Journal Article

The decrease of intraflagellar transport impairs sensory perception and metabolism in ageing

Zhang, Yincong, Dai, Yumin, Zhou, Jun, Zhou, Yifei, Shen, Yidong, Zhang, Xiaona, Song, Mengjiao, Yan, Xiumin

2021

Overview

Sensory perception and metabolic homeostasis are known to deteriorate with ageing, impairing the health of aged animals, while mechanisms underlying their deterioration remain poorly understood. The potential interplay between the declining sensory perception and the impaired metabolism during ageing is also barely explored. Here, we report that the intraflagellar transport (IFT) in the cilia of sensory neurons is impaired in the aged nematode Caenorhabditis elegans due to a daf-19 /RFX-modulated decrease of IFT components. We find that the reduced IFT in sensory cilia thus impairs sensory perception with ageing. Moreover, we demonstrate that whereas the IFT-dependent decrease of sensory perception in aged worms has a mild impact on the insulin/IGF-1 signalling, it remarkably suppresses AMP-activated protein kinase (AMPK) signalling across tissues. We show that upregulating daf-19 /RFX effectively enhances IFT, sensory perception, AMPK activity and autophagy, promoting metabolic homeostasis and longevity. Our study determines an ageing pathway causing IFT decay and sensory perception deterioration, which in turn disrupts metabolism and healthy ageing. Sensory perception and metabolic homeostasis are known to deteriorate with ageing, while mechanisms underlying their deterioration remain poorly understood. Here, the authors demonstrate that decrease of intraflagellar transport in the cilia of sensory neurons impairs sensory perception and metabolism in ageing C. elegans .

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 14 / 38 / 42 / 631/136/7 / 631/1647/334/1582/712 / 631/57/343/1361 / 631/80/128/1383 / 631/80/39 / 64/11 / 96 / Aging / AMP / AMP-activated protein kinase / AMP-Activated Protein Kinases - genetics / AMP-Activated Protein Kinases - metabolism / Animals / Animals, Genetically Modified / Autophagy / Biological Transport / Caenorhabditis elegans - genetics / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Cilia / Cilia - metabolism / Flagella - metabolism / Homeostasis / Humanities and Social Sciences / Insulin / Insulin-like growth factor I / Insulin-Like Growth Factor I - genetics / Insulin-Like Growth Factor I - metabolism / Kinases / Longevity - genetics / Metabolism / multidisciplinary / Nematodes / Neurons / Perception / Perception - physiology / Phagocytosis / Regulatory Factor X1 - genetics / Regulatory Factor X1 - metabolism / RNA Interference / Science / Science (multidisciplinary) / Sensory neurons / Sensory perception / Sensory Receptor Cells - metabolism / Sensory Receptor Cells - physiology / Signal transduction / Signal Transduction - genetics / Signal Transduction - physiology / Signaling / Transcription Factors - genetics / Transcription Factors - metabolism / Worms