Insulin Signaling and Dietary Restriction Differentially Influence the Decline of Learning and Memory with Age

Kauffman, Amanda; Ashraf, Jasmine; Corces, M. Ryan; Landis, Jessica; Murphy, Coleen T.

doi:10.1371/journal.pbio.1000372

Cited by 232 publications

(405 citation statements)

References 49 publications

Supporting

Mentioning

384

Contrasting

Unclassified

Order By: Relevance

“…DAF-16 also regulates multiple neuronal processes, including many different learning processes, sleep, morphology maintenance and axon regeneration (Kauffman et al, 2010;Tank et al, 2011;Toth et al, 2012;Murakami et al, 2005;Byrne et al, 2014;Nagy et al, 2014). A recent study delineated the neural targets of DAF-16 in C. elegans by comparing the transcriptomes of neurons that had been FACS sorted from wild type and insulin signaling-deficient (daf-16;daf-2) mutants (Kaletsky et al, 2016).…”

Section: Foxo In C Elegansmentioning

confidence: 99%

Fox transcription factors: from development to disease

2016

View full text Add to dashboard Cite

Forkhead box (Fox) transcription factors are evolutionarily conserved in organisms ranging from yeast to humans. They regulate diverse biological processes both during development and throughout adult life. Mutations in many Fox genes are associated with human disease and, as such, various animal models have been generated to study the function of these transcription factors in mechanistic detail. In many cases, the absence of even a single Fox transcription factor is lethal. In this Primer, we provide an overview of the Fox family, highlighting several key Fox transcription factor families that are important for mammalian development.

show abstract

Section: Foxo In C Elegansmentioning

confidence: 99%

Fox transcription factors: from development to disease

2016

View full text Add to dashboard Cite

show abstract

“…Worms with a loss of function mutation in the C. elegans homolog of CREB, crh-1, have smaller responses to tap than wild-type worms but show normal short-term habituation, but do not show long-term memory for tap habituation after spaced training at a 60-second ISI (Timbers & Rankin 2011) nor for a positive associative olfactory learning assay (Kauffman et al 2010).…”

Section: A Candidate Gene Approach To Dissociating Forms Of Learningmentioning

confidence: 99%

Genetic dissection of memory for associative and non‐associative learning in Caenorhabditis elegans

Lau

Timbers

Mahmoud³

et al. 2012

Genes Brain and Behavior

View full text Add to dashboard Cite

The distinction between non-associative and associative forms of learning has historically been based on the behavioral training paradigm. Through discovering the molecular mechanisms that mediate learning, we can develop a deeper understanding of the relationships between different forms of learning. Here, we genetically dissect short-and long-term memory for a non-associative form of learning, habituation and an associative form of learning, context conditioning for habituation, in the nematode Caenorhabditis elegans.

show abstract

“…DAF‐16 regulates learning and memory (Kauffman, Ashraf, Corces‐Zimmerman, Landis & Murphy, 2010; Murakami, Bessinger, Hellmann & Murakami, 2005), axonal degeneration and regeneration, and neurite outgrowth (Christensen, de la Torre‐Ubieta, Bonni & Colon‐Ramos, 2011). The hyperactivation of DAF‐16 in worm neurons is required for lifespan extension following loss of insulin‐like signaling (Wolkow, Kimura, Lee & Ruvkun, 2000).…”

Section: Introductionmentioning

confidence: 99%

FOXO protects against age‐progressive axonal degeneration

Hwang

Santo

et al. 2017

Aging Cell

View full text Add to dashboard Cite

SummaryNeurodegeneration resulting in cognitive and motor impairment is an inevitable consequence of aging. Little is known about the genetic regulation of this process despite its overriding importance in normal aging. Here, we identify the Forkhead Box O (FOXO) transcription factor 1, 3, and 4 isoforms as a guardian of neuronal integrity by inhibiting age‐progressive axonal degeneration in mammals. FOXO expression progressively increased in aging human and mouse brains. The nervous system‐specific deletion of Foxo transcription factors in mice accelerates aging‐related axonal tract degeneration, which is followed by motor dysfunction. This accelerated neurodegeneration is accompanied by levels of white matter astrogliosis and microgliosis in middle‐aged Foxo knockout mice that are typically only observed in very old wild‐type mice and other aged mammals, including humans. Mechanistically, axonal degeneration in nerve‐specific Foxo knockout mice is associated with elevated mTORC1 activity and accompanying proteotoxic stress due to decreased Sestrin3 expression. Inhibition of mTORC1 by rapamycin treatment mimics FOXO action and prevented axonal degeneration in Foxo knockout mice with accelerated nervous system aging. Defining this central role for FOXO in neuroprotection during mammalian aging offers an invaluable window into the aging process itself.

show abstract

Insulin Signaling and Dietary Restriction Differentially Influence the Decline of Learning and Memory with Age

Abstract: Novel C. elegans associative learning and memory assays reveal that insulin/IGF-1 signaling and dietary restriction pathways differentially maintain age-related memory decline by influencing expression levels of the transcription factor CREB.

Cited by 232 publications

References 49 publications

Fox transcription factors: from development to disease

Fox transcription factors: from development to disease

Genetic dissection of memory for associative and non‐associative learning in Caenorhabditis elegans

FOXO protects against age‐progressive axonal degeneration

Contact Info

Product

Resources

About