Cocktail Yamanaki extended the life of mice by 50%



    This is a photo of LAKI 4F mice with Yamanaki factors with and without doxycycline, as well as long-lived WT mice with doxycycline (antibiotic) and Yamanaki factors. Look at the curve of the spine.

    LAKI are fast-growing mice with a mutation in lamin A (LMNA). Long-lived mice put the same experience, but they are now only 12 months, so with an average lifespan of 3 years and a maximum of 5 years today, the results can be expected in 2018-2019.

    The article itself is in Cell . For those who do not have access - use sci-hub.io - pirated scientific articles.

    The experiment was conducted at the Salk Institute in La Hall, Southern California by the Spaniard Balmonte.
    It all started in 2006, when the Japanese Yamanaki discovered 24 factors (now only 4 OSKM are the main factors with which the experiment was carried out) of cell de-differentiation or cell pluripotency by cell circulation, for example, skin, back into stem cells.

    Then, in 2013, German Croats found 353 epigenetic markers of human aging , which were used to determine the chronological age of a person with an accuracy of 1.5 years. For stem cells, this age was 0.

    For those who are interested: a recent scientist at Harvard and Moscow University Vadim Gladyshev , who received a megagrant, identified the same epigenetic biomarkers of the biological age of a mouse - fightaging blog says about this . This is very important for the accelerated development of new therapies or geroprotectors in mice.

    And a small insider for dessert. Now Calicoconducts experience on 1000 mice at Stanford Jackson Lab divided into two groups - ordinary long-lived mice and the same mice but on a hungry diet, prolonging the life of mice by a record 50% (and only 5% according to the latest data on primates). When the experience ends this way, Google’s spinoff hopes to establish biomarkers of mouse biological age that are needed to accelerate the development of therapies or geroprotectors (apparently, they take blood tests in the process).

    Another small insider from the article New Yorker Silicon Valley Quest for immortality translated on vc.ru- Ned David 49 from Unity Biotechnology, which received an investment of $ 116 million, mainly to fight sensational cells, last year went to Balmont in December twice and one in March - they are planning new experiments (with the budget of the entire Salk institute only 117 million, so a startup for a radical extension of life here is very useful).

    So it turned out that the zeroing process is not binary (either stem or not), but quite a gradual process. And if you don’t bother with a dose of Yamanaki’s cocktail in a cage, and give it only a sip of it, then the epigenetic markers are not zeroed, but only rolled back. The cell does not change its phenotype, and so it remains with the skin or heart cells (that is, unlike the pluripotent one, it does not express the Nanog marker - this is for botans).

    Thus, Balmonte rolled back the epigenetic clock of mice that had Yamanaki cassettes in the genome, which were activated by doxycycline and extended the life of the mice to a maximum of 33% and by 50% in the median.

    If laboratory mice drank water with doxycycline — but only two days a week — they lived more than thirty percent longer. In wild mice (only 12 months old) subjected to the same treatments, the muscles and pancreas were renewed.



    Slides of the speech of Yuri Deigin on the Scientific Environment in the Library. Brothers Grimm. Novovagankovsky lane 22.



    This is a graph of the survival of LAKI 4F mice without Yamanaki factors and with Yamanaki factors, without doxycycline, with doxycycline.

    Decreased the critical markers of aging:

    - senescent cells markers and beta p16Ink4a galaktodiaza
    - a marker of DNA double-strand breaks-H2AX gamma
    - an anti-marker protein p53
    - mettaloproteazy
    - interleukin-6
    - mitochondrial reactive oxygen species
    - lengthened telomeres (from the experience of M. Blasco staged in Barcelona the same LAKI)

    Let me remind you that Balmonte did not experience the most optimal way (but experience is the son of difficult mistakes) - he developed a transgenic line of mice with the Yamanaki OSKM genes, which included transcription of these genes when taking doxycycline (antibiotic) twice a week after which they rested for 5 days .

    As can be seen from the graph below, if doxycycline is given not for 2, but for 3 days, then the mice are already starting to breathe, with half of them dying on the 5th day of therapy:



    Now it remains to choose the optimal proportions and timing of these factors, as well as the delivery method and dosing regimen which can extend the life of mice much longer.

    Review in simple language about the discovery of Balmonte in the journal Science .

    To conduct this experiment on a person, you need an AAB viral carrier with Yamanaki factors. As Yuri Deigin suggests, one can simplify the experience and make AAB sharpened solely on the hypothalamus (well, either the pineal gland or the pituitary gland) and other modifiers of brain development and aging. It is also promising not to let the body conduct an epigenetic shift at all, but the experience that will prove such a possibility is not yet known.



    In the meantime, the website of the Open Science Foundation's Open Longevity patient organization for life extension has opened
    Clinical trials of geroprotectors are coming, while specialists have suggested a combination of sartans + statins, but the site is indifferent to any therapy, including the reception of such future geroprotectors as magnesium, NAC - N-acetyl-L-cysteine, glycine, ginkgo biloba (GinkGo Leaf)

    It can download blood tests on aging biomarkers selected by specialists.
    Including automatic loading of data on analysis codes of Lab InVitro.

    These data will then indicate your biological age, and there will also be open data with the possibility of cross-comparison and any research on these biomarkers of people from 20 to 70 years.

    Below 7 hour video of lectures from a meeting on November 26 in a tehnoHub Klyuch.Moskva.Trekhgornaya manufactory.



    → The most complete database of geroprotectors for model organisms .
    → Independently, you can pass epigenetic markers and calculate age using the Croatian epigenetic clock .

    Also popular now: