Impact of abnormal steroid metabolome on cellular senescence, frailty and cognition

类固醇代谢异常对细胞衰老、虚弱和认知的影响

• 批准号: 10586100
• 负责人: Irina Bancos
• 金额: $ 11.93万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10586100
• 关键词: Acceleration; Adrenal Gland Adenoma; Adrenal Gland Diseases; Adrenal Gland Hyperfunction; Adrenal Glands; Adult; Affect; Age; Aging; Award; Biological Markers; CDKN2A gene; Cardiovascular system; Cell Aging; Chronology; Clinic; Cognition; Cognitive; Data; Dementia; Dexamethasone; Diagnosis; Elderly; Enrollment; Foundations; Fracture; Hydrocortisone; Impaired cognition; Incidence; Individual; Institution; Interleukin-6; Intervention Studies; Link; Measurement; Measures; Mentored Patient-Oriented Research Career Development Award; Mentorship; Morbidity - disease rate; Muscle Weakness; National Institute of Diabetes and Digestive and Kidney Diseases; Patients; Pilot Projects; Population; Prognostic Marker; Prospective Studies; Reporting; Research; Resources; Risk; Short-Term Memory; Steroids; Structure; Symptoms; United States National Institutes of Health; Urine; Work; age difference; cognitive function; diagnostic biomarker; executive function; experience; falls; frailty; functional decline; glycation; metabolome; mortality; multidisciplinary; novel; potential biomarker; prevent; processing speed; senescence; sex; steroid metabolism; therapy design; therapy development

PROJECT SUMMARY/ABSTRACT Mild autonomous cortisol secretion (MACS) is diagnosed in up to 50% of patients with adrenal adenomas1, affecting 1-2% of adult population. MACS is diagnosed based on abnormal cortisol following dexamethasone suppression; however, 24h urine cortisol concentrations are usually normal. As we recently showed in the work sponsored by the current NIDDK K23 award, patients with MACS demonstrate higher incidence of fractures and report more falls and symptoms of muscle weakness. In our preliminary data we show that when assessed by a comprehensive multi-steroid panel, patients with MACS demonstrate a unique steroid signature that is similar to aging adults without adrenal adenomas. We further found that patients with MACS demonstrate lower cognition and increased frailty and increased senescence biomarkers. Our overall objective of this project is to understand the link between the abnormal steroid signature and cognitive function, overall frailty, and biomarkers of cellular senescence. In Aim 1, the domains and the extent of cognitive impairment will be characterized in patients with MACS, and the association of cognitive function to accelerated adrenal aging, as measured by the steroid metabolome will be determined. In Aim 2, the association of cognitive impairment with frailty, advanced glycation products, and biomarkers of senescence will be determined. The proposed research will take advantage of the current structure and detailed characterization of subjects enrolled as part of the K23 NIDDK award as well as another ongoing prospective study of patients with overt hypercortisolism. The exceptional resources and institutional support at Mayo Clinic, outstanding multi- disciplinary mentorship and collaborative team, will allow advancement in understanding the steroid signature associated with cognitive decline that may serve as a diagnostic and prognostic biomarker of cognitive impairment and frailty.

项目总结/摘要 高达50%的肾上腺腺瘤患者被诊断为轻度自主性皮质醇分泌（MACS）1， 影响1-2%的成年人。MACS的诊断是基于地塞米松后皮质醇异常 抑制;然而，24小时尿皮质醇浓度通常正常。正如我们最近在工作中所展示的那样， 由目前的NIDDK K23奖赞助，MACS患者的骨折发生率较高 并报告更多的福尔斯和肌肉无力症状。我们的初步数据显示， 通过全面的多类固醇小组，MACS患者表现出独特的类固醇特征，即 类似于没有肾上腺腺瘤的老年人。我们进一步发现，MACS患者表现出 认知能力降低，虚弱程度增加，衰老生物标志物增加。 我们这个项目的总体目标是了解异常类固醇信号与 认知功能、整体虚弱和细胞衰老的生物标志物。在目标1中， 认知功能障碍的特征将在MACS患者中表现出来，认知功能与 将确定加速的肾上腺老化，如通过类固醇代谢组测量的。在目标2中， 认知障碍与虚弱、晚期糖基化产物和衰老生物标志物的关系 将被确定。 拟议的研究将利用目前的结构和详细的特点的主题 作为K23 NIDDK奖的一部分，以及另一项正在进行的对显性遗传患者的前瞻性研究 皮质醇过多症马约诊所的特殊资源和机构支持，出色的多功能， 学科指导和协作团队，将允许在理解类固醇签名的进步 与认知能力下降相关，可作为认知能力下降的诊断和预后生物标志物。 损伤和脆弱。

项目成果

Glucocorticoid withdrawal syndrome following surgical remission of endogenous hypercortisolism: a longitudinal observational study.

内源性皮质醇增多症手术缓解后糖皮质激素戒断综合征：一项纵向观察研究。

• DOI: 10.1093/ejendo/lvad073
• 发表时间: 2023
• 期刊: European journal of endocrinology
• 影响因子: 5.8
• 作者: Zhang,CatherineD;Li,Dingfeng;Singh,Sumitabh;Suresh,Malavika;Thangamuthu,Karthik;Nathani,Rohit;Achenbach,SaraJ;Atkinson,ElizabethJ;VanGompel,JamieJ;Young,WilliamF;Bancos,Irina
• 通讯作者: Bancos,Irina

Determinants of muscle function and health-related quality of life in patients with endogenous hypercortisolism: a cross-sectional study.

内源性皮质醇增多症患者肌肉功能和健康相关生活质量的决定因素：一项横断面研究。

• DOI: 10.1093/ejendo/lvad069
• 发表时间: 2023
• 期刊: European journal of endocrinology
• 影响因子: 5.8
• 作者: Li,Dingfeng;Zhang,CatherineD;Saini,Jasmine;Singh,Sumitabh;Nathani,Rohit;Thangamuthu,Karthik;Suresh,Malavika;Atkinson,ElizabethJ;Achenbach,SaraJ;VanGompel,Jamie;Young,WilliamF;Bancos,Irina
• 通讯作者: Bancos,Irina

In Situ Metabolomics of Cortisol-Producing Adenomas.

• DOI: 10.1093/clinchem/hvac191
• 发表时间: 2023-02-01
• 期刊: Clinical chemistry
• 影响因子: 9.3

Risk of dementia and psychiatric or sleep disorders after diagnosis of adrenal adenomas: a population-based cohort study.

肾上腺腺瘤诊断后痴呆和精神或睡眠障碍的风险：一项基于人群的队列研究。

• DOI: 10.1093/ejendo/lvad135
• 发表时间: 2023
• 期刊: European journal of endocrinology
• 影响因子: 5.8
• 作者: Li,Dingfeng;Singh,Sumitabh;Zhang,CatherineD;Kaur,RavinderJeet;Ebbehoj,Andreas;Atkinson,ElizabethJ;Achenbach,SaraJ;Stricker,NikkiH;Mielke,MichelleM;Rocca,Walter;Bancos,Irina
• 通讯作者: Bancos,Irina