Anti-aging breakthrough? This one looks authentic

Yes, there are too many reports the last few years of people announcing the end of aging.  But this, I feel, is the first time a drug has been discovered that has the potential to extend our lives by decades, with a few injections.

Background: As we get older, some of our cells become ‘senescent’.  They don’t just fall down on the job; they send signals out to the body which make us old and (especially) promote inflammation, leading to higher rates of cancer, heart disease and AD.  There are very few senescent cells—perhaps one in 10,000.  But they do enormous damage.

A few years ago, Jan van Deursen of Mayo Clinic showed that by killing off the senescent cells in mice, he could make them live 25% longer.  This was done with a drug, but the catch was that the mice were genetically modified.  Each senescent cell had a bomb in it, and all it took was delivering a trigger.  The treatment only worked if the mice were specially prepared (before birth) with this genetic modification.

This was 2011.  University labs  and drug companies around the world took appropriate notice, and they started working on ways to kill senescent cells without harming normal cells that would work in animals (including you and me) who have not been prepared ahead of time with bombs in their senescent cells.

Yesterday, scientists from the Netherlands announced successful deployment of a magic bullet that would kill senescent cells only.  It works in cell cultures, and it works as an injection in mice that have short lifespans.  (They haven’t had time yet to test it in fully normal mice, but in theory, it should.)

It’s a large molecule that you can’t take in a pill, because your digestive system would dismember it.  But it can be injected, and one dose ought to be rejuvenating.  I expect that people will be lining up to try this within a year, and that the injections will turn out to be needed only once in every few years.

My previous article on the subject
Link to Science News article by Mitch Leslie
Research Article

36 thoughts on “Anti-aging breakthrough? This one looks authentic

  1. Note: According to Blagosklonny theory, rapamycin works because it stops production of senescent cells. So removal of senescent cells is perfectly consistent with Blagosklonny theory.
    Few problems: This is injection. To get this injection first needs to be FDA approved.
    Safe and works: my estimation FDA approval: 20 years.
    Second: Cost: You can bet Medicare not covering; cost $50,000.

    I agree looks good and just put in my i-phone diary:
    2037 get senescent cell removal injection.

  2. As PD Mangan asked, how much of the aging phenotype is caused by senescent cells. The answers were given by the latter experiments of Baker with his clever method of killing p16ink4a expressing cells (senescent cells). This resulted in significant improvements in looks and a significant, but fractional, increase in lifespan length, something on the order of 20-25%, and that was in his second, more recent experiments where Baker used mice with a normal lifespan, not the progeroid mice you are commenting on Josh, we were all waiting to see if it worked on normal lifespan mice and it did.
    So while I’m ready to get rid of my senescent cells, and that should improve my quality of life, that is only partial rejuvenation, but of course it would be a huge plus if it works.

    • Most lifespan increases in mice I expect to have less of an effect in humans than mice, CR for example. But I wonder, might we benefit more than mice (as a percentage) with senescent cell removal? I think there is a good chance, given their much higher cancer rates.

    Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
    Scientists unveil a giant leap for anti-aging
    A conserved NAD+ binding pocket that regulates protein-protein interactions during aging
    Scientists Can Reverse DNA Aging In Mice

    Oral Rapamycin After Coronary Bare-Metal Stent Implantation to Prevent Restenosis: The Prospective, Randomized Oral Rapamycin in Argentina (ORAR II) Study
    Between September 2003 and September 2004, 100 patients were randomized to either oral rapamycin (6-mg loading dose given 2.7 h before intervention followed by 3 mg/day for 14 days) plus diltiazem 180 mg/day or no therapy after the implantation of a coronary bare metal stent design. The primary study end point was incidence of angiographic binary restenosis and late loss at nine months. The secondary end points were target lesion revascularization, target vessel revascularization, and incidence of major adverse cardiovascular events at 1 year.
    Angiographic follow-up was completed in 87% of patients. In the rapamycin group, the drug was well tolerated (26% minor side effects) and was maintained in 96% of patients. At 9 months, the in-segment binary restenosis was reduced by 72% (11.6% rapamycin vs. 42.8% no-therapy group, p = 0.001) and the in-stent binary restenosis was reduced by 65% (12% rapamycin vs. 34.6% no-therapy group, p = 0.009). The in-segment late loss was also significantly reduced with oral therapy (0.66 vs. 1.13 mm, respectively; 43% reduction, p < 0.001). At 1 year, patients in the oral rapamycin group also showed a significantly lower incidence of target vessel revascularization (8.3% vs. 38%, respectively, p < 0.001), target lesion revascularization (7.6% vs. 37.2%, respectively, p 2.5 mm, without diabetes, and unsuitable for long-term antiplatelet therapy.

    • In the oral rapamycin arm, patients received a loading dose of 6 mg at 2.71 ± 0.9 h before stent implantation, followed by 3 mg/day for a total of 14 days. Sustained-release diltiazem 180 mg/day was added to the sirolimus regimen to achieve higher sirolimus blood concentrations

      In conclusion, this was the first randomized study using oral rapamycin in patients with de novo lesions treated with coronary bare metal stent therapy. We report a significant reduction of angiographic and clinical parameters of restenosis, suggesting that this treatment may be a cost-effective alternative to drug-eluting stent therapy in a selected group of patients, such as those at moderate risk of restenosis, with a reference vessel size >2.5 mm, without diabetes, and unsuitable for long-term antiplatelet therapy.

  5. Dear Dr. Mitteldorf,

    For the layman who doesn’t have access to this medical treatment, are there are any practical lifestyle changes or supplements that would allow us to remove senescent cells?

  6. I wonder if this rather large molecule crosses the BBB?

    After all, one of the regions we’d like to eliminate senescent cells is in our brains.

    I suppose that it might be injected intrathecally to bypass the BBB.

    • Manipulating the drug and adding a fluorine atom should solve that issue. Think about fluoroquinolones (ciprofloxacin, levaquin etc.). Part of their potency is due to the fact that they are able to cross the BBB. An added fluorine atom also greatly increases permeability into hard-to-penetrate tissue like cartilage. Arthritis is largely due to cell senescence

      But as Alan points out, this will be a highly patented, fully synthetic drug for the 1% in 2037.

          • Mitigated at least for the mitochondria. The paper makes no claims about MitoQ treatment and tendon health. It’s entirely possible your ruptured tendons will have cells just bursting with normally functioning mitochondria.

            Promising, but they need a study that actually looks at long term (simulated or real) tendon durability.

  7. I found this piece on cellular senescence particularly interesting after having read your 4/4/16 article “Politics Drives a Promising Neutraceutical Underground” which displayed a fairly accurate understanding of anatabine.

    Rock Creek Pharmaceutical (RCPIQ), the company that was persuing drug status for anatabine to treat mild to moderate psoriosis, filed for Chapter 7 Bankruptcy when forced to do so from lack of funds. The IP supporting anatabine is now in the hands of the Delaware Bankruptcy Court where it probably will go to the highest bidder. Among that IP is the World Patent WO 2011/119722 A2 ( ) which contains the following from its item (60):

    [60] Anatabine may have a positive effect on telomere length. Thus, in some embodiments anatabine can be administered to reduce and/or reverse cellular senescence {i.e., aging). Conditions associated with cellular senescence can be treated.

  8. Josh, this is break through is fantastic. I wonder if you would share your thoughts on a couple questions.

    – How do you think this will affect. The CellAge research that got funded on
    – Telomeres are known to be ‘self shortening’ if lengthened artificially, do you think eliminating senescent cells would alter the body’s chemistry enough that telos would stay somewhat longer after treatment?

    • The crowd-funded work at is only for $34,000. Now we know there is big money in this field from governments and from Big Pharma. I think the crowd-funded work would be better directed at areas that are not being pursued by the large funders, and there are plenty such.

  9. This is not a break through… if you remove senescent cells, then damages occour even faster and earlier then normal use of tissue…

    • Could you cite your evidence for this?

      Certainly we believe that it might impair wound healing (although children’s wounds seem to heal remarkably fast), but everything else leads us to believe that these senescent cells are detrimental to the organism.

    • Wat? Cells around wounds senesce because damage. Just don’t take your injection right after you’ve been injured and you’ll be fine.

  10. Cell biologist Peter de Keizer of Erasmus University Medical Center in Rotterdam, the Netherlands, and colleagues were investigating how senescent cells stay alive when they uncovered a different strategy for attacking them. Senescent cells carry the type of DNA damage that should spur a protective protein, called p53, to put them down. Instead, the researchers found that a different protein, FOXO4, latches onto p53 and prevents it from doing its duty.

    To counteract this effect, De Keizer and colleagues designed a molecule, known as a peptide, that carries a shortened version of the segment of FOXO4 that attaches to p53. In a petri dish, this peptide prevented FOXO4 and p53 from hooking up, prompting senescent cells to commit suicide. But it spared healthy cells.

  11. So assuming that this peptide pans out to be everything we hope it to be.

    The $64,000 question – How long under it receives FDA approval?

    Or perhaps more importantly, how long until it is available to anyone willing to engage in medical tourism and at what price?

  12. Hope someone already started breeding those FOXO4 -/- mice.
    If they dont show health/lifespan improvements to controls then nothing to get excited about.

    • Not necessarily true, Gabor. FOXO4 has multiple functions. It may be that blocking the connection to p53 with a short-term intervention that knocks out senescent cells is beneficial, even if knocking out FOXO4 completely has serious side-effects.

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