論文 - 詳細
| RRC ID | 59626 |
|---|---|
| 著者 | Xu A, Zhang Z, Ko SH, Fisher AL, Liu Z, Chen L. |
| タイトル | Microtubule regulators act in the nervous system to modulate fat metabolism and longevity through DAF-16 in C. elegans. |
| ジャーナル | Aging Cell |
| Abstract |
Microtubule (MT) regulation is involved in both neuronal function and the maintenance of neuronal structure, and MT dysregulation appears to be a general downstream indicator and effector of age-related neurodegeneration. But the role of MTs in natural aging is largely unknown. Here, we demonstrate a role of MT regulators in regulating longevity. We find that loss of EFA-6, a modulator of MT dynamics, can delay both neuronal aging and extend the lifespan of C. elegans. Through the use of genetic mutants affecting other MT-regulating genes in C. elegans, we find that loss of MT stabilizing genes (including ptrn-1 and ptl-1) shortens lifespan, while loss of MT destabilizing gene hdac-6 extends lifespan. Via the use of tissue-specific transgenes, we further show that these MT regulators can act in the nervous system to modulate lifespan. Through RNA-seq analyses, we found that genes involved in lipid metabolism were differentially expressed in MT regulator mutants, and via the use of Nile Red and Oil Red O staining, we show that the MT regulator mutants have altered fat storage. We further find that the increased fat storage and extended lifespan of the long-lived MT regulator mutants are dependent on the DAF-16/FOXO transcription factor. Our results suggest that neuronal MT status might affect organismal aging through DAF-16-regulated changes in fat metabolism, and therefore, MT-based therapies might represent a novel intervention to promote healthy aging. |
| 巻・号 | 18(2) |
| ページ | e12884 |
| 公開日 | 2019-4-1 |
| DOI | 10.1111/acel.12884 |
| PMID | 30638295 |
| PMC | PMC6413656 |
| MeSH | Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Forkhead Transcription Factors / metabolism* Healthy Aging Longevity* Nervous System / metabolism* |
| IF | 7.346 |
| 引用数 | 3 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 6 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm3124 tm5597 |