RRC ID 59626
Author Xu A, Zhang Z, Ko SH, Fisher AL, Liu Z, Chen L.
Title Microtubule regulators act in the nervous system to modulate fat metabolism and longevity through DAF-16 in C. elegans.
Journal 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.
Volume 18(2)
Pages e12884
Published 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
Times Cited 3
C.elegans tm3124 tm5597