Salk Institute for Biological Studies
Scientists discover key driver of human aging
Findings on premature aging syndrome could lead to way of slowing or reversing aging process
- 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.
Final point for aging solutions:
- Belmonte team is developing epigenetic editing technologies to reverse epigenetic alterations with a role in human aging and disease.
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.
*** CLICK HERE to Support — and Benefit From — Aging Solutions ***
CLICK HERE for the Main Foundation Web Site: Carl I. Bourhenne Medical Research Foundation / Aging Intervention Foundation
About Me: Johnny Adams
Call Johnny at (650) 265-4969 or (949) 922-9786 cell
Email: JAdams – at – AgingIntervention .org