to cause the disorder. The human brain shows a decline in function and a change in gene expression. This modulation in gene expression may be due to oxidative DNA damage at promoter regions in the genome. Genes that are down-regulated over the age of 40 include: GluR1 AMPA receptor subunit NMDA R2A receptor subunit (involved in learning) Subunits of the GABA-A receptor Genes involved in long-term potentiation e.g. calmodulin 1 and CAM kinase II alpha. Calcium signaling genes Synaptic plasticity genes Synaptic vesicle release and recycling genes Genes that are upregulated include: Genes associated with stress response and DNA repair Antioxidant defence Epigenetic age analysis of brain regions The cerebellum is the youngest brain region (and probably body part) in centenarians according to an epigenetic biomarker of tissue age known as epigenetic clock: it is about 15 years younger than expected in a centenarian. By contrast, all brain regions and brain cells appear to have roughly the same epigenetic age in subjects who are younger than 80. These findings suggest that the cerebellum is protected from aging effects, which in turn could explain why the cerebellum exhibits fewer neuropathological hallmarks of age related dementias compared to other brain regions. Delaying the effects of aging The process of aging may be inevitable; however, one may potentially delay the effects and severity of this progression. While there is no consensus of efficacy, the following are reported as delaying cognitive decline: High level of education Physical exercise Staying intellectually engaged, i.e. reading and mental activities (such as crossword puzzles) Maintaining social and friendship networks Maintaining a healthy diet, including omega-3 fatty acids, protective antioxidants and e.g. flavonols-containing foods as well as potentially anthocyanins- and flavanones-containing ones as in, more generally, Mediterranean diet patterns "Super Agers" Longitudinal research studies have recently conducted genetic analyses of centenarians and their offspring to identify biomarkers as protective factors against the negative effects of aging. In particular, the cholesteryl ester transfer protein (CETP) gene is linked to prevention of cognitive decline and Alzheimer's disease. Specifically, valine CETP homozygotes but not heterozygotes experienced a relative 51% less decline in memory compared to a reference group after adjusting for demographic factors and APOE status. Cognitive reserve The ability of an individual to demonstrate no cognitive signs of aging despite an aging brain is called cognitive reserve. This hypothesis suggests that two patients might have the same brain pathology, with one