The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

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The causal effect of adult height on late-life handgrip strength: The Singapore Chinese Health Study. 成人身高对晚年握力的因果效应:新加坡华人健康研究
Xuling Chang, Kevin Yiqiang Chua, Chih Chuan Shih, Jieqi Chen, Ai Shan Lee, Patrick Tan, Ling Wang, Jianjun Liu, Chew-Kiat Heng, Jian-Min Yuan, Chiea Chuen Khor, Rajkumar Dorajoo, Woon-Puay Koh
{"title":"The causal effect of adult height on late-life handgrip strength: The Singapore Chinese Health Study.","authors":"Xuling Chang, Kevin Yiqiang Chua, Chih Chuan Shih, Jieqi Chen, Ai Shan Lee, Patrick Tan, Ling Wang, Jianjun Liu, Chew-Kiat Heng, Jian-Min Yuan, Chiea Chuen Khor, Rajkumar Dorajoo, Woon-Puay Koh","doi":"10.1093/gerona/glae216","DOIUrl":"https://doi.org/10.1093/gerona/glae216","url":null,"abstract":"<p><strong>Background: </strong>Adult height has been associated with handgrip strength, which is a surrogate marker of physical frailty. However, it is uncertain if this association is causative or due to confounding bias.</p><p><strong>Methods: </strong>We evaluated pairwise associations among handgrip strength, adult height and genetically determined height [using a polygenic score (PGS) for height in a mediation framework and a two-sample Mendelian randomisation approach] by means of multivariable regression model using a prospective cohort of Chinese living in Singapore. We additionally evaluated pathway enrichments of height-related genes in relation to increased handgrip strength to discover common biological mechanisms underlying associations of genetically determined height with handgrip strength.</p><p><strong>Results: </strong>Height PGS exhibited a positive association with handgrip strength at late life after adjusting for midlife body weight and other baseline exposures (cigarette smoking, education and physical activity status, P=1.2×10-9). Approximately 66.4% of the total effect of height PGS on handgrip strength was mediated through adult height (βindirect-effect=0.034, Pindirect-effect=1.4×10-40). Two-sample Mendelian randomisation evaluations showed a consistent causal relationship between increased height and increased handgrip strength in late life (P between 6.6×10-4 and 3.9×10-18), with insignificant horizontal pleiotropic effects (PMR-Egger  intercept=0.853). Pathway analyses of genes related to both increased adult height and handgrip strength revealed enrichment in ossification and adipogenesis pathways (Padj between 0.034 to 6.8×10-4).</p><p><strong>Conclusions: </strong>The study highlights on a potentially causal effect between increased adult height and increased handgrip strength at late life, which may be explained by related biological processes underlying preservation of muscle mass and strength in ageing.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142083000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Network analysis of brain and bone tissue transcripts reveals shared molecular mechanisms underlying Alzheimer's Disease and related dementias (ADRD) and Osteoporosis. 对脑组织和骨组织转录本的网络分析揭示了阿尔茨海默病及相关痴呆症(ADRD)和骨质疏松症的共同分子机制。
Archana Nagarajan, Jason Laird, Obiadada Ugochukwu, Sjur Reppe, Kaare Gautvik, Ryan D Ross, David A Bennett, Clifford Rosen, Douglas P Kiel, Lenora A Higginbotham, Nicholas T Seyfried, Christine W Lary
{"title":"Network analysis of brain and bone tissue transcripts reveals shared molecular mechanisms underlying Alzheimer's Disease and related dementias (ADRD) and Osteoporosis.","authors":"Archana Nagarajan, Jason Laird, Obiadada Ugochukwu, Sjur Reppe, Kaare Gautvik, Ryan D Ross, David A Bennett, Clifford Rosen, Douglas P Kiel, Lenora A Higginbotham, Nicholas T Seyfried, Christine W Lary","doi":"10.1093/gerona/glae211","DOIUrl":"https://doi.org/10.1093/gerona/glae211","url":null,"abstract":"<p><p>Alzheimer's disease and related dementias (ADRD) and osteoporosis (OP) are two prevalent diseases of aging with demonstrated epidemiological association, but the underlying molecular mechanisms contributing to this association are unknown. We used network analysis of bone and brain transcriptomes to discover common molecular mechanisms underlying these two diseases. Our study included RNA-sequencing data from the dorsolateral prefrontal cortex tissue of autopsied brains in 629 participants from ROSMAP (Religious Orders Study and the Rush Memory and Aging Project), with a subgroup of 298 meeting criteria for inclusion in five ADRD categories, and RNA array data from transiliac bone biopsies in 84 participants from the Oslo study of postmenopausal women. After developing each network within each tissue, we analyzed associations between modules (groups of co-expressed genes) with multiple bone and neurological traits, examined overlap in modules between networks, and performed pathway enrichment analysis to discover conserved mechanisms. We discovered three modules in ROSMAP that showed significant associations with ADRD and bone related traits and four modules in Oslo that showed significant associations with multiple bone outcomes. We found significant module overlap between the two networks in modules linked to signaling, tissue homeostasis, and development, and Wingless-related integration site (Wnt) signaling was found to be highly enriched in OP and ADRD modules of interest. These results provide translational opportunities in the development of treatments and biomarkers for ADRD and OP.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lumican is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting VSMCs Senescence through Interacting with Integrin α2β1. Lumican 既是血管老化的新型危险因素,也是潜在的血浆生物标志物,它能通过与整合素 α2β1 相互作用促进血管内皮细胞衰老。
Mandi Luo, Dan Yan, Yi Huang, Tianyi Ji, Pengcheng Luo, Zhen Yang, Shangbang Gao, Le Zhang, Yiwu Zhou, Qing Shi, Yongping Bai, Tao Li, Lei Ruan, Cuntai Zhang
{"title":"Lumican is Both a Novel Risk Factor and Potential Plasma Biomarker for Vascular Aging, Capable of Promoting VSMCs Senescence through Interacting with Integrin α2β1.","authors":"Mandi Luo, Dan Yan, Yi Huang, Tianyi Ji, Pengcheng Luo, Zhen Yang, Shangbang Gao, Le Zhang, Yiwu Zhou, Qing Shi, Yongping Bai, Tao Li, Lei Ruan, Cuntai Zhang","doi":"10.1093/gerona/glae214","DOIUrl":"https://doi.org/10.1093/gerona/glae214","url":null,"abstract":"<p><p>Vascular aging, a common pathogenesis of senile chronic diseases, significantly increases morbidity and mortality in older adults; its intricate cellular and molecular mechanisms necessitate further investigation. Lumican (LUM) and integrin α2β1(ITGα2β1) are profibrotic extracellular matrix proteins and vital cell regulatory receptors, respectively. However, their roles in vascular aging remain unclear. This study sought to elucidate the connection between LUM and vascular aging as well as the biological mechanism of LUM/ITGα2β1 in this process. Using an enzyme-linked immunosorbent assay, we discovered that plasma LUM was elevated in vascular aging individuals and was positively correlated with brachial-ankle pulse wave velocity. Additionally, immunohistochemical and western blot analyses confirmed LUM upregulation in arteries of older adults and aged mice, as well as in senescent vascular smooth cells (VSMCs). Wild-type and LUM semiknockout (Lum-/+) mice, along with primary VSMCs extracted from these mice, were exposed to angiotensin II (Ang II) to induce stress-induced senescence model. LUM semiknockout mitigated Ang Ⅱ-induced arteriosclerosis, hypertension, vascular aging and remodeling in mice. Both in vitro and in vivo studies revealed that LUM deficiency suppressed p53, p21, collagen 1 and collagen 3 upregulation and synthetic phenotype formation in VSMCs stimulated by Ang Ⅱ. Treating VSMCs with a ITGα2β1 antagonist reversed the aforementioned changes triggered by LUM proteins. Briefly, LUM functions as a potential marker and risk factor for vascular aging and promotes pathological changes by affecting ITGα2β1 in VSMCs. This study introduces a novel molecular target for the early diagnosis and treatment of vascular aging and age-related vascular diseases.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging. 对比增强超声成像检测大鼠颈椎微血管随着正常衰老而发生的解剖和功能变化。
Jennifer N Harmon, Preeja Chandran, Abarajithan Chandrasekaran, Jeffrey E Hyde, Gustavo J Hernandez, May J Reed, Matthew F Bruce, Zin Z Khaing
{"title":"Contrast-enhanced ultrasound imaging detects anatomical and functional changes in rat cervical spine microvasculature with normal aging.","authors":"Jennifer N Harmon, Preeja Chandran, Abarajithan Chandrasekaran, Jeffrey E Hyde, Gustavo J Hernandez, May J Reed, Matthew F Bruce, Zin Z Khaing","doi":"10.1093/gerona/glae215","DOIUrl":"10.1093/gerona/glae215","url":null,"abstract":"<p><p>Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. While these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 mo., N=6) exhibited significant tortuosity in the anterior spinal artery and elevated vascular resistance compared to adults (4-6 mo., N=6; tortuosity index 2.20±0.15 vs 4.74±0.45, p<0.05). Baseline blood volume was lower in both larger vessels and the microcirculation in the aged cohort, specifically in white matter (4.44e14±1.37e13 vs 3.66e14±2.64e13 CEUS bolus AUC, p<0.05). To elucidate functional differences, animals were exposed to a hypoxia challenge; whereas adult rats exhibited significant functional hyperemia in both gray and white matter (GM: 1.13±0.10-fold change from normoxia, p<0.05; WM: 1.16±0.13, p<0.05), aged rats showed no response. Immunohistochemistry revealed reduced pericyte coverage and activated microglia behavior in aged rats, which may partially explain the lack of vascular response. This study provides the first in vivo description of age-related hemodynamic differences in the cervical spinal cord.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis. 抑制 OLR1 可通过靶向自噬-GATA4 轴减少髓核细胞的 SASP。
Jia-Wei Gao, Hang Shi, Fu-Ping Gao, Zhi-Min Zhou, Xin Peng, Rui Sun, V L F Cabral, Jian Li, Yun-Tao Wang, Xiao-Hu Wang, Xiao-Tao Wu
{"title":"Inhibition of OLR1 reduces SASP of nucleus pulposus cells by targeting autophagy-GATA4 axis.","authors":"Jia-Wei Gao, Hang Shi, Fu-Ping Gao, Zhi-Min Zhou, Xin Peng, Rui Sun, V L F Cabral, Jian Li, Yun-Tao Wang, Xiao-Hu Wang, Xiao-Tao Wu","doi":"10.1093/gerona/glae204","DOIUrl":"https://doi.org/10.1093/gerona/glae204","url":null,"abstract":"<p><p>Targeting cellular senescence and Senescence Associated Secretory Phenotype (SASP) through autophagy has emerged as a promising intervertebral disc (IVD) degeneration (IDD) treatment strategy in recent years. This study aimed to clarify the role and mechanism of autophagy in preventing IVD SASP. Methods involved in vitro experiments with nucleus pulposus (NP) tissues from normal and IDD patients, as well as an in vivo IDD animal model. GATA4's regulatory role in SASP was validated both in vitro and in vivo, while autophagy modulators were employed to assess their impact on GATA4 and SASP. Transcriptomic sequencing identified Oxidized low-density lipoprotein receptor 1 (OLR1) as a key regulator of autophagy and GATA4. A series of experiments manipulated OLR1 expression to investigate associated effects. Results demonstrated significantly increased senescent NP cells (NPCs) and compromised autophagy in IDD patients and animal models, with SASP closely linked to IDD progression. The aged disc milieu impeded autophagic GATA4 degradation, leading to elevated SASP expression in senescent NPCs. Restoring autophagy reversed senescence by degrading GATA4, hence disrupting the SASP cascade. Moreover, OLR1 was identified for its regulation of autophagy and GATA4 in senescent NPCs. Silencing OLR1 enhanced autophagic activity, suppressing GATA4-induced senescence and SASP expression in senescent NPCs. In conclusion, OLR1 was found to control autophagy-GATA4 and SASP, with targeted OLR1 inhibition holding promise in alleviating GATA4-induced senescence and SASP expression while delaying extracellular matrix degradation, offering a novel therapeutic approach for IDD management.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142038108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The effect of axenic dietary restriction on the age-related changes in C. elegans. 轴向饮食限制对 elegans 年龄相关变化的影响。
Ping Wu, Lieselot Vandemeulebroucke, Myriam Claeys, Wim Bert, Bart P Braeckman
{"title":"The effect of axenic dietary restriction on the age-related changes in C. elegans.","authors":"Ping Wu, Lieselot Vandemeulebroucke, Myriam Claeys, Wim Bert, Bart P Braeckman","doi":"10.1093/gerona/glae205","DOIUrl":"https://doi.org/10.1093/gerona/glae205","url":null,"abstract":"<p><p>Axenic dietary restriction (ADR) is highly effective in extending lifespan of C. elegans but its effects on healthspan improvement is less well characterized. Using transmission electron microscopy, morphometric analyses, and functional assays, we found ADR can preserve tissue ultrastructure, including the cuticle, epidermis, and intestinal lumen, and reduce age-associated pathologies like gonad degeneration, uterine tumor clusters, pharyngeal deterioration, and intestinal atrophy. However, there was no notable improvement in behavioral and functional metrics. Our results underscore that lifespan extension through ADR does not inherently translate to broad healthspan improvements.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Elevated C-Reactive Protein in Older Men with Chronic Pain: Association with Plasma Amyloid Levels and Hippocampal Volume. 患有慢性疼痛的老年男性体内 C 反应蛋白升高:与血浆淀粉样蛋白水平和海马体积的关系
Tyler R Bell, Carol E Franz, Kelsey R Thomas, Mc Kenna E Williams, Lisa T Eyler, Imanuel Lerman, Christine Fennema-Notestine, Olivia K Puckett, Stephen M Dorros, Matthew S Panizzon, Rahul C Pearce, Donald J Hagler, Michael J Lyons, Jeremy A Elman, William S Kremen
{"title":"Elevated C-Reactive Protein in Older Men with Chronic Pain: Association with Plasma Amyloid Levels and Hippocampal Volume.","authors":"Tyler R Bell, Carol E Franz, Kelsey R Thomas, Mc Kenna E Williams, Lisa T Eyler, Imanuel Lerman, Christine Fennema-Notestine, Olivia K Puckett, Stephen M Dorros, Matthew S Panizzon, Rahul C Pearce, Donald J Hagler, Michael J Lyons, Jeremy A Elman, William S Kremen","doi":"10.1093/gerona/glae206","DOIUrl":"https://doi.org/10.1093/gerona/glae206","url":null,"abstract":"<p><strong>Background: </strong>Chronic pain leads to tau accumulation and hippocampal atrophy, which may be moderated through inflammation. In older men, we examined associations of chronic pain with AD-related plasma biomarkers and hippocampal volume as moderated by systemic inflammation.</p><p><strong>Methods: </strong>Participants were men without dementia. Chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, we measured plasma amyloid-beta (Aβ42, n=871), Aβ40 (n=887), total tau (t-tau, n=841), and neurofilament light chain (NfL, n=915), and serum high-sensitivity C-reactive protein (hs-CRP, n=968), a marker of systemic inflammation. A subgroup underwent structural MRI to measure hippocampal volume (n=385). Analyses adjusted for medical morbidities, depressive symptoms, and opioid use.</p><p><strong>Results: </strong>Chronic pain related to higher Aβ40 (β=.25, p=.009), but hs-CRP was unrelated to AD-related biomarkers (ps>05). There was a significant interaction such that older men with both chronic pain and higher levels of hs-CRP had higher levels of Aβ42 (β=.36, p=.001) and Aβ40 (β=.29, p=.003). Chronic pain and hs-CRP did not interact to predict levels of Aβ42/Aβ40, t-tau, or NfL. Furthermore, there were significant interactions such that Aβ42 and Aβ40 were associated with lower hippocampal volume, particularly when levels of hs-CRP were elevated (hs-CRP*Aβ42: β=-.19, p=.002; hs-CRP*Aβ40: β=-.21, p=.001), regardless of chronic pain status.</p><p><strong>Conclusions: </strong>Chronic pain was associated with higher plasma Aβ, especially when hs-CRP was also elevated. Higher hs-CRP and Aβ levels were both related to smaller hippocampal volumes. Chronic pain, when accompanied by systemic inflammation, may elevate risk of neurodegeneration in AD-vulnerable regions.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142020051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Selection for late reproduction leads to loss of complex I mitochondrial capacity and associated increased longevity in seed beetles. 对晚期繁殖的选择导致甲壳虫线粒体复合体 I 能力的丧失以及相关寿命的延长。
Heather E Mast, Pierre U Blier, Mirko Ɖorđević, Uroš Savković, Claudia D Holody, Stephane L Bourque, Hélène Lemieux
{"title":"Selection for late reproduction leads to loss of complex I mitochondrial capacity and associated increased longevity in seed beetles.","authors":"Heather E Mast, Pierre U Blier, Mirko Ɖorđević, Uroš Savković, Claudia D Holody, Stephane L Bourque, Hélène Lemieux","doi":"10.1093/gerona/glae208","DOIUrl":"https://doi.org/10.1093/gerona/glae208","url":null,"abstract":"<p><p>Mitochondria play a key role in aging. Here, we measured integrated mitochondrial functions in experimentally evolved lines of the seed beetle Acanthoscelides obtectus that were selected for early (E) or late (L) reproduction for nearly four decades. The two lines have markedly different lifespans (8 days and 13 days in the E and L lines, respectively). The contribution of the NADH pathway to maximal flux was lower in the L compared to the E beetles at young stages, associated to increased control by complex I. In contrast, the contribution of the Succinate pathway was higher in the L than in the E line, while the Proline pathway showed no differences between the lines. Our data suggest that selection of age at reproduction leads to a modulation of complex I activity in mitochondria and that mitochondria are a functional link between evolutionary and mechanistic theories of aging.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Serum Transaminases And Older Adults: Distribution And Associations With All-Cause Mortality. 血清转氨酶与老年人:血清转氨酶与老年人:分布及其与全因死亡率的关系
Daniel Clayton-Chubb, Ammar Majeed, Stuart K Roberts, Hans G Schneider, Isabella Commins, Jessica Fitzpatrick, Robyn L Woods, Joanne Ryan, Sultana Monira Hussain, Natassia Tan, John S Lubel, Cammie Tran, Alexander D Hodge, John J McNeil, William W Kemp
{"title":"Serum Transaminases And Older Adults: Distribution And Associations With All-Cause Mortality.","authors":"Daniel Clayton-Chubb, Ammar Majeed, Stuart K Roberts, Hans G Schneider, Isabella Commins, Jessica Fitzpatrick, Robyn L Woods, Joanne Ryan, Sultana Monira Hussain, Natassia Tan, John S Lubel, Cammie Tran, Alexander D Hodge, John J McNeil, William W Kemp","doi":"10.1093/gerona/glae203","DOIUrl":"https://doi.org/10.1093/gerona/glae203","url":null,"abstract":"<p><strong>Background: </strong>Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are commonly ordered tests in general medical practice. However, their distribution and significance in older adults is understudied. As such, we aimed to evaluate sex-stratified distribution of both ALT and AST in older adults (≥ 70 years) and assess for associations with mortality.</p><p><strong>Methods: </strong>Post-hoc analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomised, placebo-controlled trial of daily low-dose aspirin for initially relatively healthy older persons. Univariate analysis and multiple logistic regression were used to explore baseline characteristics. Cox regression and restricted cubic splines were used to examine links between transaminase levels and mortality.</p><p><strong>Results: </strong>Of the 11853 participants with ALT and AST levels, 1054 (8.9%) deaths were recorded over median 6.4 (IQR 5.4-7.6) years. For ALT, the lowest quintiles for males and females were 6-15 U/L and 5-13 U/L respectively; for AST, the lowest quintiles were 8-18 U/L and 7-17 U/L. On both univariate and models adjusted for covariates including age, BMI, frailty, diabetes, and kidney disease, males and females in the lowest quintile of ALT had an increased hazard of mortality (aHR 1.51 [95% CI 1.14-1.99] and aHR 1.39 [95% CI 1.03-1.88] respectively). For the lowest quintile of AST, only males were at increased risk (aHR 1.33 [95% CI 1.04-1.70]). Associations remained significant when removing outliers.</p><p><strong>Conclusion: </strong>Low ALT levels independently confer an increased hazard of mortality for older males and females; low AST only impacted older male survival. Further evaluation of mechanisms would be worthwhile, and re-evaluating the lower limit of normal for ALT in older adults should be considered.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dietary Live Microbes Intake Associated with Biological Aging and Mortality. 膳食活微生物摄入量与生物衰老和死亡率的关系
Xu Zhu, Wenhang Chen, Jing Xue, Wenjie Dai, Rehanguli Maimaitituerxun, Yamin Liu, Hui Xu, Qiaoling Zhou, Quan Zhou, Chunyuan Chen, Zhenxing Wang, Hui Xie
{"title":"Dietary Live Microbes Intake Associated with Biological Aging and Mortality.","authors":"Xu Zhu, Wenhang Chen, Jing Xue, Wenjie Dai, Rehanguli Maimaitituerxun, Yamin Liu, Hui Xu, Qiaoling Zhou, Quan Zhou, Chunyuan Chen, Zhenxing Wang, Hui Xie","doi":"10.1093/gerona/glae202","DOIUrl":"https://doi.org/10.1093/gerona/glae202","url":null,"abstract":"<p><strong>Purpose: </strong>This observational study aimed to investigate associations between dietary live microbe intake and mortality, as well as biological aging.</p><p><strong>Methods: </strong>Adults from the 1999-2018 National Health and Nutrition Examination Survey were categorized into low, medium, and high dietary live microbe groups. Foods with medium and high live microbe content were aggregated into a medium-high consumption category. The outcomes included all-cause, cardiovascular, and cancer mortality, along with biological age (BA) acceleration assessed by the Klemera-Doubal method (KDM) and PhenoAge. Multiple regression analyses and mediation analyses were conducted to assess associations, adjusting for potential confounders.</p><p><strong>Results: </strong>A total of 34,133 adults were included in our analyses. Over an average follow-up period of 9.92 years, 5,462 deaths occurred. In multivariate adjusted models, every 100 grams of medium-high group foods consumed was associated with reduced all-cause mortality (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.91 to 0.97, P < 0.001) and cardiovascular mortality (HR 0.91, 95% CI 0.86 to 0.96, P < 0.001), but not with cancer mortality (HR 1.01, 95% CI 0.95 to 1.07, P = 0.768). Every 100 grams medium-high group foods consumption was associated with decreased KDM BA acceleration (fully adjusted regression coefficient -0.09, 95% CI -0.15 to -0.04, P = 0.001) and PhenoAge acceleration (fully adjusted regression coefficient -0.07, 95% CI -0.11 to -0.03, P < 0.001). Mediation analysis showed that BA acceleration partially mediated live microbes-mortality associations.</p><p><strong>Conclusion: </strong>Our results suggest that higher dietary live microbe intake is associated with lower mortality risk and slower biological aging. However, further research is needed to verify these findings.</p>","PeriodicalId":94243,"journal":{"name":"The journals of gerontology. Series A, Biological sciences and medical sciences","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142001666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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