RT Journal Article
SR Electronic
T1 Life-long Dietary Restrictions have Negligible or Damaging Effects on Late-life Cognitive Performance: A Key Role for Genetics in Outcomes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.09.487742
DO 10.1101/2022.04.09.487742
A1 Andrew R. Ouellette
A1 Niran Hadad
A1 Andrew Deighan
A1 Laura Robinson
A1 Kristen O’Connell
A1 Adam Freund
A1 Gary A. Churchill
A1 Catherine C. Kaczorowski
YR 2022
UL http://biorxiv.org/content/early/2022/04/10/2022.04.09.487742.abstract
AB Several studies report that caloric restriction (CR) or intermittent fasting (IF) can improve cognition, while others report limited or no cognitive benefits. Here, we compare the effects of 20% CR, 40% CR, 1-day IF, and 2-day IF feeding paradigms to ad libitum controls (AL) on Y-maze working memory and contextual fear memory (CFM) in a large population of Diversity Outbred mice that model the genetic diversity of humans. While CR and IF interventions improve lifespan, we observed no enhancement of working memory or CFM in mice on these feeding paradigms, and report 40% CR to be damaging in the context of long-term memory. Using Quantitative Trait Loci mapping, we identified the gene Slc16a7 to be associated with late-life long-term memory outcomes in mice on lifespan promoting feeding paradigms. Limited utility of dieting and fasting on memory in mice that recapitulate genetic diversity in the human population highlights the need for anti-aging therapeutics that promote cognitive function, with a neuronal monocarboxylate transporter encoded by Slc16a7 highlighted as novel target.Competing Interest StatementAF is an employee of Calico Life Sciences, LLC, a for-profit biotechnology company focused on agingCRCaloric RestrictionIFIntermittent FastingDODiversity Outbred%SAPercent spontaneous AlternationsCFMContextual Fear MemoryCFAContextual Fear AcquisitionLODLog of OddsANOVAAnalysis of VarianceSEMStandard Error of Mean