A bridge between sirtuins and Werner’s

Because every longevity-control gene eventually is eventually shown to interact with every other longevity-control gene, it is perhaps not surprising that SIRT1 deacetylates WRN, the protein whose gene is mutated in the devastating human progeria Werner’s Syndrome. Both the helicase and exonuclease activities of the WRN protein are more active in the deacetylated state; thus, the longevity-assurance gene (SIRT1) is responsible for boosting the activity of the major player in the cellular response to DNA damage (WRN), which is the way we’d expect it to work.

Two other recent reports describing progress on WRN reveal that the protein plays a significant role in DNA metabolism under normal growth and after DNA damage: WRN is required both for replication fork progression after genotoxic stress as well as suppressing the spontaneous formation of telomeric DNA circles. These latter structures (which remind me of the extrachromosomal ribosomal DNA circles from the early years of the sirtuin field) are associated with both telomere shortening and cellular senescence.

Advertisements

3 comments

  1. I was wondering when you would write about the SIRT1/WRN paper 😉
    The paper about WRN and telomeric circles was new to me, and lies on top of my reading stack now. Thanks!

  2. Yeah…I always have a giant backlog. Sometimes I wish I had a staff. Certainly, I no longer make fun of SAGE-KE for going out of business; I now understand why they needed money and full-time writers. This literature is…huge.

  3. Aging Not Approachable With Oversimplification
    The Aging Chain
    Aging genes age genomes age cells age cellular organisms And Vice Versa

    A. “Sirtuin shown to control gene activity”
    http://www.sciencenews.org/view/generic/id/39788/title/Sirtuin_shown_to_control_gene_activity_
    A previously overlooked protein called SIRT6 provides some molecular clues to aging.

    Chua’s and Chang’s groups together show that SIRT6 works with a master regulatory complex called NFkappa-B to govern activity of genes associated with aging, inflammation, immunity and metabolism. When SIRT6 is missing, NFkappa-B becomes hyperactive and turns up activity of aging-linked genes.

    Mostoslavsky believes many important body systems are affected by SIRT6, but cautions that the enzyme is not necessarily an anti-aging protein. The mutant mice lacking the protein have severe metabolic disturbances that could account for premature aging. Researchers have not yet detected any change in SIRT6 levels or activity with age.

    “Whether this has a role in the normal aging process, we still don’t have enough information to answer that,” he says.

    B. Aging, lifetime and age

    Aging = to become old, show the effects or the characteristics of increasing age, the increasing liferime. Thee effects and characteristics of not only the totality of the system but also of each and every component and components of the components of the system. The system is the totality of the components.

    lifetime = the duration of the existence of a living being, an organism, or an inanimate thing, a material, star or subatomic particle.

    age = the length of an existence extending from the beginning to any given time.

    Dov Henis

    (Comments From The 22nd Century)
    http://blog.360.yahoo.com/blog-P81pQcU1dLBbHgtjQjxG_Q–?cq=1

    Life’s Manifest
    http://www.the-scientist.com/community/posts/list/112.page#578

Comments are closed.