Journal of Medicine and Medical Science Vol. 2(3) pp. 696-713, March 2011 Available online @http://www.interesjournals.org/JMMS Copyright © 2011 International Research Journals Review Epigenetics and its role in ageing and cancer Abhimanyu K. Jha*, Shailesh Kumar*, Mohsen Nikbakht, Vishal Sharma, Jagdeep Kaur § Department of Biotechnology, Panjab University, Chandigarh, India *These authors contributed equally to this work Accepted 21 March 2011 Epigenetics refers to the change in gene expression without the change in the sequence of the gene. Epigenetics includes alternate phenotypic states that are not based on differences in genotype, but are generally stably maintained during cell division and are potentially reversible. A much more expanded view of epigenetics involves multiple mechanisms interacting to collectively establish alternate states of chromatin structure, histone modification, associated protein composition and transcriptional activity. Chromatin structure is not fixed. Instead, chromatin is a dynamic identity and is subject to extensive developmental, environmental and age-associated remodeling. In some cases, this remodeling appears to counter the ageing and age-associated diseases, such as cancer, and extend organismal lifespan. Advances in our understanding of chromatin structure, histone modification, transcriptional activity, promoter hypermethylation and global hypomethylation resulted in an increasingly integrated and expanded view of epigenetics. The study of epigenetics reveals how patterns of gene expression are passed from one cell to its descendants, how gene expression changes during the differentiation of one cell type into another, and how environmental factors can change the way genes are expressed. There are far-reaching implications of epigenetic research for human biology and diseases, including our understanding of cancer and ageing. Due to these developments, epigenetic therapy is expanding to include combinations of histone deacetylase inhibitors and DNA methyltransferase inhibitors. This review encompasses the different types of epigenetic changes, the interplay among them and the implications of these epigenetic changes in relation to cancer and ageing. Besides this, the development and perspective of epigenetic therapy has also been discussed in brief. Keywords: Epigenetics, histone deacetylase inhibitors, DNA methyltransferase inhibitors, cancer, histone modification, promoter hypermethylation. INTRODUCTION The central dogma of molecular biology states that the information embedded in the linear nucleotide sequence of DNA contains coding information for RNA and protein, as well as regulatory sequences that control the biology of DNA itself. The word "epigenetics" was coined by the developmental biologist C. H. Waddington in 1942 (Waddington et al., 1942) The Greek prefix "epi-" in the word "epigenetics" implies features that are "on top of" or "in addition to" genetics. Waddington proposed the epigenetic model to describe, the interaction of genes within a multicellular organism with their surroundings to produce a particular phenotype and this hypothesis was known as Conrad hypothesis. Holliday and Pugh proposed in 1975 that covalent chemical DNA § Corresponding author Email: jagsekhon@yahoo.com modifications, including methylation of cytosine-guanine (CpG) dinucleotides, were the molecular mechanisms behind Conrad’s hypothesis. Because all cells within an organism inherit the same DNA sequences, the process of cellular differentiation depend on pattern of epigenetic rather than genetic inheritance. Robin Holliday defined epigenetics as "the study of the mechanisms of temporal and spatial control of gene activity during the development of complex organisms" (Holliday et al.,1996). Thus, the word "epigenetic" can be used to describe any aspect other than DNA sequence that influences the development of an organism. The modern usage of the word "epigenetics" usually refers to heritable traits that do not involve changes to the underlying DNA sequence. Epigenetic regulation mediates adaptation to the environment by the genome lending plasticity that