Investigating Epigenetic Drift in Aging

Epigenetics is the study of dynamic alterations to DNA that affect the rate at which specific proteins are generated from its blueprint, but do not change the blueprint itself. One example is DNA methylation, the decoration of DNA with methyl groups. Patterns of DNA methylation change with advancing age, and some of those changes are similar enough between individuals to be used as a measure of age.

Why do epigenetic patterns change with aging? The obvious suggestion, though at this point it remains a challenge to drawn direct lines from cause to effect, is that it is a reaction to rising levels of the cellular and molecular damage that causes degenerative aging. The same forms of damage occur in everyone, so reactions to that damage should be similar in everyone. Epigenetic changes occur in reaction to other environmental circumstances, so it shouldn't be surprising to find them happening in response to the damage of aging.

Two well-known features of aging are the gradual decline of the body's ability to regenerate tissues, as well as an increased incidence of diseases like cancer and Alzheimers. One of the most recent exciting findings which may underlie the aging process is a gradual modification of DNA, called epigenetic drift, which is effected by the covalent addition and removal of methyl groups, which in turn can deregulate the activity of nearby genes. However, this study presents the most convincing evidence to date that epigenetic drift acts to stabilize the activity levels of nearby genes.

This study shows that instead, epigenetic drift may act primarly to disrupt DNA binding patterns of proteins which regulate the activity of many genes, and moreover identifies specific regulatory proteins with key roles in cancer and Alzheimers. The study also performs the most comprehensive analysis of epigenetic drift at different spatial scales, demonstrating that epigenetic drift on the largest length scales is highly reminiscent of those seen in cancer. In summary, this work substantially supports the view that epigenetic drift may contribute to the age-associated increased risk of diseases like cancer and Alzheimers, by disrupting master regulators of genomewide gene activity.

Link: http://dx.doi.org/10.1371/journal.pgen.1004996

Comments

Possibly a result of ROS, environemntal damage and importantly Telomere attrition which changes gene expression via TPE and TPE-OLD this then feeds back and Epigentic changes occur via histones and Mythelation patterns, this then feeds back shortening telomeres more and the downward spiral begins.

Restoration of the Epigentic pattern to a younger configuration could possibly reverse this situation. Parabiosis studies have shown it is possble to restore a younger phenotype which is likely due to factoral reprogramming of Epigenetic patterns.

Perhaps sufficient exposure to a young mileau could potentially restore the Endocrine system which would then resume expression of youthful factors on its own.

It would be very easy to test this as the technology is available now and even FDA approved for safety.

Posted by: Steve H at March 30th, 2015 5:03 AM

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