$36,000
$24,120

The SENS Rejuvenation Biotechnology Companies

After the laboratory, the next stage of development in rejuvenation therapies involves the founding of biotechnology startups. There is no clear-cut point at which research stops being non-profit in the laboratory and starts being for-profit in a venture-funded startup. Every research team eyeballs the time and cost needed to get to the next level, something ready for the first human trial. Once that comes down to a gap that can be crossed with the combination of a seed round and angel investment round - say half a million to a million dollars and a year or two of work with a couple of clearly identifiable goals and go/no-go decisions - then the adventurous will make the leap. As I'm sure you've noticed it looks like a bear market is getting underway, but what better time to pull in investment for a project that might take a couple of years of heads-down work out of the limelight to reach the next stage? Bear markets only last a year or two, so by the time a new biotech startup has completed its first stage work successfully, it'll be ready to catch the headwinds of the next bull market.

Numerous lines of SENS rejuvenation research are, piece by piece, leaving the laboratory for the startup world. This is the success that we as a community have achieved with our years of charitable support for research aimed at advancing the state of the art. Whenever a new SENS-related biotechnology startup launches, bear in mind that a diverse group of people, investors and researchers, have looked at the technology and said "yes, we think can get a prototype therapy for human trials done in a couple of years." It is an important sign of progress, and one that is hard to fake: people with meaningful amounts of money on the line made those calls. You should expect our community to transition in part from one of fellow traveler non-profits and research groups to one made up equally of a network of startups, entrepreneurs, and investors of various stripes, from occasional angels to professionals at venture funds.

Here is a short list of interesting companies I am aware of that are working on SENS-related therapies at various stages, some very new, some years old, and proceeding at differing paces and with different strategies for development. They are not the only companies of interest to people who follow this space: I am omitting Arigos Biomedical, Organovo, and BioViva, among others, but the companies I list below are all very clearly working on aspects of SENS rejuvenation biotechnology. I'm certain there are others that I don't know about at this point - I am certainly far from well connected. I foresee a future in which in addition to the important work still ongoing in the laboratory, we can help to support a incubator-like environment of friendly companies under the SENS umbrella, helping one another succeed, each focused on one slice of the rejuvenation therapies needed to bring an end to aging. Those that succeed will act as guides for the growth of others: in diversity there is the greater chance of finding winning strategies. Importantly, among these companies today there are lot of people who are in this primarily to get the therapies built and out there and available. They are long-term SENS supporters. If they strike it rich, a good portion of that wealth is going to be reinvested in the next cycle of research development because, like us, they have a good idea of which of the two of life and money is more important. That is what success will look like once things become more commercial.

Gensight

I've posted on the topic of Gensight in the past. This is a French company with tens of millions in venture funding that is built on technology for allotopic expression of mitochondrial genes originally partly funded by the SENS Research Foundation. They are focused on generating a robust commercial implementation for one mitochondrial gene, initially to deploy gene therapies to treat hereditary mitochondrial disease. Creating such a robust implementation is an important foundation for a future effort in which all mitochondrial genes can be backed up to the cell nucleus, and thus the contribution of mitochondrial DNA damage to aging can be eliminated.

Human Rejuvenation Technologies

Human Rejuvenation Technologies is a venture run by philanthropist Jason Hope, who you may recall funded a sizable chunk of the ongoing work on glucosepane cross-link breaking at the SENS Research Foundation back a few years ago. Glucosepane cross-link breaker drug candidates seem to be a few years in the future yet, so Human Rejuvenation Technologies is instead working with a drug candidate for clearing a form of metabolic waste key to plaque formation in atherosclerosis. This candidate is one of the results produced by the long-running SENS Research Foundation LysoSENS program.

Ichor Therapeutics

Ichor Therapeutics has been around for a couple of years, and has done a good job in setting a sustainable lab business on the side. The interesting work here, however, is the continuation of SENS research programs aimed at removing the buildup of A2E, one of the components of lipofuscin that builds up in cells and interferes with cellular garbage disposal. Unusually among the forms of cellular damage, even those involving buildup of metabolic waste such as lipofusin, A2E is linked very directly and solidly to some forms of age-related disease that involve retinal degeneration. In most cases the fundamental damage that causes aging is separated from the end stage of disease by lengthy and barely understood chains of cause and consequence, but here it is very clear that getting rid of A2E is a good thing.

Oisin Biotechnologies

Oisin Biotechnologies is developing a senescent cell clearance therapy, an approach to treating aging that has definitely arrived with a splash: there are multiple methods demonstrated in mice, and a number of different groups at the point of launching commercial development efforts. The company was funded more than a year ago by the Methuselah Foundation and SENS Research Foundation, and you'll be hearing much more about them in the year ahead, I predict.

Pentraxin Therapeutics

Pentraxin Therapeutics is the oldest and slowest of these companies, founded way back in 2001. The SENS-relevant work started in 2008 or 2009 with a partnership with GlaxoSmithKline to develop a treatment to clear transthyretin amyloid, a form of metabolic waste that builds up with age and is linked to cardiovascular disease, osteoarthritis, and death by heart failure in the oldest human beings. A human trial recently produced very positive results, showing significant clearance of amyloid in patients, and this is consequently probably the furthest advanced of all SENS technologies. Unfortunately it is also the most locked up within the slow regulatory system and a Big Pharma partnership. It is hard to say what is going to happen next here, but don't hold your breath expecting to see anything in the clinic soon.

Unity Biotechnology

Unity Biotechnology has emerged from the first successful efforts to clear senescent cells via gene therapy, back in 2011, as well as ongoing programs such as those of the Campisi laboratory. They have a sizable staff for a startup, good venture backing, and are developing treatments based on these methods, but which will be more suitable for use in human patients. You no doubt saw the full court press in the media put on by the various organizational backers of Unity earlier this week. It is great to see such a large number of people pushing the SENS line of damage repair as the approach to treatment of aging. As more companies reach the point of gaining support from deep pockets in the venture community, we will see more of this media attention for SENS-like rejuvenation therapies.

Comments

Read the comments fightaging team! Spark are also jumping into the mitochondrial gene therapy space:

Spark Therapeutics have announced that they are also developing a gene therapy for LHON. With my laymans knowledge I think that LHON is only caused by mutations in the mitochondrial DNA. So perhaps Spark will be using the same (partially SENS funded) Mitochondrial Targeting Sequence method as Gensight are doing?

http://www.fiercebiotech.com/press-releases/spark-unveils-vision-having-10-clinical-stage-gene-therapy-programs-2018-in

http://www.gensight-biologics.com/index.php?page=mts

Posted by: Jim at February 6th, 2016 5:16 AM

"Among the programs unveiled for the first time were two new indications, including Leber hereditary optic neuropathy (LHON), an additional inherited retinal dystrophy (IRD) program, which affects over 7,500 patients, with an even greater number of patients at risk for losing their sight in the United States and the five major European markets (EU5). Within the Company's growing CNS portfolio, Spark unveiled its program targeting Huntington's disease (HD), a hereditary genetic disorder that affects over 60,000 patients in the United States and the EU5."

Posted by: Jim at February 6th, 2016 5:22 AM

@Jim: As I understand Spark, it's straight gene therapy rather than allotopic expression - deliver a working copy into mitochondria. The consensus so far seems to be that without removal of the damaged mitochondrial genomes, this may not be terribly effective for the scenario in aging due to the pace at which damaged genomes take over cells once they exist.

Posted by: Reason at February 6th, 2016 9:32 AM

@Jim @Reason

Hi Jim and Reason !

I hope that allotopic expression turns out great, but I have a feeling it is facing certain problems (for now it's for mitochondrial mutations, yet mitochondrial mutations are just one damage that apparently, in isolation, does nothing to intrinsic aging, is only correlative not causative) and it's an area I'm not very informed.

For example, if CR is capable of inducing Complex I and OXPHOS complexes in mitochondria that are necessary to produce ATP; why is it that CR can't make an animal become immortal then ? Obviously the reason is damage accrual is massive.
Because allotopic expression is trying that
by stopping mitochondrial DNA fragmentation. Yet, CR does exactly what allotopic expression is trying to do, that is increasing activity/allowing assembly of Complex I OXPHOS (oxidative phosphorilation process) in mitochondria ETC (electron transport chain) to occur and make the mitochondrial respiration restoration bioenergetics happen to produce the ATP that is needed to energize the cell. Also, allotopic expression may try to use AOX (alternative oxidase) to obviate use of Cytochrome oxidase (Complex IV) and Complex I. Yet, other studies that overexpressed AOX bypass did not make any difference on mice or drosophila fruit fly lifespan (in fact it restored senescence in some). Same thing for mitochondrial hormesis which increases Complex OXPHOS activity - yet can't stop the organism from dying of damage accrual - this is a double-edged sword when activated COX (cytochrome C oxidase which produces oxidative damage by copper-iron ROS hydroxyl radical). We understand that mitochondrial ROS are behind all of this; but there is a blurred line; and allotopic expression of 13 mitochondrial proteins from nuclear back to mitochondria, in theory, qould not seem to stop the aging process. I feel it is a therapeutic effect or let's say a 'fidelity' of genome; and keeps the genome functional. Such as mitochondrial mutations show.

They are part of the aging but are not really a - cause - to aging (in isolation at least). They compromise genome stability and as such - will cut an organisms lifespan short - of what it can accomplish in terms of MLSP; simply by creating a state of frailty/inflammation (inducible senescence) by these mitochondrial mutations. But it won't have much effect on intrinsic aging replicative senescence - which that one is cause by oxidative stress damage accrual that is visible in mtDNA as oxidative lesions (8-Oxo-2'-deoxyguanosine (8-oxo-dG) 8-hydroxy-2' -deoxyguanosine (8-OHdG) or 8-oxo-7,8-dihydro-2' -deoxyguanosine (8-oxodG)). When OXPHOS is assembled again, ATP rises but so does the continuity of 'aging' continues its course (damage accrual). That is why I am slightly skeptic allotopic expression could simply turn the mitochondria to 'anew' and everything is arranged. It is targeting the right place, for mitochondrias are the crucial area causal to MLSP, since their innermembranes are the main iniators (by complexes ROS production) and propagators (innermembrane phospholipid degradation/peroxidation) of all damages. I feel the aging process will be slowed down by allotopic process, I'm not sure if it will Stop the aging process - enough - to compensate - enough, or it will be another catch-up game we lose at very quick.

Of course, this is just for that therapy alone in isolation (which defeasts the purpose), which would not be enough and combining all the therapies - may still not be enough. As some here say that combining all 7 therapies would give perhaps a chance to live to a 150 or so. But this talk of 1000 years with the combined therapies is slightly over the top, to some. Simply because the damages are way too numerous and diversified, that even all combined therapies cannot stop them all; they may bring back the body by a 30 years behind but the notion that you can repeat this continuously without some loss somewhere is wrong. We could probably repeatly go back by 30 years for a limited number of times. Say two or three times, and then's damages catch-up would win. Things like saying ''We can repeat it infinitely because we are back to 'exact' biological age 30 years earlier, so it's like pressing 'Rewind' button ad evitam eternam''. I have difficulty with that because it's like saying the damages are evaporated and things continue as if nothing happened ? When we know that the endless damages end up winning one way or another. If we can't stop mitochondrias from propagating this damage, it's almost impossible to increase MLSP.

Anyway, I hope it turns out good ! As some said, if SENS or any related company can make a immortal yeast; it will be a good start to making a believer. : P

1. Evidence that mutation accumulation does not cause aging in
Saccharomyces cerevisiae
http://onlinelibrary.wiley.com/doi/10.1111/acel.12290/pdf

Posted by: CANanonymity at February 6th, 2016 11:35 AM

150 isn't a bad number, but talks of over 1000 seem pointless to me. If it were to happen, we're probably 940-950 years away from seeing that. Even if someone lives to be 150, we probably won't see it happen for another 90-100 years anyway (if I had to venture a guess), which will allow medicine to advance that much more. It's all speculation of course, but talks of extreme longevity don't really do any good, as there are still many years to go before we see these numbers being reached.

Posted by: Ham at February 6th, 2016 12:24 PM

I don't see any logical connection between the lenght of time to the first 1000-years old and it being pointless to talk about it. If aging is eliminated, current mortality rates for people in their 20s produce a life expectancy of that order of magnitude.

Also, I don't consider it harmful. At least for me, it's very inspiring to know what can be attained with these investigations. For me, death has always been the worst enemy, much worse than disease or decrepitude.

Posted by: Antonio at February 6th, 2016 1:46 PM

I just personally think it's pointless talking about 1000 year life spans because most people currently still don't even want to think about living to 120 or 150, even if it's in good health. You know all the reasons that people give as to why. Talking about living to 1000 just makes it seem even more overwhelming and I would imagine probably makes people view the topic as pseudoscience. All of this is on top of the fact that most people generally don't even make it to 90 yet. I have no issues personally with the prospects of 150, or 1000, or somewhere in between, but I'm sure you've seen the surveys where most people disagree with us and can't imagine living that long.

Think about how long ago 950 years was, and how many incredible (and incredibly bad) things have happened. Imagining you were there to see them all is a pretty mindblowing thought when you actually sit and think about it. It was a really long time ago. It's probably hard for most people to think about the prospect of living from now, until that far in the future as well. I obviously can't speak for everyone's feelings on the matter, but it's just how I suspect many people would feel when talking about 1000 year lifespans. Which is why I don't think really talking about that length of time is really helpful, but of course that's just my 2ยข. I personally would obviously love the opportunity though.

The point I was making before was, if it IS possible, we won't know for that many years, it's a long ways out to speculate. Anyway,I don't disagree with your feelings towards death, and what can be achieved though. I largely feel the same way. We seem to be in the (hopefully growing) minority though.

Posted by: Ham at February 6th, 2016 2:11 PM

Yes, I know the widespread opinions, but I think it's better to not hiding anything from the public and always tell them the truth, even if they don't believe it. On the long term, it's more harmful not to do so, I think. When the reason for considering it psedoscience is their beliefs and ignorance, you can correct them with detailed explanations and patience, at least in some cases. OTOH, when the reason is that you concealed information from them, then it's more difficult to change their opinions, because they consider you a liar.

About the feelings of the general public about 1000 years lifespans, I know the surveys results. Anyway, between the people that I know personally, none of them want to die, even the oldest ones. So I think that probably the surveys results are mainly due to some misconceptions, like the Tithonous error, not considering life extension as feasible, etc. I think that probably most of that people, when the time comes to choose between using or not using LE therapies, will use them, contrary to what they said before.

Posted by: Antonio at February 6th, 2016 2:58 PM

Hi,

I agree with you. Still, even if it does (and right now is) exaggerated to talk about huge lifespans, the more we keep it 'as exaggerated', the more it will stay like that. I know exaggerated talking hinders development and as you said before, it can make investors and money disappear because people think it's all fake bs and snake oil. So yes we have to have strong proof to back our wild claims (1000-year lifespan), but talking about it will allow it to becoming the norm, not some fantasy joke. Because 99% people will say it's impossible and a joke. And like you mentioned, some can't even fathom living to 120, it's either Too Long or they fear their health will not be good enough by then thus prefer to die than suffer as centenarian elders.
That is the mindset of the near entire human population, we are but of the few who understand biology and biogerontogy to know that death is not an unstoppable fate, or at least, it can be pushed back much farther.

The more people talk that they Might, they Could, (in the future) they Can live much longer than 120; people will start to see the benefits and think for a second...Could - It - Be - Possible ? ....

Sort of like a realization, right now it's simply the consensus that you are going to die before 120. And that's it. It's no good, it's okay to talk about it while still being reasonable. Even talking about 1000 or few centuries lifespan is reasonable, even if sounds, extreme. We are not talking about immortality here. Just a much much Much Muccch longer human lifespan than the measly 120 years we got. People will think, How Could 120 Years Be Small ? It Is Hugggeee!! 120 years....lol...they think it's the biggest thing ever and in their mind, any thing that goes above that -must- die...sad...

Although I still have fate, there was a survey that asked if people wanted to live above 120, most said no because of fear of old decrepit frail ailing/hurting state at those extremes, but when the question was changed if they wanted to live above 120 if health was good, the results were quite different and now almost 3/4 of people said Yes, thus -wanted- major lifespan extension above 120 if it were available and protected them against decrepit/diseased state of old age.

That means what ? It means people are willing, only if health quality is maintained, those that don't want to because 'life is too long and boring above 120' well they will be a shrinking bunch for they will accept death over living, that leaves more and more people joining the pro-extreme biorejuvenation Real lifespan extension; not the ''I give you 30 years extra or do calorie restriction which ever one you want...and then you die''.

So to change society and make things currently 'mythical' 'tacky' 'a big joke' you have to talk about them, including the extreme stuff. We must concentrate of realistic talking of going up to 120 or becoming centenarian; we can also, still, talk 'less realistically' of the implausible/improbable possibilty of going up to 150, 300, 1000 or more. And still, be grounded in reality that it may (or most likely) will never happen in our lifetime. But in our lifetime, we'll talk about it, too.

Posted by: CANanonymity at February 6th, 2016 3:29 PM

@CANanonymity

I wouldn't personally expect 1000, or even 300. I don't think anyone should realistically expect that yet, but that's just my opinion. But I wouldn't think 120-150 is out of the range of possibilities, considering there have been many people that have been super-centenarians, without any types of interventions. If you're in your 20's-40's now that's between ~80ish and ~100ish years before 120. So, depending on current age, I don't know if I necessarily agree with what you said about how it most likely will never happen in our lifetime (for 120-150, that is). It's a lot of time for improvements in treatments.

Honestly, if you make it to 120, or 150, there probably isn't a reason you won't be able to go further, but who knows. Hopefully these companies that are jumping in on senescent cells and other things now get something working, and into trials, and see how it goes.

Posted by: Ham at February 6th, 2016 4:24 PM

@Ham

Hi Ham, I might be too optimistic :D or foolishly blind/drinking the magical Kool-Aid. I just sense the power of this revolutionary work. It is like a dream come true and waking up from that dream forever; and never going to sleep forever (death). What is there not to like ?

''if you make it to 120, or 150, there probably isn't a reason you won't be able to go further, but who knows''

Exactly, your chances should in theory rise as you make it farther and farther - without any therapies (just like those supercentenarians today). The problem or let's say the sad fact is that if in the next 100 years we still haven't been capable of greatly extending lifespan. It's game over for us (living today), if in, let's say (ideally) in 50 years time, they do find, we (us today) will be in our 80s-90s-100s (or dead already). Unless we are lucky genetically and Even then,
as it was noted from Aubrey de Grey's paper (longevity escape velocity), a person who is above 80 (that is US in the near future), will never be able to twarth the - damages that have Already accumulate (total damage accrual) up to 80 years old. Thus, the effect of these biorejuvenation therapies will be smaller and smaller, as the person taking them is older and older (simply by their total accrued damage in their life at that point). Unless these therapies can magically make the damage disappear there is no way (us) today will live above 150 years old; we may make it 120.

And that is why, I feel, we must start talking about 300, 1000 year lifespan Right Now, not in 100 or 500 years; but right this moment because - us - will be getting the short end of the stick simply because we are 'born just too early' in the timeline by one generation too quick (
''Tough LucK...Suuuckkker'') : D heheh...D*mn it...lol now I wished I was born 'in the future' because think about it, just 20 years ago we Never - Ever thought it Could be possible, now that view is changing; let's talk about it, right this moment because I 'feel' my clock is ticking; so yeah 120? 300? 1000? It's all good Bring it on the fastest the better cause I don't want be dead when it happens. Let's make those scientists commit to the impossible ; D and not aim 'for ''ok''. The more they work on aiming 'for the moon' the more chances we got of 'falling in (much higher) in the stars' than if they said ''we are aiming 'just high' enough' so don't expect anything impressive and we are going to fail also...in fact, you know what, your dead anyways.''

Posted by: CANanonymity at February 6th, 2016 11:35 PM

@Ham
Here are the therapies and a wild optimistic guess (uneducated 3 cents, may seem overly optimistic, but it is still good in realistic way). Some of these combination, may work in synergy or cancel each other out/rendering the effect half or a third or a fourth of its total addition (because they use redundant pathways like IGF or mTOR/NF-Kb). At worst, it gives a total of 125% increase in maximal lifespan (by addition, making humans reach 270 years MLSP) and at the best it gives 210% increase in maximal lifespan (making humans reach 372 years MLSP).
All of these therapies combined, if none were to increase MLSP, make any human reach 122 MLSP by their total 240% average/health span increase.
Of course, this is all in addition, but as said, some may cancel each other's effect (as such, in reality could only be (half) 60-120% to a (quarter) 30-60% of MLSP extension) or work in synergy (if they do work in exponent/multiplication-synergy-between-each-other it would indeed make us live to a 1000 years old). Most studies point to no real synergy and cancelation (as shown in CR studies that clearly show - all of the redundant pathways make same result combined or when done alone, because they are mutually-Inter-Dependent). (meaning these effects - do not - translate 1 + 1 + 1, but rather fractional combined effects 0.25 + 0.25 + 0.25...)

Stem cells and tissue engineering: RepleniSENS

(15-30% extension maximal lifespan)
Stem cell replenishment hits the catch-up game problem, stem cells lose telomeres. Although, you can repeat the process and have infinite stem cells from the lab, these injections do not stop the process of aging (as was shown in mesenchymal and adipose stem cell injecion in mice giving mild mimetic CR - therapeutic effect on 'health'.

Removal of telomere-lengthening machinery: OncoSENS

(0% maximal extension, but increase in average lifespan/healthspan by removing cancer formation).
Good to stop cancer. Bad to remove telomerase for telomerase-needing cells (sexual, immune leukocyte and certain cells that depend on telomerase for the very survival. But also, bad because telomerase acts as a mild ROS reducer (outside of its telomere lengthening role) and genetic stability inducer in the nucleus - and -mitochondria, I would guess even cytosol (since it is shuttled back and forth between the two depending on oxidative stress).
Reduction of telomerase is better (in whole body). Removal in targeted cancer cells is perfect. Removal (in whole body) is probably way too drastic (as mice that lose telomerase, die quicker, ok they have telomerase by nature and we don't because of our somatic cells devoid of telomerase - still certain of our cells use 'some' telomerase and if it is deprived it could compromise the immune system. I think removal telomerase is great, but only in cancer cells.

Allotopic expression of 13 proteins: MitoSENS

(0% increase in maximum lifespan, 15-30% average/healthspan by removal of mutation disease 'mitopathy').
Mitochondrial mutations, allotopic expression to relieve mitochondrial mutations, when a paper showed that mitochondrial mutations are not causal at all to intrinsic aging (in isolation), and only correlative. But increase genomic instability/fragility/disease/pathology - but no effect on regular intrinsic aging process to reach 'regular' human specie healthy maximal lifespan. Plus, as was shown with CR and mitohormesis, OXPHOS complex I-IV recontruction, after failure, by mitochondrial protein import is what happens in these therapies that alter the complexes to be much more efficient and reduce mitoROS production and mtDNA degeneration. Still doesn't stop them from killing you down the line and neither stop aging process of damage accrual from happening.

Targeted ablation: ApoptoSENS

(15-30% average lifespan/health extension by removal of pathology/disease a bit like mutations removal, perhaps up to 50% and 15-20% maximal lifespan extension (doubtful though, even if they remove +90% of senescent cells) Senolytics, though nowhere as strong as a therapy, still show the intrinsic limit of this being that senescent cells are not the Major contributor to intrinsic aging. They are Major contributors to Inflammaging and pathology (inducible senescence (spontaneous, Ras/p53/p16) - not replicative senescence-based (intrinsic, p53/p21)) as such don't 'drive' the intrinsic process, but definitely drive the pathological process.

AGE-breaking molecules; tissue engineering: GlycoSENS
(30% increase in average and maximal lifespan at the most, because CR reduces already AGEs and slows down crosslinks. Although it does not remove already formed crosslinks, so if we remove crosslinks, it could go up to 70-80% increase, but a 100% increase I don't think so. Other damages chime in).

Immunotherapeutic clearance: AmyloSENS
(30-50% increase in average/health lifespan, 15-30% for maximum lifespan.
Amyloid and transthyretin removal will not stop aging (centenarians accumulate transthyretin, but clearly if it is removed it does not stop aging but slows it, as there are other aggregates and lipofuscin for example; it just 'one' damage among others. People that don't get alzheimer's, instead of dying at 73 like my uncle who died of Alzheimer's...well they could reach 122 like Jeanne Calment, with an intact brain...it does not stop brain involution from ongoing aging process. Meaning Alzheimer's is a disease (that accelerates brain death) that halts the MLSP potential but is not 'the' intrinsic aging process. Same goes for transthyretin.

Novel lysosomal hydrolases: LysoSENS
50-possibly 100% average and maximal lifespan extension, above that is pure speculation, because there are still other factors on the line (like that ECM MMP problem not degrading glucosepane and whatnot). Not much higher than 100% because I don't think we can Entirely stop lipofuscin accrual; we will remove it as best as we can with nanorobots other than that, it will accumulate and continue its course of messing things up in the autophagic system and producing ever increasing ROS. Still, Intracelluar and cytosolic removal of aggregates such lipofuscin, drusen, A2E and ceroid is great start, and the most significative one.

Posted by: CANanonymity at February 7th, 2016 1:12 AM

PS: one more thing, these results are when they are started - from Very birth up to no later than 40 years old.
If these therapies are started at half MLSP (60 years old) or at near-MLSP (90-110 years old), they halve or even make a quarter of the effect, as such at best 60-120% MLSP/at worst 30-60% MLSP starting at 60 years old (from damage accrued so far), and at best 30-60% MLSP/at worst 15-30% MLSP starting at 110 years old.

Posted by: CANanonymity at February 7th, 2016 1:54 AM

Where are you getting the percentages for increases in lifespan, and the years/effectiveness of the therapies when administered? I'm mostly interested in the years administered comments, because I know during an AMA (this years, or maybe last, I'm sure I can find it if you're interested) someone asked if it would make sense to give someone SENS treatments at 20-25, and Aubrey de Grey said it would likely have no effect, and it would make the most sense if the person were already in their 50's. He also said it shouldn't necessarily matter how old you are when receiving the treatments. Whether or not any of this will be true remains to be seen, I suppose.

Posted by: Ham at February 7th, 2016 6:55 AM

@Ham

Mostly from CR (calorie restriction) comparison, I'm not saying CR is the Perfect Model that answers everything and is 1:1 translation, no - but an 'estimate', CR thought us a - lot. There are what some 500,000 papers on calorie restriction ? Surely in some of them they talked about all of these therapies, wether is touches senescent cells, AGEs or what not, every CR study tried to see the effect of CR on these damages and what exact pathways allowed CR to increase mice Maximal lifespan by 30-50%. They realized that much of these pathways - act in concert - together to make that 'combined effect' if you cut - one single - of these pathways...boom the 'connection-combination' between these multiple pathways now fail. So they are - all - required to create the effect of CR. CR is not an isolated effect, its multiple (millions?) pathways that act all - at the same time - and give that final CR effect of
30-50% MLSP increase.

If we extrapolate these notions and compare that these therapies we can put smaller percentages, from the percentages that were gained by individual therapies that tried to do what these therapies will do (and that were - never - more than 50% increase of lifespan, wether maximal or average/health), thus we can infer that, also, to these rejuvenation therapies.

And that is because, they too face the big problem (like the other studies faced head on) : damage accrual is an ongoing thing and will keep on going, wether you slow it down or remove some of it (which is what these therapies will try to do; so immediately we can assign fraction percentages, rather than say : ''yes it will multiply and synergize so many times that percentages increase will be 5000% ,500000%, huggeeee!''....no (just my opinion). Unless there IS synergy, the percentages will remain (like the other studies) below 100% for each therapy - and that's because damages will hinder the potential of the therapy; meaning a therapy has the Power for thousands % increase - but damage accrual 'problem' reduces it dramatically to below 100%..

''someone asked if it would make sense to give someone SENS treatments at 20-25, and Aubrey de Grey said it would likely have no effect, and it would make the most sense if the person were already in their 50's. He also said it shouldn't necessarily matter how old you are when receiving the treatments. Whether or not any of this will be true remains to be seen, I suppose''

I am guessing he had a memory blank at that moment (he forgot his own paper research results...Longevity Escape Velocity is quite real but also exaggerated 'on paper', his paper showed you Can Not Avoid Damage Accrual Curves that bring you to your death (damage accrual means you are a downhill slope to your end, one day or another; and much quicker than his predictions)
And then saying stuff like if we repeat therapies continuously there is no mortality (rate increase) ever (escape death/longevity velocity escaping death) so we can keep a 60 year old forever young, when we know that small % damages Will accumulate one way or another even we took these 7 therapies day and night for entire life; for the simple fact damage accrual is too massive and hard to disentangle in a human body; even if 7 therapies made us lose 99.999% damages, there is still 0.001% damage going on and killing us extremely slowly).

He forgot that age Does matter (for damage accrual is the Single Biggest determinant of how strong these therapie will work...how can infer that ? Because CR started from very late age/at birth does not have the same effect - as CR started from early age. CR makes the young live up to 50%, while old mice CR is almost nill on MLSP. The damage incurred in these old mice is Irreversible and Stops the effect of the therapies. So we must Removes the Already Accumulated damages in Elderly people - to get same effect when starting therapy in early age young people with no damage accrual from young life. Same goes for Carnosine which increases Young mice lifespan when started from Young point. Old mice who receive Carnosine have - no - or very little extension of maximum lifespan. And that is repeated with other antioxidants or therapies that slow some of the damages that the 7 therapies will try to reduce. So yes, I believe (just my opinion) aging - after 40 years old - will have impact, incidence, importance, percentage and susceptibility outcome effect from that point on.

I think we said that starting the therapy at 50 years will be better than 25 or make no difference; is that he meant - there Were damages at 50 - to be repaired where as at 25 there is nothing to repair.
But what he forgot...his own analogy...of the rusting car...a car must be kept pristine state forever, if you want to keep it forever; it if continues to rust a little more and you repair it; you gave it some extra time, ...but then it continues to rust some more...catch-up game...one day you - can't - repair it anymore because the total damage accrued - beyond further repair - been reached. Meaning these Irreversible damages still won fractional 0.000000001% percentage increase each time you repaired things but some micro-damage stayed...you slowed down the car's deterioration dramatically by keeping on repairing it - you did not stop or reverse it though. One day, the car broke down. He simply forgot the car analogy and that rust is rust/oxidation is oxidation/damage is damage, especially if you accumulated a lot of it by a long life already, no way around it.

Posted by: CANanonymity at February 7th, 2016 11:04 AM

@Ham

Thanks for the link.

''No effect. Would you take a brand new car in for an annual checkup? Best to wait until middle age, since the therapies will be getting better and more effectiev all the time.''

He knows his stuff, but here, in my language we say : ''y se trahit un ti peu'' (''he is being lil bit non-true (only non-pejorative figurative speech) to his own self'', and as such somewhat contradicts (denial or change of mind?) his previous research paper claims), it's almost as if someone told him to say that (his agent?) or it was scripted to him. Or he forgot to bring his notes or 'just forgot...' that damages that you have so far accrued are not thin air.

I think he may have hooked on too strongly on the Hip Therapy Kool-Aid bandwagon ; )
'Hope to be saved by Repair-All-Damage Therapy-Everything-A-OK' and
'wait till your 50..60...70....80..90..
and then, if not dead or near-dead...
(by your total damage your suffered), get that therapy to be saved - but never in any circumstance do it before feeling half-dead, which happens around 70 or so....',

(joke)

: P
More seriously,
He, himself of all people on earth since he attack aging like no other,
must be the first one to know the
- most - of the precious/precary/finitness/volatility - essence - and - shortness - and (ultra-fast) - speed - of passing time and (short) human lifespan. We don't have an eternity to wait. Many will die waiting, 10, 20, 30 years...too long, Way too long.

I know they would say...''well, it could take 300 years!..what do you expect! do you prefer 30 or 300 years wait ???!??' heh..of course 30 years it is very small in the 'grand scheme' of 'future humanity'...problem is..We (-Us- Today living people who are willing to shell enough dough to live longer) may not 'be' 'future humanity' who enjoy the fruit of his labor. Sad. We'll be dead Long before that, waiting for our therapy to make it to the light of day in our hastening and shortening life.

I know we can't expect (anything) much more than what they can do to advance their own research/inventions. So let's just support them, just be real that it may not turn out much above 150-175 years in very high optimism (so it may even be worse and not make anyone reach more than 122 because of said accrued damage problem).
Also, his bit that 'someone else/other company' could find the elixir of youth forever is possible as therapies 'pop' up; still it takes a little longer than that; and SENS is the - only - thing remotely in the target to reach that. There is nothing else; so yes, not out of the woods and we got SENS to guide us in it; anything else ? It will have to show up very soon.

It's like the HourGlass Sand-Clock, each grain is pouring down each second the tiny hole and our upper-compartment sand is evaporating down the sink hole, right now. And The Grim Reaper is Right Next to it, counting each grain go down, making sure to not miss one grain in full satisfaction of the horror of our never-fast-enough impending doom and wishing the hourglass to just explode to finish us right now. Yeah, I really have 30 years to wait. Says nobody. :D

Posted by: CANanonymity at February 7th, 2016 1:28 PM

CANAnonymity, just stop. Seriously. Just stop, in general.

CR, a very modest form of damage slowing has nothing whatsoever to do with damage reversal. The reason Aubrey said that it's pointless to give a 20-25 year old SENS therapies is because that person hasn't accumulated enough damage for those therapies to be worth it.

Talking about years and percentages is making stuff up. There is no mystic "damage accrual" that can't be identified. If it can't be identified, it doesn't exist.

And if there is something missed that will kill people in five hundred years, we have five hundred years to figure out what it is and how to get rid of it.

Posted by: Slicer at February 8th, 2016 9:27 AM

We know the forms of waste and signalling decline that occur and they occur. How will such therapies influence lifespan? We do not know, we will not know until we test them and we cannot know.

"Guesswork is poor, logic is better and data is king"

The project I am working on is in communication with various labs working with SENS therapies, it is not really a stretch for us to combine these things once available and see what happens.

Aubrey has repeatedly said in the past that the SENS system is designed to work as a suite of therapies not in isolation. Will single therapies help? probably but until we get them on the bench we do not know and cannot know.

So lets support the work to get them on the bench and not try to guess!

Posted by: Steve H at February 8th, 2016 10:08 AM

@Slicer

Hi Slicer ! I apologize : D for going amok... I respect your opinion, I'm a tiny bit on the fence on this one.

''CR, a very modest form of damage slowing has nothing whatsoever to do with damage reversal.''

Yes, exactly it is a modest form of slowing damage and indeed, it does not have anything to do with damage reversal, but it does have something to do with slowing them and being capable of extending MLSP - which is what is important here. MLSP extension by CR is the most important factor that makes -very- applicable.

But can you tell me what damage reversal is and how exactly is any of these therapies making that...I believe none of them, Slicer, stop the main problem, which is that damage continue to add up - despite whether you slow them - or Reverse them - you only do that to a % of it, there is still 'some' damage that wins...

These therapies, are saying, ''We Got You Covered'' ''All Damages Locked- and - Removed - All of Them''.....no I'm sorry. And especially, my point, that Right Now, You, have damage in You. And IT counts about how much these therapies will work.

I think you understand my point. The point is obviously to try to offset the loss (damages) with gains (repair/reversal), just like when you go play at the casino (analogy), you need to gain more cash then lose cash otherwise you end up broke and 'under' (minus in your account as your borrow money to try offset further loss and 'hope' to make gains). And what is important to distinguish is that these - micro - damage are irreversible. While you might reverse 99.99% of them, life is, nothing is perfect, you could not stop it all, not that 0.0000000001% damage, at least. Of course, such small damage accrual, what make these therapies capable of having someone reach 1000 years easy (I mean 0.0000000....0.1% how big of an impact can that have on a lifespan, almost none and you are near-immortal...right ?.....well...this is only 'an example' and I'm quite sure the small damages 'that get away with it in you' will be -much- higher than those fractions I'm giving you as example to understand...thus, they - will - have an impact on your life despite you taking 7 or 14 of these therapies combined day and night.

''The reason Aubrey said that it's pointless to give a 20-25 year old SENS therapies is because that person hasn't accumulated enough damage for those therapies to be worth it.''

I know,, that's why I said : ''I think he meant that at 25 there is no damage to repair..while at 50 there IS damage to repair..'' so you wait till then right ? What would be the point to do it now at your 20 years old...if you haven't go enough damage....but what he forgets...is there IS some damage -even- in a 20 year old...that is why, studies that tried to make a therapy start later in an organisms lifespan nearly - always- had smaller results. It's funny when they started the therapy at birth the organism lived the longest and benefitted the most...as soon as these therapies (such as CR) where started at 15%, 20%, 25%, 30%, 40,% 50%,....heck at 75%...the results were always poorer. And it was Very Obvious the reason, why...when you start late - you arrive late...damages had accumulated Even in the youngest ones...and it nullified Some of the benefits of the therapy when started later in the organisms lifespan.

I will trust him that yeah...most likely below 40 years old, your damage is quite low that is won't make That Much difference..yes...but above 40 and saying 'wait to middle ages or higher'...no...that's too late sadly. Damages come dramatically faster after 40 or so years old (in humans).

''Talking about years and percentages is making stuff up. There is no mystic "damage accrual" that can't be identified. If it can't be identified, it doesn't exist.''

It was just 'random estimates' if these therapies 'add up' in a certain reaslistic way (we can infer that, because for example, metformin is taking by humans, and you won't see them go above 122 years old, yet metformin reduces these damages the therapies will remove, so we got a starting point even if one may reverse and the other slows damage slightly...it doesn't matter, the results give us an 'rough' estimate point to have a sort of idea. Because if they multiply and synergize (which is almost 99% sure it won't (or not strongly that is, because of 'redundancy interdepedent pathways' problem)), then yes, all said is BS, otherwise what I said could be quite a rough-going but not bad estimate).

I know when can almost identify all damages, it doesn't stop them from happening and continuing to 'age' you....I hope we can identify it all - and reverse it all TOO. but my bets on that are small. I think we will slow it quite a bit but Not reverse it like you think these therapies will do. I explained above why it wouldn't Reverse damages...that is because these damages are irreversible chemistry and once you them, it's too bad- so sad. Most of these therapies cannot stop them; LysoSENS yes it could remove lipofuscin. but it does not stop the ongoing 'Oxidative Stress' at mitochondrias from happening, which MitoSENS wants to try to mitigate by allotopic import (it still does not stop Complex OXPHOS oxidative stress problem even if you 'rebuild' it in the mitochondrias, mitochondrias are the Key Element that Kill us, because they produce ROS (by Cytochrome C Oxidase and Complex I-III in ETC) that destroys mtDNA by membrane degradation (peroxidation propagation) and unless we can replace that mtDNA, the aging process will continue, 7 of these therapies, including CR or not).

''And if there is something missed that will kill people in five hundred years, we have five hundred years to figure out what it is and how to get rid of it.''

: ) yes we have time...only 'we' (us living people) don't...we will be dead, Slicer. 500 years seriously?...we won't tough 30 or so - to allow us 500 years extra. Time is of critical essence, we have very little left, we need those therapies in 50 years or less. otherwise, game over (for us today).

I apologize, it's just my slight skepticism taking over my optimism, I am being very optimistic about it but I don't shy from talking of the very potential pitfalls some shy away from.

@Steve

"Guesswork is poor, logic is better and data is king...
Aubrey has repeatedly said in the past that the SENS system is designed to work as a suite of therapies not in isolation. Will single therapies help? probably but until we get them on the bench we do not know and cannot know.
So lets support the work to get them on the bench and not try to guess!"

Hi Steve ! It's true...it is just me 'venting' vapor...I wast just trying to extrapolate this and I know what I'm saying is just 'that'...I was just trying to extrapolate the data available in CR (even if it only slows damages, it has meaning) to apply in these therapies as rough estimate...it maybe totally whack I give it to you, but it gives some kind of 'rough' idea...that could be 100% false. I will accept it. But it could be 'not that farr-off'...it just me 'speculating' ...'it's all. : )...

Like the example I gave of metformin, people take metformin (humans), my father took metformin for 15 years Steve...so yeah I know what I'm talking about on that part..did he rejuvenate by 50 years and his gray hair magically disappear ? No....it slows damages and won't make them live above 122 years MLSP, in humans, so - gives us a good estimate of the 'power' of damage slowing (same as CR in humans...which in mice is dramatic...but humans could be mild,again reducing the 'power' of damage slowing, and why damage removal/Reversal(yes)/slowing may be much smaller than what we hoped because damage accrual is an ongoing problem, like a mega freight train you can't stop but just slow down or explode a couple of its wagons to make it smaller) that we can infer/extrapolate, and we will see the effect of damage removal (if it even does happen, like glucosepane crosslink removal...just 'one' damage among other thousands...).

You are right, let's support them and be less guessing, so I apologize. I don't want to demean or reduce the greatness of their inventions. I might be overanalytic and extrapolating/speculating sometimes. : D Still, that is the job of the scientists, journalists, but laypeople too can do it, if they understand things a bit.

Posted by: CANanonymity at February 8th, 2016 11:37 AM

@CANanonymity:

Your logic is bad. You are effectively saying that because the damage is so great, repairing the damage won't work.

But *logically* if the damage is repaired then it is no longer so bad.

You're basically just saying it can't be done.

I on the other hand will wait and see. There is a long line of distinguished scientists who said e.g. human powered flight was impossible.

They were wrong.

Posted by: xd at July 3rd, 2016 12:42 AM

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