Delaying aging in Caenorhabditis elegans with protein aggregation inhibitors.
Recent evidence suggests that during aging there is widespread accumulation of aggregated insoluble proteins, even in the absence of pathological conditions. Pharmacological manipulation of protein aggregation might be helpful to unveil the involvement of protein aggregates during aging, as well as to develop novel strategies to delay aging. Here we investigated the effect of known protein aggregation inhibitors on the lifespan and health-span of Caenorhabditis elegans. For this purpose, we selected various structurally diverse anti-aggregation compounds and screened them in liquid and solid medium for their ability to alter the rate of aging in vivo. Our results show that treatment of C. elegans with diverse aggregation inhibitors significantly increases the animal lifespan and health-span. These findings indicate that protein misfolding and aggregation may play an important role in cellular dysfunction during aging, opening a novel approach to increase longevity and enhance the quality of life during aging.
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA; Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Pue, Mexico.
Karina
K
Cuanalo-Contreras
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA.
Kyung-Won
KW
Park
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA.
Abhisek
A
Mukherjee
Laboratorio de Bioquímica y Biología Molecular, Centro de Química, Instituto de Ciencias, Benemérita Universidad Autónoma de Puebla, Puebla, Pue, Mexico.
Lourdes
L
Millán-Pérez Peña
Mitchell Center for Alzheimer's Disease and Related Brain Disorders, Department of Neurology, University of Texas Houston Medical School, 6431 Fannin St, Houston, TX 77030, USA. Electronic address: Claudio.Soto@uth.tmc.edu.
Claudio
C
Soto
D000375:Aging / Q000187:drug effects* / Q000502:physiology*; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008136:Longevity; D066329:Protein Aggregates / Q000187:drug effects* / Q000502:physiology*
D066329:Protein Aggregates
Aggregation inhibitors; Aging; C. elegans; Lifespan; Protein misfolding