title: Aging causes decreased resistance to multiple stresses and a failure to activate specific stress response pathways.
abstract: In this work, we examine the relationship between stress resistance and aging. We find that resistance to multiple types of stress peaks during early adulthood and then declines with age. To dissect the underlying mechanisms, we use C. elegans transcriptional reporter strains that measure the activation of different stress responses including: the heat shock response, mitochondrial unfolded protein response, endoplasmic reticulum unfolded protein response, hypoxia response, SKN-1-mediated oxidative stress response, and the DAF-16-mediated stress response. We find that the decline in stress resistance with age is at least partially due to a decreased ability to activate protective mechanisms in response to stress. In contrast, we find that any baseline increase in stress caused by the advancing age is too mild to detectably upregulate any of the stress response pathways. Further exploration of how worms respond to stress with increasing age revealed that the ability to mount a hormetic response to heat stress is also lost with increasing age. Overall, this work demonstrates that resistance to all types of stress declines with age. Based on our data, we speculate that the decrease in stress resistance with advancing age results from a genetically-programmed inactivation of stress response pathways, not accumulation of damage.
authors.affiliation: Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Dylan J
authors.initials: DJ
authors.lastname: Dues
authors.affiliation: Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Andrews
authors.affiliation: Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Claire E
authors.initials: CE
authors.lastname: Schaar
authors.affiliation: Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Alexis L
authors.initials: AL
authors.lastname: Bergsma
authors.affiliation: Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Senchuk
authors.affiliation: Laboratory of Aging and Neurodegenerative Disease, Center for Neurodegenerative Science, Van Andel Research Institute, Grand Rapids, MI 49503, USA.|Department of Translational Science and Molecular Medicine, Michigan State University, Grand Rapids, MI 49503, USA.|Department of Genetics, Michigan State University, East Lansing, MI 48824, USA.
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Van Raamsdonk
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D018869:Heat-Shock Response / Q000502:physiology*; D000860:Hypoxia / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological / Q000502:physiology*; D056811:Unfolded Protein Response / Q000502:physiology*
keywords: C. elegans; aging; heat shock response; hormesis; induced thermotolerance; stress resistance