Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans.
Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(-) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence.
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA; Calico Life Sciences, 1170 Veterans Boulevard, South San Francisco, CA 94080, USA.
Antoine E
AE
Roux
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
Kelley
K
Langhans
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
Walter
W
Huynh
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA; Calico Life Sciences, 1170 Veterans Boulevard, South San Francisco, CA 94080, USA. Electronic address: cynthia@calicolabs.com.
Cynthia
C
Kenyon
D000375:Aging / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005247:Feeding Behavior; D007814:Larva / Q000502:physiology; D010641:Phenotype; D066329:Protein Aggregates; D013312:Stress, Physiological; D056811:Unfolded Protein Response / Q000235:genetics
D029742:Caenorhabditis elegans Proteins; D066329:Protein Aggregates