Yet More Mapping of Age-Related Epigenetic Changes

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.buckinstitute.org/age-its-all-in-your-blood/

Comments

It seems awfully complicated. And considering how these changes might be specific to some tissues, the real picture is probably much more complicated. And I just don't see how any of this will prove useful per se.

There are already super-cheap indicators that are meaningful: muscle mass, cognitive function, stem cell activity...

You can also try a therapy and see how it affects ill-health. For example, rejuvenation should "cure" Alzheimer's, heart conditions and so forth. We know how to measure these.

Posted by: Daniel Lemire at November 26th, 2015 10:16 AM

They serve as good evidence to support reversal of aged phenotypes. If I take someone who is say 60 and profile their gene expression then give them my anti aging pill and measure the expression profile again and it shows changes consistent with a significantly more youthful pattern it supports efficacy of that intervention.

The fact that gene expression changes are predictable makes it a reliable marker of changes, the system Steve Horvath uses is probably the best example of a very useful metric to ascertain if something is working on not. This study whilst in itself is not overly interesting it does serve as a template to help us see if an intervention is working, I see this kind of data as far from useless as it gives us a template to work from.

Posted by: Steve H at November 26th, 2015 12:13 PM

I think I read somewhere that 'synthetic endpoints' are now used in some clinical trials. For example the antibodies blocking the cholesterol uptake protein PCSK9 only have to show that they are reducing blood cholesterol levels, not that they are reducing heart attacks.

I think rather than showing healthy life extension, any future SENS style therapies would hopefully be able to use measures of the damage they are trying to remove. For example anti glucosepane therpies could be approved on whether of not they reduce cross linking in collagen from skin biopsies.

Posted by: jim at November 26th, 2015 1:12 PM
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