Pharmacology of Lifespan Extension

延长寿命的药理学

• 批准号: 9521330
• 负责人: Julie Kay Andersen
• 金额: $ 19.4万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-02-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9521330
• 关键词: Age of Onset; Aging; Animal Model; Biochemical; Caenorhabditis; Caenorhabditis elegans; Cell Line; Chemicals; Cholecalciferol; Chronic Disease; Clinical Research; Clinical Trials; Communities; Development; Disease; Dose; Drug Modelings; Elderly; Endoplasmic Reticulum; Exhibits; Functional disorder; Future; Genetic; Health; Homeostasis; Incidence; Intervention; Lead; Link; Longevity; Longevity Pathway; Mammalian Cell; Mammals; Modeling; Natural Products; Nematoda; Neurodegenerative Disorders; Pathology; Pathway interactions; Pharmaceutical Preparations; Pharmacology; Phenotype; Play; Population; Prevention; Preventive therapy; Proteins; Public Health; Research; Role; Secosteroids; Series; Structure; Technology; Testing; Vitamin D; Vitamin D Deficiency; Work; age related; amyloid formation; compound 30; drug discovery; high throughput screening; improved; novel; pre-clinical; pre-clinical research; prevent; protein structure; proteostasis; public health relevance; response; small molecule; small molecule libraries; successful intervention; therapy outcome; translational study

DESCRIPTION (provided by applicant): We have discovered a series of chemical compounds that delay the onset of age-related pathology and extend lifespan. These compounds were identified in focused chemical screens and high throughput screens of both synthetic compounds and natural products. Here we propose to identify the mechanism of lifespan extension with a focus on vitamin D which we have shown maintains protein homeostasis and extends lifespan in C. elegans. This will uncover novel mechanisms for interventions in aging and age-related disease.

描述（由申请人提供）：我们发现了一系列化合物，这些化合物延迟了与年龄相关的病理的发作并延长寿命。这些化合物在聚焦的化学筛选和合成化合物和天然产物的高吞吐量筛选中鉴定出来。在这里，我们建议确定寿命延伸的机理，重点是维生素D，我们显示的维生素D可以维持蛋白质稳态，并在秀丽隐杆线虫中延长了寿命。这将揭示有关衰老和与年龄相关疾病的干预措施的新型机制。

项目成果

Iron promotes protein insolubility and aging in C. elegans.

• DOI: 10.18632/aging.100689
• 发表时间: 2014-11
• 期刊: Aging
• 作者: Klang IM;Schilling B;Sorensen DJ;Sahu AK;Kapahi P;Andersen JK;Swoboda P;Killilea DW;Gibson BW;Lithgow GJ
• 通讯作者: Lithgow GJ

Kavain suppresses human Aβ-induced paralysis in C. elegans.

Kavain 抑制人 Aβ 诱导的线虫麻痹。

• DOI: 10.17912/micropub.biology.000254
• 发表时间: 2020
• 期刊: microPublication biology
• 作者: Chamoli,Manish;Chinta,ShankarJ;Andersen,JulieK;Lithgow,GordonJ
• 通讯作者: Lithgow,GordonJ

Drugs that target aging: how do we discover them?

抗衰老药物：我们如何发现它们？

• DOI: 10.1080/17460441.2019.1597049
• 发表时间: 2019
• 期刊: Expert opinion on drug discovery
• 影响因子: 6.3
• 作者: Myers,A;Lithgow,GJ
• 通讯作者: Lithgow,GJ

Vitamin D Promotes Protein Homeostasis and Longevity via the Stress Response Pathway Genes skn-1, ire-1, and xbp-1.

• DOI: 10.1016/j.celrep.2016.09.086
• 发表时间: 2016-10-25
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Mark KA;Dumas KJ;Bhaumik D;Schilling B;Davis S;Oron TR;Sorensen DJ;Lucanic M;Brem RB;Melov S;Ramanathan A;Gibson BW;Lithgow GJ
• 通讯作者: Lithgow GJ

Zinc Levels Modulate Lifespan through Multiple Longevity Pathways in Caenorhabditis elegans.

• DOI: 10.1371/journal.pone.0153513
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Kumar J;Barhydt T;Awasthi A;Lithgow GJ;Killilea DW;Kapahi P
• 通讯作者: Kapahi P