Xiangru Xu PhD
Assistant Professor of Anesthesiology
Longevity genes; Epigenetics of brain aging and age-interventions
We are interested in the molecular mechanisms that underlie mammalian normal aging process. Currently, our research is focused on:
- Functional characterization of candidate longevity genes in worms;
- Understanding how epigenetic control mechanisms and epigenetic marks including DNA methylation and histone modifications underlie aging-related functional decline and the age-intervention strategies such as dietary restriction and rapamycin administration.
Our recent studies showed, for instance, that both the expression of DNA methyltransferases and the overall DNA methylation decline with brain aging, however, the age-associated loss of DNA methyltransferases and DNA methylation is preventable, at least partially, by dietary restriction and rapamycin. Regarding to histone modifications, we discovered a number of histone methylation/acetylation/phosphorylation changes with mouse brain aging. More interestingly, dietary restriction and rapamycin can rescue some of age-induced alterations of histone modifications. We have begun to investigate how epigenetic changes affect the cognitive functions, and to extend the epigenetic findings to the research of neurodegenerative disorders such as Alzheimer’s disease.
- Xu X. Single Cell Transcriptome Study in Brain Aging. J Single Cell Genomics Proteomics 2012, 1:2. doi: 10.4172
- Xu X, Mughal MR, Scott Hall F, Perona MT, Pistell PJ, Lathia JD, Chigurupati S, Becker KG, Ladenheim B, Niklason LE, Uhl GR, Cadet JL, Mattson MP. Dietary Restriction Mitigates Cocaine-Induced Alterations of Olfactory Bulb Cellular Plasticity and Gene Expression, and Behavior. J Neurochem. 2010 Jul; 114(1):323-34
- Guo Z, Jiang H, Xu X, Lyun T, Duan W, Mattson MP. Leptin-Mediated Cell Survival Signaling in Hippocampal Neurons Mediated by JAK /STAT3 and Mitochondrial Stabilization. Leptin-mediated cell survival signaling in hippocampal neurons mediated by Jak /Stat3 and mitochondrial stabilization. J Biol Chem. 2008 Jan 18;283(3):1754-63.
- Xu X, Zhan M, Duan W, Prabhu V, Brenneman R, Wood W, Firman J, Li H, Zhang P, Ibe C, Zonderman AB, Longo DL, Poosala S, Becker KG, Mattson MP. Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender. Genome Biol. 2007 Nov 7;8(11):R234
- Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, Lathia J, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP. Pivotal Role for Neuronal Toll-Like Receptors in Ischemic Brain Injury. Proc Natl Acad Sci U S A. 2007 Aug 21;104(34):13798-803.
- Zahn JM, Poosala S, Prabhu VV, Owen AB, Ingram DK, Lustig A, Weeraratna AT, Taub DD, Gorospe M, Mazan-Mamczarz K, Lakatta E, Boheler KR, Xu X, Mattson MP, Ko MS, Schlessinger D, Firman F, Wood WH, Longo DL, Kummerfeld SK, Zonderman AB, Kim SK, Becker KG. AGEMAP: a gene expression database for aging in mice. PLoS Genetics 2007 Nov;3(11):e201.