Mitochondrial stress extends lifespan in C. elegans through neuronal hormesis.
Progressive neuronal deterioration accompanied by sensory functions decline is typically observed during aging. On the other hand, structural or functional alterations of specific sensory neurons extend lifespan in the nematode Caenorhabditis elegans. Hormesis is a phenomenon by which the body benefits from moderate stress of various kinds which at high doses are harmful. Several studies indicate that different stressors can hormetically extend lifespan in C. elegans and suggest that hormetic effects could be exploited as a strategy to slow down aging and the development of age-associated (neuronal) diseases in humans. Mitochondria play a central role in the aging process and hormetic-like bimodal dose-response effects on C. elegans lifespan have been observed following different levels of mitochondrial stress. Here we tested the hypothesis that mitochondrial stress may hormetically extend C. elegans lifespan through subtle neuronal alterations. In support of our hypothesis we find that life-lengthening dose of mitochondrial stress reduces the functionality of a subset of ciliated sensory neurons in young animals. Notably, the same pro-longevity mitochondrial treatments rescue the sensory deficits in old animals. We also show that mitochondrial stress extends C. elegans lifespan acting in part through genes required for the functionality of those neurons. To our knowledge this is the first study describing a direct causal connection between sensory neuron dysfunction and extended longevity following mitochondrial stress. Our work supports the potential anti-aging effect of neuronal hormesis and open interesting possibility for the development of therapeutic strategy for age-associated neurodegenerative disorders.
Institute for Clinical Chemistry and Laboratory Diagnostic, Medical Faculty of the Heinrich Heine University, Duesseldorf, Germany; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany; Department of Biomedicine and Prevention, Medical Faculty, University of Rome "Tor Vergata", Rome, Italy.
Silvia
S
Maglioni
IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany; Department of Biomedicine and Prevention, Medical Faculty, University of Rome "Tor Vergata", Rome, Italy.
Alfonso
A
Schiavi
Department of Biomedicine and Prevention, Medical Faculty, University of Rome "Tor Vergata", Rome, Italy.
Alessandra
A
Runci
Institute for Clinical Chemistry and Laboratory Diagnostic, Medical Faculty of the Heinrich Heine University, Duesseldorf, Germany; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany.
Anjumara
A
Shaik
Institute for Clinical Chemistry and Laboratory Diagnostic, Medical Faculty of the Heinrich Heine University, Duesseldorf, Germany; IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany; Department of Biomedicine and Prevention, Medical Faculty, University of Rome "Tor Vergata", Rome, Italy. Electronic address: natascia.ventura@uni-duesseldorf.de.
Natascia
N
Ventura
D000375:Aging / Q000378:metabolism*; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D016922:Cellular Senescence / Q000187:drug effects; D005838:Genotype; D059165:Hormesis; D008136:Longevity; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009043:Motor Activity; D009154:Mutation; D010641:Phenotype; D034622:RNA Interference; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D012903:Smell; D013312:Stress, Physiological; D013649:Taste
D029742:Caenorhabditis elegans Proteins
Aging; C. elegans; Chemotaxis; Ciliated sensory neurons; Hormesis; Mitochondria; Neurodegenerative disorders