RT Journal Article
T1 PAS kinase deficiency reduces aging effects in mice
A1 Dongil, Pilar
A1 Pérez García, Ana
A1 Hurtado Carneiro, Verónica
A1 Herrero de Dios, Carmen
A1 Álvarez García, Elvira
A1 Sanz Miguel, María Del Carmen
AB Several signaling pathways may be affected during aging. All are regulated by nutrient levels leading to a decline in mitochondrial function and autophagy and to an increase in oxidative stress. PAS Domain Kinase (PASK) is a nutrient and bioenergetic sensor. We have previously found that PASK plays a role in the control of hepatic metabolic balance and mitochondrial homeostasis. To investigate PASK’s role in hepatic oxidative stress during aging, we analyzed the mitochondrial function, glucose tolerance, insulin resistance, and lipid-related parameters in aged PASK-deficient mice. Hepatic Pask mRNA decreased in step with aging, being undetectable in aged wild-type (WT) mice. Aged PASK-deficient mice recorded lower levels of ROS/RNS compared to aged WT. The regulators of mitochondrial biogenesis, PGC1a, SIRT1 and NRF2, decreased in aged WT, while aged PASK-deficient mice recorded a higher expression of NRF2, GCLm and HO1 proteins and CS activity under fasted conditions. Additionally, aged PASK-deficient mice recorded an overexpression of the longevity gene FoxO3a, and maintained elevated PCNA protein, suggesting that hepatic cell repair mechanisms might be functional. PASK-deficient mice have better insulin sensitivity and no glucose intolerance, as confirmed by a normal HOMA-IR index. PASK may be a good target for reducing damage during aging.
PB Impact Journals, LLC.
SN 1945-4589
YR 2020
FD 2020-01-23
LK https://hdl.handle.net/20.500.14352/107774
UL https://hdl.handle.net/20.500.14352/107774
LA eng
NO Dongil P, Pérez-García A, Hurtado-Carneiro V, Herrero-de-Dios C, Álvarez E, Sanz C. PAS kinase deficiency reduces aging effects in mice. Aging (Albany NY). 2020 Jan 23; 12:2275-2301 . https://doi.org/10.18632/aging.102745
NO Universidad Complutense-Programa de Financiación Banco Santander para la Creación y Consolidación de Equipos de Investigación [GR3/14]Fondos FEDER
NO Universidad Complutense de Madrid
NO Ministerio de Economía, Comercio y Empresa (España)
NO European Commission
NO Banco Santander
NO Fundación Mutua Madrileña de Investigación Médica
NO Instituto de Salud Carlos III (España)
DS Docta Complutense
RD 28 sept 2024