{"id":301,"date":"2014-10-29T21:50:33","date_gmt":"2014-10-29T21:50:33","guid":{"rendered":"http:\/\/joshmitteldorf.peachpuff-wolverine-566518.hostingersite.com\/?p=301"},"modified":"2014-10-30T02:55:35","modified_gmt":"2014-10-30T02:55:35","slug":"open-letter-on-research-priorities-in-aging","status":"publish","type":"post","link":"https:\/\/scienceblog.com\/joshmitteldorf\/2014\/10\/29\/open-letter-on-research-priorities-in-aging\/","title":{"rendered":"Open Letter on Research Priorities in Aging"},"content":{"rendered":"

Last week, I had the honor of speaking with Cynthia Kenyon, who has been recruited by Google to direct research activities at their new venture into aging medicine, called CALICO, for California Life Co. \u00a0She was kind enough to listen to my thoughts on research priorities seeking near-term breakthroughs in human life extension. \u00a0Here is what I said to her, paraphrased with some added background and comments.<\/i><\/p>\n

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It is my belief that the timing of development and aging is determined by chromatin* state. \u00a0The body knows how to be young, and it knows how to be old. \u00a0The difference is coded in chromosomes, especially in telomere length of stem cells and epigenetic markers in endocrine cells.<\/p>\n

*<\/b> Chromatin is the DNA in the cell nucleus, together with the histone spools around which it is wrapped and all the proteins and side-groups that are loosely and temporarily attached. \u00a0Spooled DNA is called \u201cheterochromatin\u201d and it is mostly silent. \u00a0Unspooled DNA is termed \u201ceuchromatin\u201d and it is more likely to be active. \u00a0All the protein markers, the methyl groups and acetyl groups strategically placed, together determine when and where particular genes are expressed. \u00a0This phenomenon is called \u201cepigenetics\u201d. \u00a0How is epigenetic programming effected? \u00a0The cell\u2019s epigenetic language if much more complex than the Genetic Code, and is yet poorly understood.<\/p>\n

I am proposing that aging is, in large part, a matter of epigenetics. \u00a0A different set of genes is turned on when we are young compared to when we are old, and that makes all the difference.<\/i><\/b> \u00a0<\/b>Here are four references on the subject, including my own #4 [Ref1<\/a>, Ref2<\/a>, Ref3<\/a>, Ref4<\/a>].<\/p>\n

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Background assumptions<\/b><\/p>\n

I believe that aging is controlled by several biological clocks. \u00a0This is a strong claim, but I think it has good support, outlined\u00a0in the references above. \u00a0Biological clocks certainly control development, puberty and related schedules early in life. \u00a0How the body knows its own age is yet incompletely understood. \u00a0It\u2019s a good bet that the same clocks that control development have been re-purposed to control aging.<\/p>\n

There are three clocks we know something about. \u00a0These are the epigenetic clock, cellular senescence (telomere loss), and life-long shrinkage of the thymus<\/a>, master gland of the immune system.<\/p>\n

A common way to construct a clock is with a feedback loop. \u00a0A clock looks at itself to determine its next move. \u00a0The body has a feedback loop between epigenetic state (at a cell level) and circulating hormones and RNAs (at a systemic level).<\/p>\n