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Yet More Mapping of Age-Related Epigenetic Changes


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Posted 26 November 2015 - 02:12 PM


Epigenetic changes occur constantly, altering the production of proteins in response to circumstances, and thus changing cell and tissue behavior. Some of these changes occur in reaction to the cell and tissue damage of aging, and are characteristic enough to allow development of a measure of biological age, an assessment of how damaged an individual is. This is a work in progress, but a good, cheap measure of biological age is a needed tool in the field of longevity science. Currently the only way to establish that potential rejuvenation treatment works in the sense of extending healthy life is to wait and see what it does to life expectancy, which makes exploration of ideas prohibitively expensive, and slows progress across the whole field:

To examine the changes that occur in blood as an individual ages, researchers conducted an extensive study using thousands of patient blood samples. In a remarkable show of replication, the study was initially performed with blood samples from individuals of European ancestry and then replicated in additional European ancestry samples, totaling an amazing 14,983 individual European ancestry samples. The study was then extended to various ethnic groups, including samples from individuals of Hispanic, African, or Native American ancestry. The study identified 1,497 genes in blood cells and/or brain tissue that showed significantly differential expression patterns in older individuals when compared to younger individuals.

There were three distinct groups of genes that were negatively correlated with chronological age. The first group included three subgroups: ribosomal genes (factories on which a RNA is translated into a protein), mitochondrial genes (energy factories of the cells), and genes associated with DNA replication and repair (DNA maintenance and fidelity). All of the genes associated with these subgroups are vitally important to the health of a cell and tissue. The second large group consisted of genes associated with immunity. The third large group was composed of genes that code for the actual ribosomal subunits. Decreased gene expression could help explain the decreased "health" of older cells and increased mutation rates in older cells. There were also four groups of genes positively correlated with age, which were focused on cellular structure, immunity, fatty acid metabolism, and lysosome activity.

Another interesting finding in this study involved epigenetic patterns, specifically methylation on cytosines (one of the four nucleotide bases in DNA). This study showed that those genes whose expression pattern changed with age were highly enriched for the presence of regulatory cytosines. This could indicate how gene expression is controlled as the individual ages. There are several targeted methylation therapies in development that might potentially offer the ability to effectively and safely alter these methylation patterns for therapeutic purposes. The authors found that by combining the transcriptomic expression patterns and the epigenetic patterns a "chronological" age predictor could be used to better understand an individual's "age" in terms of health. Further refinement is needed, but this type of predictor could have a substantial impact on prediction, diagnosis and treatment of individuals, perhaps even allowing for preventive treatments before symptoms progress to disease level changes.

Link: http://sage.buckinst...-in-your-blood/


View the full article at FightAging




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