A1 Journal article (refereed)
The brain insulin receptor gene network and associations with frailty index (2024)

Selenius, J. S., Silveira, P. P., Haapanen, M. J., von Bonsdorff, M., Lahti, J., Eriksson, J. G., & Wasenius, N. S. (2024). The brain insulin receptor gene network and associations with frailty index. Age and Ageing, 53(5), Article afae091. https://doi.org/10.1093/ageing/afae091

JYU authors or editors

Publication details

All authors or editorsSelenius, Jannica S.; Silveira, Patricia P.; Haapanen, Markus J.; von Bonsdorff, Mikaela; Lahti, Jari; Eriksson, Johan G.; Wasenius, Niko S.

Journal or seriesAge and Ageing



Publication year2024

Publication date16/05/2024


Issue number5

Article numberafae091

PublisherOxford University Press

Publication countryUnited Kingdom

Publication languageEnglish


Publication open accessOpenly available

Publication channel open accessPartially open access channel

Publication is parallel published (JYX)https://jyx.jyu.fi/handle/123456789/95327


Objective: To investigate longitudinal associations between variations in the co-expression-based brain insulin receptor polygenic risk score and frailty, as well as change in frailty across follow-up.

Methods: This longitudinal study included 1605 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network, which measure genetic variation in the function of the insulin receptor, were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Frailty was assessed in at baseline in 2001–2004, 2011–2013 and 2017–2018 by applying a deficit accumulation-based frailty index. Analyses were carried out by applying linear mixed models and logistical regression models adjusted for adult socioeconomic status, birthweight, smoking and their interactions with age.

Results: The FI levels of women were 1.19%-points (95% CI 0.12–2.26, P = 0.029) higher than in men. Both categorical and continuous hePRS-IR in women were associated with higher FI levels than in men at baseline (P < 0.05). In women with high hePRS-IR, the rate of change was steeper with increasing age compared to those with low or moderate hePRS-IR (P < 0.05). No associations were detected between mePRS-IR and frailty at baseline, nor between mePRS-IR and the increasein mean FI levels per year in either sex (P > 0.43).

Conclusions: Higher variation in the function of the insulin receptor gene network in the hippocampus is associated with increasing frailty in women. This could potentially offer novel targets for future drug development aimed at frailty and ageing.

Keywordsolder peopleageinginsulinreceptors (biochemistry)geneshippocampusfrailty syndromelongitudinal research

Free keywordsinsulin receptor (IR); frailty; hippocampal (hePRS); frailty index (FI); insulin receptor; older people

Contributing organizations

Ministry reportingYes

Reporting Year2024

Preliminary JUFO rating3

Last updated on 2024-02-07 at 23:25