The Human Perception, Cognition, and Related Epigenetics

Special Article - Aging

Gerontol Geriatr Res. 2017; 3(1): 1030.

The Human Perception, Cognition, and Related Epigenetics

Bhadra U¹*, Das P² and Bhadra MP²

¹Centre for Cellular and Molecular Biology, Functional Genomics and Gene Silencing Group, Hyderabad, India

²Centre for Chemical Biology, Indian Institute of Chemical Technology, Hyderabad, India

*Corresponding author: Utpal Bhadra, Centre for Cellular and Molecular Biology, Functional Genomics and Gene Silencing Group, Uppal Road, Hyderabad-500 007, India

Received: May 29, 2017; Accepted: June 28, 2017; Published: July 05, 2017


The human brain represents a very complex network of synapses from about 85 billion neurons, which relay important functions of cognition besides other cellular and molecular processes by a multitude of genes and mechanisms. The epigenetic control occurring via changes in the modifications of the nucleosomal components, with no alteration in the DNA sequences is broadly covered, with respect to the alteration of cognitive traits. Normal aging processes occur with the alteration in the activity of the prefrontal cortex and hippocampus and with an increase in synaptic plasticity and neural circuitry. On the contrary, accumulation of various mutations of the DNA by the reactive oxygen species and other mitochondrial mutations accelerate the onset of brain aging with the simultaneous eruption of neurodegenerative diseases and dementia. This manuscript highlights modifications like DNA methylation, hydroxymethylation, histone methylation, acetylation, regulation by BDNF and non-coding RNAs, with details about the epigenetic changes contributing to neurodegeneration.

Keywords: Cognition; Aging; Epigenetic; Neurodegeneration; Non-coding RNAs


There are about 86 billion neurons in the human brain, which are from sets of large and small scale synaptic networks [1]. These networks form structures that function as networks for learning and cognition. There are a number of cellular and molecular mechanisms that act as key players in learning and memory. The de novo protein synthesis [2] is one such factor, which is under the control of the expression of a multitude of genes. These genes are in turn orchestrated by a wide array of mechanisms like the epigenetic ones [3] exhibited via modifications of Histone components, nucleosomal components, DNA and RNA molecules. Epigenetic processes are defined as biochemical processes that regulate gene expression without any alteration of the corresponding primary DNA sequence [4].

This review deals with the molecular mediators of epigenomic regulation, which mediate the phenotypic variability in complex behaviors like cognition to be precise. It represents numerous findings on the various histone modifiers particularly, DNA methylation and other epigenetic components. It provides an overview of the status of the field, with respect to both the practical and theory. Thus, it highlights the celebrated the role of epigenetic mechanisms in cognitive processes.

An overview of cognition

Cognition generally refers to the mental processes comprising the gain of knowledge and the ability to comprehend the same. It is a high-level function of the brain which encompasses the activities of thinking, remembering, knowing, judging and problem-solving using features like language, imagination, perception, and planning. According to Neisser (1967), cognition mainly involves:

a) Transforming sensory input

b) Reducing sensory information by means of selective remembrances,

c) Elaborating the information to make it understandable, and

d) storing and recovering information upon requirement,

e) using the information in our actions

Normal age-related memory loss

A normal aged individual show some symptoms of cognitive decline, which can be explained in two heads which are:

Altered activity of the prefrontal cortex and hippocampus: In the normal aging human population, there is a tendency of the reduction in the ability to recall verbal information [5]. Aging normally reduces the working memory, short-term recall, also the speed of information processing, as evident from a longitudinal study performed on subjects aged between 20 to 60 years [6,7]. The age-related memory loss across mammalian species also diminishes spatial memory, as evident in aged humans [8] monkeys, dogs [9], and mice [10]. However, normal aging does not affect the longterm memory of life history, implicit memory, the tendency to unconsciously respond to previously encountered information. Some processes of cognition, like the emotions, improve with aging and emotional stability is attained after the age of 60 due to changing the physiology of the medial prefrontal cortex [11]. Since the activation of the hippocampus is decreased in healthy aged adults, it diminishes the ability to perform tasks which involve recalling of memories or memorizing. Structurally, pathological memory loss is caused due to a loss in the volume of the medial temporal lobes, especially, the entorhinal cortex but in a normal age-related memory loss there is a loss of volume of the pre-frontal cortex [12].

Loss of neural circuits and synaptic plasticity: There is considerable loss of neurons of the neocortex and hippocampus due to aging [13]. An aging hippocampus shows a considerable loss of dendritic branching [14] in contrast to the dendritic branching being variable in the prefrontal cortex [13]. The density of the white matter of the prefrontal cortex and the anterior corpus callosum is also considerably reduced as measured by the diffusion tensor imaging [15]. It is supposed that with age, the frontal cortex create compromised the integrated circuits of the prefrontal cortex, hippocampus, and striatum [12]. Loss of the functional synapse can be responsible for the decline in cognition with age, and density of the synapse of the neurons of the frontal cortex show a significant decline, as evident in humans [16], rats [17] and monkeys [18]. The age-related synapse loss can be clearly seen in the dentate gyrus of the hippocampus, which leads to a loss in the spatial memory [19]. In the rat hippocampus, an impairment of LTP maintenance and induction show severe effects with them becoming susceptible to long-term depression [20]. Synaptic plasticity essential depends upon the regulation of neuronal calcium fluxes and calcium-mediated signaling pathways. Alteration of the calcium homeostasis in brain, therefore, might affect synaptic plasticity. The voltage-activated influx of calcium is increased in the CA1 neurons of the rat hippocampus due to an increase in the L-type calcium channel [21]. The intra neuronal calcium buffering capacity may get impaired due to an altered calcium channel which may increase the free calcium levels in the cytoplasm. The prefrontal cortex of the aging brain shows a reduction in the expression of the mRNA of calbindin1 and signaling proteins like calmodulin 1. These alterations in the expression of the gene thus affect the calcium homeostasis and affect the synaptic plasticity. Reduction in calbindin also makes the neurons more vulnerable to toxic effects such as excitotoxicity, that may lead to neurodegenerative disorders [22,23].

Accelerated Aging Syndromes

Accelerated aging due to faulty DNA repair

Normal age-related memory loss is differentiated from pathological memory loss by the degree of impairment as well as the rate of cognitive decline. Accelerated aging occurs with the inheritance of mutations in DNA repair genes, leading to symptoms called the segmental progeroid syndromes (Figure 1). They show an accelerated onset of a group of human aging phenotypes that include neurodegeneration [24].