• Cellular rejuvenation therapy safely rev

    From ScienceDaily@1:317/3 to All on Monday, March 07, 2022 21:30:48
    Cellular rejuvenation therapy safely reverses signs of aging in mice


    Date:
    March 7, 2022
    Source:
    Salk Institute
    Summary:
    Age may be just a number, but it's a number that often carries
    unwanted side effects, from brittle bones and weaker muscles
    to increased risks of cardiovascular disease and cancer. Now,
    scientists have shown that they can safely and effectively reverse
    the aging process in middle-aged and elderly mice by partially
    resetting their cells to more youthful states.



    FULL STORY ==========================================================================
    Age may be just a number, but it's a number that often carries unwanted
    side effects, from brittle bones and weaker muscles to increased risks of cardiovascular disease and cancer. Now, scientists at the Salk Institute,
    in collaboration with Genentech, a member of the Roche group, have
    shown that they can safely and effectively reverse the aging process in middle-aged and elderly mice by partially resetting their cells to more youthful states.


    ==========================================================================
    "We are elated that we can use this approach across the life span to slow
    down aging in normal animals. The technique is both safe and effective
    in mice," says Juan Carlos Izpisua Belmonte, co-corresponding author
    and a professor in Salk's Gene Expression Laboratory. "In addition to
    tackling age-related diseases, this approach may provide the biomedical community with a new tool to restore tissue and organismal health by
    improving cell function and resilience in different disease situations,
    such as neurodegenerative diseases." As organisms age, it is not
    just their outward appearances and health that change; every cell
    in their bodies carries a molecular clock that records the passage
    of time. Cells isolated from older people or animals have different
    patterns of chemicals along their DNA -- called epigenetic markers --
    compared to younger people or animals. Scientists know that adding a
    mixture of four reprogramming molecules -- Oct4, Sox2, Klf4 and cMyc,
    also known as "Yamanaka factors" -- to cells can reset these epigenetic
    marks to their original patterns. This approach is how researchers can
    dial back adult cells, developmentally speaking, into stem cells.

    In 2016, Izpisua Belmonte's lab reported for the first time that they
    could use the Yamanaka factors to counter the signs of aging and increase
    life span in mice with a premature aging disease. More recently, the
    team found that, even in young mice, the Yamanaka factors can accelerate
    muscle regeneration.

    Following these initial observations, other scientists have used the
    same approach to improve the function of other tissues like the heart,
    brain and optic nerve, which is involved in vision.

    In the new study, Izpisua Belmonte and his colleagues tested variations of
    the cellular rejuvenation approach in healthy animals as they aged. One
    group of mice received regular doses of the Yamanaka factors from the
    time they were 15 months old until 22 months, approximately equivalent to
    age 50 through 70 in humans. Another group was treated from 12 through
    22 months, approximately age 35 to 70 in humans. And a third group was
    treated for just one month at age 25 months, similar to age 80 in humans.

    "What we really wanted to establish was that using this approach for a
    longer time span is safe," says Pradeep Reddy, a Salk staff scientist and co-first author of the new paper. "Indeed, we did not see any negative
    effects on the health, behavior or body weight of these animals."
    Compared to control animals, there were no blood cell alterations or neurological changes in the mice that had received the Yamanaka factors.

    Moreover, the team found no cancers in any of the groups of animals.



    ==========================================================================
    When the researchers looked at normal signs of aging in the animals that
    had undergone the treatment, they found that the mice, in many ways,
    resembled younger animals. In both the kidneys and skin, the epigenetics
    of treated animals more closely resembled epigenetic patterns seen in
    younger animals.

    When injured, the skin cells of treated animals had a greater ability to proliferate and were less likely to form permanent scars -- older animals usually show less skin cell proliferation and more scarring. Moreover, metabolic molecules in the blood of treated animals did not show normal
    age- related changes.

    This youthfulness was observed in the animals treated for seven or 10
    months with the Yamanaka factors, but not the animals treated for just
    one month.

    What's more, when the treated animals were analyzed midway through their treatment, the effects were not yet as evident. This suggests that the treatment is not simply pausing aging, but actively turning it backwards -
    - although more research is needed to differentiate between the two.

    The team is now planning future research to analyze how specific
    molecules and genes are changed by long-term treatment with the Yamanaka factors. They are also developing new ways of delivering the factors.

    "At the end of the day, we want to bring resilience and function back
    to older cells so that they are more resistant to stress, injury and
    disease," says Reddy. "This study shows that, at least in mice, there's
    a path forward to achieving that." Belmonte is currently an Institute
    Director at Altos Labs, Inc., in addition to being a professor at the
    Salk Institute.

    Other authors included Mako Yamamoto, Isabel Guillen Guillen, Sanjeeb
    Sahu, Chao Wang, Yosu Luque, Javier Prieto, Lei Shi, Kensaku Shojima,
    Tomoaki Hishida and Concepcion Rodriguez Esteban of Salk; Kristen
    Browder, Zijuan Lai, Qingling Li, Feroza Choudhury, Weng Wong, Yuxin
    Liang, Dewakar Sangaraju, Wendy Sandoval, Michal Pawlak, Jason Vander
    Heiden and Heinrich Jasper of Genentech, Inc.; Amin Haghani and Steve
    Horvath of UCLA; Estrella Nun~ez Delicado of Universidad Cato'lica San
    Antonio de Murcia; and Pedro Guillen Garcia of Cli'nica CEMTRO.

    The study was supported by Universidad Cato'lica San Antonio de Murcia
    (UCAM), and Fundacio'n Dr. Pedro Guille'n.

    Video: https://youtu.be/XryS6SnGTho ========================================================================== Story Source: Materials provided by Salk_Institute. Note: Content may
    be edited for style and length.


    ========================================================================== Journal Reference:
    1. Browder, K.C., Reddy, P., Yamamoto, M. et al. In vivo partial
    reprogramming alters age-associated molecular changes
    during physiological aging in mice. Nat Aging, 2022 DOI:
    10.1038/s43587-022- 00183-2 ==========================================================================

    Link to news story: https://www.sciencedaily.com/releases/2022/03/220307113027.htm

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