Mechanisms of stem cell preservation and lifespan extension in Drosophila

果蝇干细胞保存和寿命延长的机制

• 批准号: 10625313
• 负责人: Denise J. Montell
• 金额: $ 31.88万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625313
• 关键词: Adult; Affect; Aging; Animals; Behavioral; Binding; Biological Assay; Caenorhabditis elegans; Candidate Disease Gene; Classification; Cues; Data; Development; Developmental Gene; Diapause; Drosophila genus; Feeding behaviors; Female; Fertility; Genes; Genetic; Genetic study; Goals; Growth; Human; Individual; Insulin; Insulin Receptor; Longevity; Maintenance; Metabolism; Methods; Molecular; Mus; Oogenesis; Organism; Pathway interactions; Persons; Process; Proxy; Public Health; Recovery; Regulation; Rejuvenation; Reproduction; Resistance; Stress; System; Temperature; Testing; Tissues; Work; axonal pathfinding; candidate identification; circadian; cold temperature; day length; experience; feeding; female fertility; fertility preservation; fly; follow-up; gene network; genetic approach; genome wide association study; germline stem cells; healthspan; insight; knock-down; model organism; mutant; neurodevelopment; neuron development; novel; nutrient deprivation; preservation; programs; reproductive; response; stem cells; timeline; tool

Across many species, including humans, one of the many consequences of aging is a reduction in fertility, particularly female fertility. Intriguingly some species can preserve fertility for longer than they otherwise would, under specific environmental conditions. For example, various species of Drosophila enter a state called adult reproductive diapause when they experience low temperatures and short day length. Under these conditions they can double their lifespan while maintaining fertility. Previous work has implicated a few genes in positive or negative regulation of adult reproductive diapause in Drosophila. For example, the insulin pathway negatively regulates diapause, suggesting mechanisms that are conserved with the regulation of metabolism, fertility, and lifespan in other species including C. elegans, mice, and humans. However, our mechanistic understanding of diapause is extremely limited, and how fertility is preserved is unknown. We have taken advantage of powerful genetic tools in Drosophila to carry out a genome-wide association study of diapause. This approach appears to be highly successful, as the few known genes emerged from the analysis, such as the insulin receptor. In addition, this screen revealed that the most highly enriched networks of genes associated with diapause include those involved in neuronal development and female reproduction. The neuronal development genes are striking, as they have not previously been associated with diapause and thus offer to provide new molecular and cellular insights. Here we propose to: 1) identify the genes controlling specific steps in the diapause program such as entry, maintenance, exit, preservation of fecundity, and lifespan; 2) test whether diapause genes are required during development to prepare the animals for diapause, or function specifically in adulthood; and 3) investigate the molecular mechanisms of germline stem cell preservation during diapause. We anticipate that just as studies of C. elegans dauer formation illuminated general pathways regulating metabolism, growth, reproduction and aging in animals ranging from worms to humans, studies of Drosophila diapause offer the exciting potential to uncover novel and general mechanisms of stem cell preservation, fertility maintenance, and lifespan extension.

在包括人类在内的许多物种中，衰老的许多后果之一是

项目成果

A kinase gets caspases into shape.

激酶使半胱天冬酶成形。

• DOI: 10.1016/j.cell.2006.07.017
• 发表时间: 2006
• 期刊: Cell
• 影响因子: 64.5
• 作者: Montell,DeniseJ

Genes that drive invasion and migration in Drosophila.

驱动果蝇入侵和迁移的基因。

• DOI: 10.1016/j.gde.2003.12.001
• 发表时间: 2004
• 期刊: Current opinion in genetics & development
• 影响因子: 4
• 作者: Starz-Gaiano,Michelle;Montell,DeniseJ
• 通讯作者: Montell,DeniseJ

Cell survival following direct executioner-caspase activation.

直接刽子手半胱天冬酶激活后的细胞存活。

• DOI: 10.1073/pnas.2216531120
• 发表时间: 2023-01-24
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Nano, Maddalena;Mondo, James A.;Harwood, Jacob;Balasanyan, Varuzhan;Montell, Denise J.
• 通讯作者: Montell, Denise J.

Laser ablation studies of the role of the Drosophila oocyte nucleus in pattern formation.

激光消融研究果蝇卵母细胞核在模式形成中的作用。

• DOI: 10.1126/science.254.5029.290
• 发表时间: 1991
• 期刊: Science (New York, N.Y.)
• 作者: Montell,DJ;Keshishian,H;Spradling,AC
• 通讯作者: Spradling,AC

Analysis of cell migration using Drosophila as a model system.

• DOI: 10.1385/1-59259-860-9:175
• 发表时间: 2005
• 期刊: Methods in molecular biology
• 作者: J. McDonald;D. Montell