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
Discussion
36 reader comments
Imported threads are marked Archive. New comments are welcome and moderated for spam.
Hi Josh. What do you think of the Dr. Sinclair study on NAD out last week?
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.
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?
I wish this peptide had a name. I couldn't find a name for it when reading the earlier reports.
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.
http://www.sciencemag.org/news/2017/03/molecule-kills-elderly-cells-reduces-signs-aging-mice
http://www.prnewswire.com/news-releases/unity-biotechnology-announces-116-million-series-b-financing-300352831.html
US$116million for discovering synthetic molecule specifically eliminating senescent cells. Investors include Jeff Bezos
Thank you - I didn't realize this prize was out there.
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.
I wonder why Peter de Keizer says that when you are 65, you might get an injection. Why not much sooner?
https://www.theguardian.com/science/2017/mar/23/purging-the-body-of-retired-cells-could-reverse-ageing-study-shows
This is based on research done over four years ago. We know what the so-called FOXO4 peptide is.
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 lifespan.io?
- 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 lifespan.io 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.
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 ( https://www.google.com/patents/WO2011119722A2?cl=en ) 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.
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.
Fluoroquinolones can be pretty bad news for tendons and nerves, particularly long term.
This is largely due to ROS damage, which can be mitigated using MitoQ as prophylaxis:
https://www.ncbi.nlm.nih.gov/pubmed/19235604
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.