Scientists discover key driver of human aging — Findings on premature aging syndrome could lead to way of slowing or reversing aging process

Salk Institute for Biological Studies
News Release
Scientists discover key driver of human aging
Findings on premature aging syndrome could lead to way of slowing or reversing aging process

Some highlights:

  • Salk team was lead by Juan Carlos Izpisua Belmonte
  • Ties the aging process to the deterioration of tightly packaged bundles of cellular DNA
  • Werner syndrome causes people to age faster than normal
  • Genetic mutations underlying Werner syndrome resulted in the deterioration of bundles of DNA known as heterochromatin
  • Belmonte says “This has implications beyond Werner syndrome, as it identifies a central mechanism of aging–heterochromatin disorganization–which has been shown to be reversible.”
  • Discovery made possible through a combination of cutting-edge stem cell and gene-editing technologies
  • Werner syndrome is caused by a mutation to the RecQ helicase-like gene (WRN) which generates the WRN protein.
    • Normal form of the protein is an enzyme that maintains DNA structure and integrity.
    • Mutated Werner syndrome protein disrupts replication and repair of DNA and the expression of genes, which was thought to cause premature aging.
  • Salk scientists sought to determine precisely how the mutated WRN protein causes so much cellular mayhem
    • They created an unprecedented cellular model of Werner syndrome by using a cutting-edge gene-editing technology to delete WRN gene in human stem cells
    • Resulting cells mimicked the genetic mutation seen in actual Werner syndrome patients, so the cells began to age more rapidly than normal.
    • Deletion of the WRN gene also led to disruptions to the structure of heterochromatin, the tightly packed DNA found in a cell’s nucleus.
    • So the WRN protein helps maintain heterochromatin
  • Researchers showed that the protein interacts directly with molecular structures known to stabilize heterochromatin–revealing a kind of smoking gun that, for the first time, directly links mutated WRN protein to heterochromatin destabilization.
  • Izpisua Belmonte added that more extensive studies will be needed, including how it interacts with other cellular processes implicated in aging, such as telomere shortening.

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Final point for aging solutions:

  • Belmonte team is developing epigenetic editing technologies to reverse epigenetic alterations with a role in human aging and disease.

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Article:
http://www.salk.edu/news/pressrelease_details.php?press_id=2080

Johnny


GRG Member Harold Katcher sent the following useful information:

That disorganization of heterochromatin is a downstream process. Think that the helicase is either down-regulated with age or miRNAs against it are up-regulated or both or some other life-stage-dependent mechanism prevents chromatin repair and remodeling.  So in the case of Werner’s syndrome, the helicase gene is constitutionally lost or impaired at age zero, in non-Werner’s folks (us), it becomes reduced in effect with age, thus allowing a longer lifespan. But it is one of many aging clocks I believe, the telomeres are another, mitochondrial dysfunction….

So the question is, since we know that genes are not randomly activate/inactivated at different life-stages  (as opposed to the ‘wear and tear’ers who believe that randomly inactivated essential genes for repair and maintenance  produces aging  (while no other genes are apparently ‘randomly’ inactivated), that position sounds so dubious as to make me feel embarrassed for the majority of scientists in aging research), the question is what inactivated those repair and maintenance genes?  Is it a cell-intrinsic process or is it signalling from body to cell? I’d bet on the latter.

Sincerely,
Harold Katcher


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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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