Lifestyle mediates the role of nutrient-sensing pathways in cognitive aging: cellular and epidemiological evidence

• Published in: Communications biology 2020-04, Vol.3 (1), p.157, Article 157
• Main Authors: de Lucia, Chiara, Murphy, Tytus, Steves, Claire J., Dobson, Richard J. B., Proitsi, Petroula, Thuret, Sandrine
• Format: Article
• Language: English
• Subjects: 13; 13/100; 13/106; 14; 14/1; 38; 38/77; 631/378/2183/2182; 631/378/2612; Adult; Age Factors; Aged; Aged, 80 and over; Aging; Biology; Biomedical and Life Sciences; Cell Line; Cellular Senescence - genetics; Cognitive ability; Cognitive Aging; Diet Surveys; Diet, Healthy; Diet, Mediterranean; Energy Intake; Epidemiology; Exercise; Female; Gene expression; Gene Expression Regulation; Gene-Environment Interaction; Genetic Association Studies; Genetic diversity; GRB10 Adaptor Protein - genetics; GRB10 Adaptor Protein - metabolism; Healthy Aging - genetics; Healthy Aging - metabolism; Healthy Aging - pathology; Hippocampus - metabolism; Hippocampus - pathology; Humans; Life Sciences; Lifestyles; Male; Middle Aged; Molecular modelling; Neural stem cells; Neural Stem Cells - metabolism; Neural Stem Cells - pathology; Physical activity; Polymorphism, Single Nucleotide; Repressor Proteins - genetics; Repressor Proteins - metabolism; Risk Reduction Behavior; SIRT1 protein; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Stem cells; United Kingdom; Young Adult
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-0844-1

Aging induces cellular and molecular changes including modification of stem cell pools. In particular, alterations in aging neural stem cells (NSCs) are linked to age-related cognitive decline which can be modulated by lifestyle. Nutrient-sensing pathways provide a molecular basis for the link between lifestyle and cognitive decline. Adopting a back-translation strategy using stem cell biology to inform epidemiological analyses, here we show associations between cellular readouts of NSC maintenance and expression levels of nutrient-sensing genes following NSC exposure to aging human serum as well as morphological and gene expression alterations following repeated passaging. Epidemiological analyses on the identified genes showed associations between polymorphisms in SIRT1 and ABTB1 and cognitive performance as well as interactions between SIRT1 genotype and physical activity and between GRB10 genotype and adherence to a Mediterranean diet. Our study contributes to the understanding of neural stem cell molecular mechanisms underlying human cognitive aging and hints at lifestyle modifiable factors. Chiara de Lucia et al. investigate the relationships between genetic variants of nutrient-sensing gene candidates and their association with lifestyle factors and cognitive performance in a human cohort and the expression levels of those genes in in vitro model systems. They find that ABTB1 and GRB10 are key genes involved in aging, lifestyle, and cognitive performance.