, three proteins (growth differentiation factor 15 (GDF15), insulin-like growth factor binding protein-2 (IGFBP-2), and tumor necrosis factor-α (TNF-α)) are positively associated with chronological age. Menopausal age and years since menopause are interrelated with Interlukin-8 (IL-8). The direction of association between menopausal age and monocyte chemoattractant protein-1 (MCP-1) was only negative, and IGFBP-2 and TNF-α were significant in all three aging factors. We also constructed parsimonious multi-protein models to confirm the association of the proteomic signature for aging after adjusting for covariates and the combination of proteomic signature of 13 proteins (GDF15, IFN-γ, IGFBP-2, IGFBP-7, IL-15, IL-1β, IL-17A, IL-8, MCP-1, TIMP-2, TNF-α, VEGF-A, and IP-10) appear to be associated with chronological age and menopausal state of individuals. Thus, by observing association between the selected SASPs and age-related markers among healthy postmenopausal women, we examine how menopause in women relates to proteomic indicators of aging and highlight the potential use of SASP factors as a marker to reflect the state of biological aging attributed by ovarian senescence.
{"title":"Plasma proteomic signature of cellular senescence and markers of biological aging among postmenopausal women.","authors":"Ji-Won Shin, Eunil Lee, Seungbong Han, Seungyong Choi, Ok-hee Jeon","doi":"10.1089/rej.2022.0024","DOIUrl":"https://doi.org/10.1089/rej.2022.0024","url":null,"abstract":"We aimed to investigate the association of circulatory senescence-associated secretory phenotypes (SASP) produced by senescent cells with chronological and menopausal age in women aged 45 years or more. The proteomic profiles for 32 SASP factors of plasma samples were measured in 76 healthy postmenopausal women aged 46-82 years from the Korean Genome and Epidemiology Study Cardiovascular Disease Association Study (KoGES-CAVAS). We assessed the association between the SASP factors and aging indicators (chronological age, menopausal age, and years since menopause) using single- and multi-protein models. First, we composed a profile of proteins associated with chronological age, menopausal age, and years since menopause. In a single-protein model, three proteins (growth differentiation factor 15 (GDF15), insulin-like growth factor binding protein-2 (IGFBP-2), and tumor necrosis factor-α (TNF-α)) are positively associated with chronological age. Menopausal age and years since menopause are interrelated with Interlukin-8 (IL-8). The direction of association between menopausal age and monocyte chemoattractant protein-1 (MCP-1) was only negative, and IGFBP-2 and TNF-α were significant in all three aging factors. We also constructed parsimonious multi-protein models to confirm the association of the proteomic signature for aging after adjusting for covariates and the combination of proteomic signature of 13 proteins (GDF15, IFN-γ, IGFBP-2, IGFBP-7, IL-15, IL-1β, IL-17A, IL-8, MCP-1, TIMP-2, TNF-α, VEGF-A, and IP-10) appear to be associated with chronological age and menopausal state of individuals. Thus, by observing association between the selected SASPs and age-related markers among healthy postmenopausal women, we examine how menopause in women relates to proteomic indicators of aging and highlight the potential use of SASP factors as a marker to reflect the state of biological aging attributed by ovarian senescence.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48415447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Trevisan, Francesca Remelli, S. Fumagalli, E. Mossello, C. Okoye, G. Bellelli, A. Coin, A. Malara, P. Gareri, F. Monzani, S. Del Signore, G. Zia, R. Antonelli Incalzi, S. Volpato
Covid-19 may have a heterogeneous onset, especially in older age. However, whether and how Covid-19 signs and symptoms may present and aggregate together according to sociodemographic and health factors is unclear, as well as their prognostic value. This work included 981 Covid-19 inpatients who participated in the GeroCovid Observational study. Signs/symptoms at disease onset, sociodemographic, health, cognitive status, and mobility were systematically recorded. Clusters of signs/symptoms were identified through agglomerative hierarchical clustering. The associations of single signs/symptoms and symptom clusters with longer hospitalization (≥16 days) and in-hospital mortality were explored through logistic and Cox regressions. The signs/symptoms most reported in our sample (age 78.3±9.39 years; 49.4% women) were fever (62.5%), cough (45.5%), and dyspnoea (62.7%). Atypical were reported by up to one-third of patients, and delirium by 9.1%. Atypical symptoms were more frequent with advancing age and with lower pre-Covid-19 cognitive and mobility levels. Older men more likely reported respiratory symptoms than women. Dyspnoea (HR=1.47, 95%CI:1.02-2.12), tachypnea (HR=1.53, 95%CI:1.14-2.07), low oxygen saturation (HR=1.95, 95%CI:1.32-2.88) and delirium (HR=1.60, 95%CI:1.13-2.28) were associated with higher in-hospital mortality. Four symptom clusters were identified. Compared with the mild respiratory symptoms cluster, the severe clinical impairment cluster was associated with higher mortality (HR=2.57, 95%CI:1.58-4.18). The severe clinical impairment and aspecific symptoms clusters were associated with longer hospitalization (OR=2.38, 95%CI:1.56-3.63, and OR=1.75, 95%CI:1.08-2.83, respectively). Multiple health aspects influence Covid-19 clinical presentation. A symptom clusters approach may help predict adverse health outcomes in older patients. In addition to respiratory symptoms, delirium is independently associated with mortality risk.
{"title":"Covid-19 as a paradigmatic model of the heterogeneous disease presentation in older people: data from the GeroCovid Observational study.","authors":"C. Trevisan, Francesca Remelli, S. Fumagalli, E. Mossello, C. Okoye, G. Bellelli, A. Coin, A. Malara, P. Gareri, F. Monzani, S. Del Signore, G. Zia, R. Antonelli Incalzi, S. Volpato","doi":"10.1089/rej.2021.0063","DOIUrl":"https://doi.org/10.1089/rej.2021.0063","url":null,"abstract":"Covid-19 may have a heterogeneous onset, especially in older age. However, whether and how Covid-19 signs and symptoms may present and aggregate together according to sociodemographic and health factors is unclear, as well as their prognostic value. This work included 981 Covid-19 inpatients who participated in the GeroCovid Observational study. Signs/symptoms at disease onset, sociodemographic, health, cognitive status, and mobility were systematically recorded. Clusters of signs/symptoms were identified through agglomerative hierarchical clustering. The associations of single signs/symptoms and symptom clusters with longer hospitalization (≥16 days) and in-hospital mortality were explored through logistic and Cox regressions. The signs/symptoms most reported in our sample (age 78.3±9.39 years; 49.4% women) were fever (62.5%), cough (45.5%), and dyspnoea (62.7%). Atypical were reported by up to one-third of patients, and delirium by 9.1%. Atypical symptoms were more frequent with advancing age and with lower pre-Covid-19 cognitive and mobility levels. Older men more likely reported respiratory symptoms than women. Dyspnoea (HR=1.47, 95%CI:1.02-2.12), tachypnea (HR=1.53, 95%CI:1.14-2.07), low oxygen saturation (HR=1.95, 95%CI:1.32-2.88) and delirium (HR=1.60, 95%CI:1.13-2.28) were associated with higher in-hospital mortality. Four symptom clusters were identified. Compared with the mild respiratory symptoms cluster, the severe clinical impairment cluster was associated with higher mortality (HR=2.57, 95%CI:1.58-4.18). The severe clinical impairment and aspecific symptoms clusters were associated with longer hospitalization (OR=2.38, 95%CI:1.56-3.63, and OR=1.75, 95%CI:1.08-2.83, respectively). Multiple health aspects influence Covid-19 clinical presentation. A symptom clusters approach may help predict adverse health outcomes in older patients. In addition to respiratory symptoms, delirium is independently associated with mortality risk.","PeriodicalId":20979,"journal":{"name":"Rejuvenation research","volume":"24 6","pages":""},"PeriodicalIF":2.6,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41248887","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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