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 editors: Selenius, Jannica S.; Silveira, Patricia P.; Haapanen, Markus J.; von Bonsdorff, Mikaela; Lahti, Jari; Eriksson, Johan G.; Wasenius, Niko S.
Journal or series: Age and Ageing
ISSN: 0002-0729
eISSN: 1468-2834
Publication year: 2024
Publication date: 16/05/2024
Volume: 53
Issue number: 5
Article number: afae091
Publisher: Oxford University Press
Publication country: United Kingdom
Publication language: English
DOI: https://doi.org/10.1093/ageing/afae091
Publication open access: Openly available
Publication channel open access: Partially open access channel
Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/95327
Abstract
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.
Keywords: older people; ageing; insulin; receptors (biochemistry); genes; hippocampus; frailty syndrome; longitudinal research
Free keywords: insulin receptor (IR); frailty; hippocampal (hePRS); frailty index (FI); insulin receptor; older people
Contributing organizations
Ministry reporting: Yes
Reporting Year: 2024
Preliminary JUFO rating: 3
