This article is part of the Research Topic Neuronal Inputs and Outputs of Aging and Longevity


Front. Genet., 17 October 2012 | doi: 10.3389/fgene.2012.00212

The developing, aging neocortex: how genetics and epigenetics influence early developmental patterning and age-related change

  • Department of Psychology, University of California, Riverside, CA, USA

A hallmark of mammalian development is the generation of functional subdivisions within the nervous system. In humans, this regionalization creates a complex system that regulates behavior, cognition, memory, and emotion. During development, specification of neocortical tissue that leads to functional sensory and motor regions results from an interplay between cortically intrinsic, molecular processes, such as gene expression, and extrinsic processes regulated by sensory input. Cortical specification in mice occurs pre- and perinatally, when gene expression is robust and various anatomical distinctions are observed alongside an emergence of physiological function. After patterning, gene expression continues to shift and axonal connections mature into an adult form. The function of adult cortical gene expression may be to maintain neocortical subdivisions that were established during early patterning. As some changes in neocortical gene expression have been observed past early development into late adulthood, gene expression may also play a role in the altered neocortical function observed in age-related cognitive decline and brain dysfunction. This review provides a discussion of how neocortical gene expression and specific patterns of neocortical sensori-motor axonal connections develop and change throughout the lifespan of the animal. We posit that a role of neocortical gene expression in neocortex is to regulate plasticity mechanisms that impact critical periods for sensory and motor plasticity in aging. We describe results from several studies in aging brain that detail changes in gene expression that may relate to microstructural changes observed in brain anatomy. We discuss the role of altered glucocorticoid signaling in age-related cognitive and functional decline, as well as how aging in the brain may result from immune system activation. We describe how caloric restriction or reduction of oxidative stress may ameliorate effects of aging on the brain.

Keywords: cortical gene expression, intra-neocortical connections, brain anatomy, caloric restriction, aging

Citation: Huffman K (2012) The developing, aging neocortex: how genetics and epigenetics influence early developmental patterning and age-related change. Front. Gene. 3:212. doi: 10.3389/fgene.2012.00212

Received: 27 June 2012; Accepted: 26 September 2012;
Published online: 17 October 2012.

Edited by:

Elena G. Pasyukova, Institute of Molecular Genetics of Russian Academy of Sciences, Russia

Reviewed by:

Mahendra K. Thakur, Banaras Hindu University, India
Yousin Suh, Albert Einstein College of Medicine, USA
Shin Murakami, Touro University-California, USA
Gennady Ermak, The University of Southern California, USA

Copyright: © 2012 Huffman. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.

*Correspondence: Kelly Huffman, Department of Psychology, University of California, Riverside, 900 University Avenue, Riverside, CA 92521, USA. e-mail:

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