Epigenetics, Epigenomics and Aging

Human traits and gene expression are affected by signals that can result from interaction with our environment, including what a mother eats and the social conditioning received by a young child.  Imagine a control system of biomolecular switches that can turn expression of genes on or off.  And imagine that those switches can be controlled by what we eat, do or experience in any way or even think.  Further imagine that the positions of those switches, genes being turned on or off, can be inherited.  If you can imagine those things you have imagined the science called Epigenetics.  Epigenetics and epigenomics are concerned with the study of changes in the regulation of gene activity and expression that are not dependent on gene sequence in DNA.  The subjects are a bit dense but are of considerable and growing importance for disease and aging research.  Here is a primer:

Epigenetics may be concerned with both heritable and non-heritable changes in gene activity and expression and also stable, long-term alterations in the gene transcriptional potential of a cell.  While epigenetics refers to the study of single genes or sets of genes, epigenomics refers to more global analyses of epigenetic changes across the entire genome(ref). 

Events in the early development of an organism can affect the phenotype (observable characteristics and traits) creating biological changes in the epigenome (the overall epigenetic state of a cell or organism).   This is a way of saying that genes by themselves do not determine our destinies or the diseases we get or the way we age.  Simply put, there is a lot more going on in a higher organism than can be explained by genetics.  Humans physical traits are determined not only by what is in our genes but also by factors that affect gene expression and changes in gene regulation such as are evident in the growth of an embryo or in differentiation of stem cells.  For example, what are the factors that allow a single fertilized human egg to continue dividing into all of the specialized cell types and organs – blood cells, neurons, bone cells, muscle cells, etc.?  That information is both genomic and epigenomic information not provided just by the sequence of genes in a strand of DNA.  Aging itself appears to be an epigenomic phenomenon, with the typical pattern of gene expression changing in the course of a lifetime. 

Like protein folding, a subject I discussed recently, epigenomics is a frontier area where little is yet known compared to what is yet to be learned and where there is a lot of excitement.  It is starting to change the ways we look at many things in biology and medicine.  There is increasing agreement that truly understanding diseases and susceptibilities to diseases is a matter of both genetics and epigenetics seen in the context of environment – and that goes for cancers, neurological and cardiovascular disorders, psychiatric disorders as well as virtually all other diseases.

One area where epigenomic effects are evident is the case of monozygotic twins.  Despite being genetically identical they can be very different in their phenotypes and susceptibilities to many diseases, such as diabetes, schizophrenia and Huntington’s disease and can weigh different amounts even when fed the same diet.  Some of these characteristics may be inherited.  In one experiment at Duke University, two genetically identical mother mice were fed different diets, one a normal diet, the other a diet enriched with choline, betaine, folic acid and vitamin B-12.  The offspring mice looked and were very different.  For one thing the offsprings of the normally fed mice had white hair while the offsprings of the supplemented mother had rich brown hair.  The differences were epigenomic.  Despite genetic identity, the physical characteristics of the offsprings depended on the environment and behavior of the mothers. The implications of this little experiment and similar ones are staggering for those of us concerned with dietary supplementation.  Dietary supplementation of parents can result in their offsprings having an altered biochemical makeup and altered physical characteristics.  And a corollary is that dietary supplementation can cause permanent as well as temporary changes in ourselves as well.  I will probably take 50 to 100 years before we will know for sure which dietary supplements create what results in our offsprings, and in the meantime we will have to play it by ear or depend on animal studies which are yet to be conducted.

Genetic imprinting is a process that has been known for some time.  For certain genes, either the mother’s version or the father’s version is selected by an offspring.  This process of selection can profoundly affect disease susceptibility and is now believed to be epigenetically controlled instead of a random one. For example the imprinted KCNK9 potassium channel gene is frequently over-expressed in breast cancers.  Some researchers believe that our ability to diagnose and treat many diseases that have a genetic origin will depend on our identifying the human imprinted genes and determining how they are epigenetically regulated.

One area of epigenomic research is looking for where and how epigenomic information is stored in humans.  The study involves both experimental and computational approaches.  Methylation (the chemical replacement of a hydrogen atom with a methyl group) of  DNA on chromosomes is one of the important encoding mechanisms.  A number of projects have been concerned with mapping the methylation landscape of the human genome, commencing with the Human Epigenome Project that was started in 2000.  The Human Epigenome Pilot Project has “  — recently completed a pilot study of the methylation patterns within the Major Histocompatibility Complex (MHC) – a region of chromosome 6 that is associated with more diseases than any other region in the human genome.”  They believe the project will provide unprecedented insight, particularly applicable to autoimmune diseases. A 5-year initiative involving four research centers was funded recently called the NH Epigenome Roadmap and plans to study 100 cell types, and there are a number of other epigenomic study initiatives. New fast sequencers allow rapid analysis of methylation profiles but the challenge is very complex because diseases may correspond to alterations in both genomic and methylation profiles.  Much is being learned but there is very much more yet to be learned.   

Already, certain DNA methylation changes are known to be associated with aging and others associated with certain diseases like lupus and scleroderma.   It is possible that yet-another theory of aging could be added to my Anti-Aging Firewalls treatise at some point called Changes in DNA methylation profiles.

The impact of epigenetic knowledge is expected to be felt across the board in medicine, including in psychiatry.  Stress and aggression are known to induce epigenetic changes in mice, and addiction does too.  Cocaine exposure, for example, is known to create epigenetic changes in specific areas in the brain. How a mother treats her small daughter may generate epigenomic changes that condition how that girl behaves throughout the rest of her life, and also condition the behavior of her daughter’s daughter.

Epigenomics provides a layer of information applicable to diseases and aging beyond that available in genomics, but there are yet-other layers to consider including proteomics (understanding structures and functions of proteins including factors such as folding) and transcriptomics (understanding the set of all messenger RNA molecules, or “transcripts,” produced in one or a population of cells).  The hope is that by mastering genomics, epigenomics, proteomics and transcriptomics and how they work together in specific instances we will gain mastery over all diseases and the process of aging.  We have a ways to go.

If you have a background in molecular biology and genetics, a more technical discussion of epigenetics can be found here. 

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career. I have been at this part-time for well over a decade, and in 2007 this became my mainline activity. In earlier reincarnations of my career. I was founding dean of a graduate school and a university professor at the State University of New York, a senior consultant working in a variety of fields at Arthur D. Little, Inc., Chief Scientist and C00 of Mirror Systems, a software company, and an international Internet consultant. I got off the ground with one of the earliest PhD's from Harvard in a field later to become known as computer science. Because there was no academic field of computer science at the time, to get through I had to qualify myself in hard sciences, so my studies focused heavily on quantum physics. In various ways I contributed to the Computer Revolution starting in the 1950s and the Internet Revolution starting in the late 1980s. I am now engaged in doing the same for The Longevity Revolution. I have published something like 200 books and papers as well as over 430 substantive.entries in this blog, and have enjoyed various periods of notoriety. If you do a Google search on Vincent E. Giuliano, most if not all of the entries on the first few pages that come up will be ones relating to me. I have a general writings site at www.vincegiuliano.com and an extensive site of my art at www.giulianoart.com. Please note that I have recently changed my mailbox to vegiuliano@agingsciences.com.
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  1. Pingback: Homicide by DNA methylation | AGING SCIENCES – Anti-Aging Firewalls

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