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Dichotomous Responses to Chronic Fetal Hypoxia Lead to a Predetermined Aging Phenotype
- Source :
- Molecular & Cellular Proteomics, Rudloff, Stefan; Bileck, Andrea; Janker, Lukas; Wanner, Nicola; Liaukouskaya, Nastassia; Lundby, Carsten; Huber, Tobias B.; Gerner, Christopher; Huynh-Do, Uyen (2022). Dichotomous Responses to Chronic Fetal Hypoxia Lead to a Predetermined Aging Phenotype. Molecular & cellular proteomics, 21(2), p. 100190. American Society for Biochemistry and Molecular Biology 10.1016/j.mcpro.2021.100190
- Publication Year :
- 2022
- Publisher :
- Elsevier BV, 2022.
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Abstract
- Hypoxia-induced intrauterine growth restriction increases the risk for cardiovascular, renal, and other chronic diseases in adults, representing thus a major public health problem. Still, not much is known about the fetal mechanisms that predispose these individuals to disease. Using a previously validated mouse model of fetal hypoxia and bottom-up proteomics, we characterize the response of the fetal kidney to chronic hypoxic stress. Fetal kidneys exhibit a dichotomous response to chronic hypoxia, comprising on the one hand cellular adaptations that promote survival (glycolysis, autophagy, and reduced DNA and protein synthesis), but on the other processes that induce a senescence-like phenotype (infiltration of inflammatory cells, DNA damage, and reduced proliferation). Importantly, chronic hypoxia also reduces the expression of the antiaging proteins klotho and Sirt6, a mechanism that is evolutionary conserved between mice and humans. Taken together, we uncover that predetermined aging during fetal development is a key event in chronic hypoxia, establishing a solid foundation for Barker's hypothesis of fetal programming of adult diseases. This phenotype is associated with a characteristic biomarker profile in tissue and serum samples, exploitable for detecting and targeting accelerated aging in chronic hypoxic human diseases.
Details
- ISSN :
- 15359476
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Molecular & Cellular Proteomics
- Accession number :
- edsair.doi.dedup.....02543fe00d74ef4a9b1a8dcc5e4c6437