Werner Syndrome – another model for aging

My last major post traced developments related to a form of progeria (premature aging) known as Hutchinson-Gilford progeria syndrome, or HGPS, for short.  The discussion and comments on this post are leading us down new paths, such as exploring the role of progerin and FTI therapies and seemingly away from the usual theories of aging.  There is also a different rare form of progeria known as Werner Syndrome (WS) that is worth looking at for what it might tell us about normal aging.

WS, sometimes called adult progeria, is characterized by the premature onset of age-related diseases, including inflammatory diseases, atherosclerosis and cancer.  People with WS may develop the symptoms of very old age by the time they turn 30 or 40, including “wrinkled skin, baldness, cataracts, muscular atrophy and a tendency to diabetes mellitus, among others(ref).”  Cells from people with WS when cultured have shorter life spans than cells from normal people.  “In culture, cells obtained from patients with WS are genetically unstable, characterized by an increased frequency of nonclonal translocations and extensive DNA deletions(ref).”  It has recently been shown that WS is due to a mutation in a gene called WRN.  It is a hellicase deficiency disease.  Hellicases are enzymes important for many cellular processes including “DNA replication, transcription, translation, recombination, DNA repair, and ribosome biogenesis.”  Normally, the WRN gene “ functions as a key factor in resolving aberrant DNA structures that arise from DNA metabolic processes such as replication, recombination and/or repair, to preserve the genetic integrity in cells(ref).”

Unlike the case for HGPS, there appears to be a direct link between the aging mechanisms operating in WS patients and at least one of the usual theories of aging, the telomere shortning and damage theory. For example, regarding study of a mouse model of WS the authors write “Recent studies of the telomerase-Werner double null mouse link telomere dysfunction to accelerated aging and tumorigenesis in the setting of Werner deficiency. This mouse model thus provides a unique genetic platform to explore molecular mechanisms by which telomere dysfunction and loss of WRN gene function leads to the onset of premature aging and cancer(ref).”  Some researchers highlight the roles of cell senescence and telomeres in WS: “Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts(ref).”  Normal hellicase structures can be very important for assuring normal telomere structures(ref), a situation not present in WS.  Other researchers believe WS operates primarily through other than telomere erosion or damage:  “–  our data suggest that the abbreviated replicative life span of WS cells is due to a stress-induced, p38-mediated growth arrest that is independent of telomere erosion(ref).”

Looking for bridges between the genetic mechanisms operating in HGPS and those operating in WS:  1  It is easy to find commonality of end-results, specifically premature aging phenotypes like baldness, wrinkled skin and cardiovascular disease, and 2.  The underlying genomic mechanisms themselves are in the first instance quite different; they involve activation of different genes and the actions of different protein products. I do not see any easy “Ah hah, here is the common mechanism of aging involved in HGPS, WS and normal aging.   Both HGPS and WS suggest means by which normal aging might work and possibly be slowed down, having to do with accumulation of progerin and possible treatment with FTIs in the case of HGPS, and having to do with P38, telomere shortening and telomerase activation in the case of WS.

About Vince Giuliano

Being a follower, connoisseur, and interpreter of longevity research is my latest career, since 2007. I believe I am unique among the researchers and writers in the aging sciences community in one critical respect. That is, I personally practice the anti-aging interventions that I preach and that has kept me healthy, young, active and highly involved at my age, now 93. I am as productive as I was at age 45. I don’t know of anybody else active in that community in my age bracket. In particular, I have focused on the importance of controlling chronic inflammation for healthy aging, and have written a number of articles on that subject in this blog. In 2014, I created a dietary supplement to further this objective. In 2019, two family colleagues and I started up Synergy Bioherbals, a dietary supplement company that is now selling this product. In earlier reincarnations of my career. I was Founding Dean of a graduate school and a full 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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2 Responses to Werner Syndrome – another model for aging

  1. Res says:

    Another progeria disease Cockayne syndrome has a drug now called prodarsan


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