$36,000
$25,176

The Geroscience Network: Determined to Slow Aging through Medical Science

Across the last twenty years or so two very important, slow-moving battles over ideas and strategy have been fought within and around the aging research community. The first was to gain acknowledgement that the treatment of aging as a medical condition is a viable goal, and thus obtain the necessary support to make progress towards that goal. Even as recently as fifteen years ago ago, after years of extending the lifespan of laboratory animals in various ways, treating aging was still more or less a forbidden topic in the research community. Thankfully we have a long way since then in the matter of ideas, and it was a tough and long-running uphill process of advocacy and persuasion - a great deal of work was required to create change. Today we can say that this first battle is near done and finished, with only the mopping up remaining to be accomplished within the scientific community. Those who a decade ago dismissed the goal of treating aging or simply remained silent are now ready to talk in public and provide support. The public at large is unfortunately still behind the times, much less informed or convinced on the matter of aging, but that will change too.

It is the second battle within the scientific community that is now more of a concern for advocates - certainly more of a concern for this advocate. That battle is to shape the research strategies that are funded and pursued: in short whether to try to modestly slow aging or to aim to build rejuvenation therapies capable of reversing aging. When it comes to the future of our health and longevity, this is just as important as the efforts needed to move the research community to support the treatment of aging at all, and at this point has much further to go to a satisfactory conclusion. Sadly we live in a world in which, for various historical and regulatory reasons, the research community is almost entirely set on trying to modestly slow aging. Research groups follow the traditional approach of drug development, searching for compounds that can alter the operation of metabolism so as to slow down some of the changes that accompany aging. This is enormously expensive and has a low rate of success - you can look at the failed efforts to produce calorie restriction mimetics, for example, such as the hundreds of millions of dollars and a decade put into sirtuin research with nothing to show for it at the end. Current efforts to repurpose the drug metformin are likely to end up in the same place: enormous sums and a great deal of effort are spent chasing effects that are tiny.

Aging is all about damage accumulation. Slowing aging means a slower pace at which damage accrues. Reversing aging means repairing that damage - and thus there are ways to do much better than merely tinkering metabolism to somewhat slow down the arrival of new damage. Since the research community has a very good catalog of the damage that causes aging, researchers are in a position to build treatments to repair it, therapies that can in principle produce rejuvenation. Those treatments have been planned and visualized in great detail for years now, and in a sparse few cases are under early clinical development in startups. Yet repairing the damage of aging to produce rejuvenation is a minority concern in the broader field, with little support despite its far greater potential. This, then, is the battle fought now, to direct the research community to the far better option rather than continuing in their status quo of working towards the far worse option.

The Geroscience Network is an example of what has come from victory in the first battle of ideas, to generate much greater support for treating aging within the research community. In the past few years things have blossomed to the point at which many influential figures openly advocate for the goal of treating aging, the root cause of all age-related disease, rather than treating age-related diseases one by one. The Geroscience Network was established among those US research groups and institutions whose principals have the greatest interest in treating aging as a medical condition. To quote the pertinent part of their brief:

We hypothesize that by targeting fundamental mechanisms of aging, clinical interventions can be envisaged that could delay or prevent age-related diseases and disabilities as a group, rather than one at a time. By planning and working in a coordinated way through the Geroscience Network, we intend to accelerate development and translation of effective treatments to delay or prevent age-related disabilities and diseases.

Some of the Geroscience Network researchers recently published a selection of open access position papers in the Journals of Gerontology. The papers frame their determination to treat aging, and are focused on aspects of the strategy: how to move forward within the regulatory system, how to undertake clinical translation of potential therapies, how to build clinical trials for this new world of treating aging rather than age-related disease. Notably where specific technologies are mentioned there is little of anything that SENS rejuvenation research supporters would recognize as an effective approach to treat aging, however. The Geroscience Network is the product of researchers who have a slightly overlapping but overall quite different view of aging, which you can find described in the noted Hallmarks of Aging paper, or the later pillars of aging materials. Much of what is seen in those publications as a cause of aging, such as epigenetic changes, looks to my eyes to be a later consequence of the forms of molecular damage described in the SENS proposals. The overlapping areas where the Hallmarks of Aging and SENS agree, such as senescent cell clearance, are to be welcomed where they lead to efforts like UNITY Biotechnology, but it is still the case that more representative examples of Geroscience Network participant projects include the clinical trial of metformin and efforts to develop calorie restriction mimetic drugs, such as the failed sirtuin projects. So while on the one hand it is great to see that the treatment of aging is now well supported as a goal for the research community, it remains unfortunate that the chosen approaches are so very marginal.

Still, there is a clear path ahead for the spread of SENS technologies into the mainstream. That is to demonstrate effectiveness, the old story of bootstrapping enough success on a shoestring budget to obtain greater support from those who were originally skeptical or had their own favored but less effective approach. Senescent cell clearance is the pioneering example here: advocated in the SENS vision for fifteen years, but ignored by the vast majority of researchers. Only in the last five years, since a 2011 demonstration of effectiveness, has more of the research community started to work in this area - and now two startups are working on bringing therapies to the clinic. This example puts the future of SENS rejuvenation therapies squarely on us, the donors, the philanthropists, the supporters. We determine the degree to which SENS succeeds in spreading to the mainstream by our efforts to pull in enough funding and attention to get the research done and the prototypes built. So look at the message of the Geroscience Network researchers with some optimism: yes it is frustrating that they are headed down the wrong road, but they will adopt SENS approaches just as soon as those approaches can be proven in animal studies. Yes, it will be a hard work all the way to the finish line, but when was anything in life easy? In any case, take a look at the papers and see what you think.

Moving Geroscience Into Uncharted Waters

Research into the basic biology of aging has undergone a seismic shift in the last 10-20 years, moving rapidly from the very descriptive approach focused on the aged that was the predominant focus by the end of the last century, to a more mechanistic (and primarily genetics-driven) phase, focused less on describing the aging phenotype in different models, and more on a definition of the molecular and cellular drivers of the process. This progression was accompanied by an evolution in the concepts and ideas that have dominated the field in the past, namely free radicals, cell senescence, and caloric restriction, each of which became the seed upon which the modern foci of research now stands. Progress in a variety of research areas has crystallized into the beginnings of a conceptualization of the process, including seminal publications that described the major hallmarks or pillars of aging.

Aging research is not simply an academic pursuit, it actually holds more promise in terms of helping mankind than most or all other biomedical fields. In terms of health and human suffering, it is well known that four out of five older Americans suffer from at least one chronic disease, and more than half suffer from multiple comorbidities. Aging being the major risk factor for all those diseases, it follows that research into aging could be pivotal in our efforts to reduce the suffering associated with the ravages of old age. In addition to the direct health issues, it has been calculated that care for the elderly currently accounts for 43% of the total health care spending in the United States. By delaying aging even by a lesser degree than currently achieved in animal models, there will be significant gains both in terms of health and wealth. The enormous advances in basic aging research, coupled with the promises described in the previous paragraphs, led to the concept of geroscience, a field that aims to understand the molecular and cellular mechanisms responsible for aging being the major risk factor and driver of common chronic conditions and diseases of the elderly. Of course, there is considerable work to be done in order to bring the field forward and move aging biology towards translation. Major areas in need of further development include, in the preclinical space, the development of better, reliable, and predictive biomarkers, as well as development of metrics for health, including resilience.

Barriers to the Preclinical Development of Therapeutics that Target Aging Mechanisms

An effective preclinical pipeline for developing interventions that target fundamental aging processes could one day transform medicine. However, at the Geroscience Network retreat, it was evident that the best potential strategies for drug discovery and development were not perceived as uniform among those working in the field. In some sense this is not surprising, as researchers have yet to define what is needed to develop a mechanism-based aging therapeutic with clinical utility. Still, the discordance among leaders in the field was enlightening-revealing many unanswered questions and unmet challenges in the discovery and preclinical development of drugs that target mechanisms of aging.

Recent, fundamental advances in our understanding of aging biology have brought the prospects of therapeutic interventions to extend health span and treat age-related diseases and disabilities as a group closer to reality. Despite the growing numbers of promising genetic and pharmaceutical interventions, significant work and financial investment are still needed in order to translate these basic science discoveries into the clinic. To this end, clinical trial strategies relevant to human frailty and resilience must first be established in validated invertebrate and vertebrate models. In addition, standardized preclinical drug development pathways are desperately needed. Some barriers to the clinical translation of therapies that target fundamental aging processes can be overcome by developing new preclinical testing approaches and clinical trials strategies, as well as and funding impediments unique to aging interventions. Together, we must engage in dialog and establish a framework to facilitate the translation of candidate compounds into effective drugs that promote health span and target age-related disorders in humans.

Frameworks for Proof-of-Concept Clinical Trials of Interventions That Target Fundamental Aging Processes

The successful translation of therapies that target fundamental aging processes into routine clinical interventions could transform the practice of medicine and human health. A number of candidate drugs (many already FDA-approved for other indications) have shown promise in preclinical studies. This Geroscience Network retreat developed ideas for proof-of-concept clinical trials that could be the next step in translating interventions that target fundamental aging processes into clinical practice. We described three frameworks for proof-of-concept trials, targeted at age-related diseases, geriatric syndromes, and resilience to acute stressors. Some aspects of clinical trial design are common to all three, whereas some require unique consideration in each framework. Importantly, proof-of-concept clinical trials would serve to test and advance the "geroscience hypothesis" that targeting the fundamental biology of aging will affect a range of age-related outcomes. Trial outcomes would be multidimensional and include outcomes related to the mechanism of action of the intervention; specific to the disease, syndrome, or stress under study; related to off-target effects of the intervention; and broadly relevant to the mechanisms and physiology of aging. Finally, several concrete steps could greatly accelerate the progress of clinical trials of interventions that target basic aging processes, including the development of standardized templates for trial design, toolkits for standardized outcome measurements, the establishment of a national geroscience biobank, and the development of specialist trial and training centers in the Geroscience Network.

Strategies and Challenges in Clinical Trials Targeting Human Aging

Clinical trials that target fundamental aging processes in humans are a novel concept that presents unique challenges and enormous opportunities. Challenges include selection of appropriate study populations, study designs, interventions, and outcomes. We presented two models that conceptualize trial designs for interventions that target fundamental aging processes in long-term and acute settings, defined by extension of health span and resilience to acute stressors, respectively. However, in order to gain the full support of federal and private sectors for development of therapeutics that target aging in humans, it is important to have "aging" or aging-associated outcomes such as frailty, functional decline, and multimorbidity designated as conditions eligible for registration by the FDA. Evidence from human studies is emerging that indicates certain interventions can target multiple age-related conditions simultaneously, potentially by interfering with the aging process itself. With the aging population projected to grow exponentially in the near future, clinical studies that can demonstrate the protective effect of these therapeutics during acute and chronic perturbations in aging humans are more timely than ever. Thus, delaying or preventing the disabilities that occur as a consequence of the aging process would result not only in tremendous cost savings for the healthcare system but also in gains for society on the whole from the increase in productive contributions from older members of society.

Resilience in Aging Mice

Recently discovered interventions that target fundamental aging mechanisms have been shown to increase life span in mice and other species, and in some cases, these same manipulations have been shown to enhance healthspan and alleviate multiple age-related diseases and conditions. Aging is generally associated with decreases in resilience, the capacity to respond to or recover from clinically relevant stresses such as surgery, infections, or vascular events. We hypothesize that the age-related increase in susceptibility to those diseases and conditions is driven by or associated with the decrease in resilience. Thus, a test for resilience at middle age or even earlier could represent a surrogate approach to test the hypothesis that an intervention delays the process of aging itself. For this, animal models to test resilience accurately and predictably are needed. In addition, interventions that increase resilience might lead to treatments aimed at enhancing recovery following acute illnesses, or preventing poor outcomes from medical interventions in older, prefrail subjects.

At a meeting of basic researchers and clinicians engaged in research on mechanisms of aging and care of the elderly, the merits and drawbacks of investigating effects of interventions on resilience in mice were considered. Available and potential stressors for assessing physiological resilience as well as the notion of developing a limited battery of such stressors and how to rank them were discussed. Relevant ranking parameters included value in assessing general health (as opposed to focusing on a single physiological system), ease of use, cost, reproducibility, clinical relevance, and feasibility of being repeated in the same animal longitudinally. During the discussions it became clear that, while this is an important area, very little is known or established. Much more research is needed in the near future to develop appropriate tests of resilience in animal models within an aging context. The preliminary set of tests ranked by the participants is discussed here, recognizing that this is a first attempt.

Comments

A small victory is a victory nonetheless.

Posted by: Anonymoose at August 20th, 2016 12:06 AM

The upside of this democratisation of anti-ageing advocacy, is that now there's room for public debate about which approach of rejuvenation should be favoured (mainstream vs SENS).

Before that, when rejuvenation was a taboo, nobody cared about "petty details" such as the distinction between geriatrics/gerontology/damage repair. That was a time when SENS was completely marginalised and vehemently attacked.

At least now, Aubrey and his team have a better chance to defend and promote their approach - aided in that by the latest encouraging results of their research. The advocacy for damage repair will have a wider impact as it nourishes the controversy.

Posted by: Spede at August 20th, 2016 1:23 AM

That the second battle has still a long way to go is clear from the RB2016 conference. Most scientific talks were about tinkering with metabolism to slow aging. Even worse, the first presentation of the first day said that the *ultimate* treatment for aging is diet and exercise!

Posted by: Antonio at August 20th, 2016 2:48 AM

@Antonio - I don't think exercise/CR mimetic drugs will help people live any longer, but I do think they will help a section of society from eating themselves to death. I know this is already a solved problem, and it is easy to call fatter people lazy, but if keeping the pounds off was simple we wouldn't be heading to an obese majority right now.

At least the whole conference isn't sponsored by Sierra Sciences (telomere elongation) this time!

Posted by: Jim at August 20th, 2016 4:40 AM

Im at least glad to see fund allocated to lifespan OncoSENS and the $15.000 grant. Ive donated $ 550.

Posted by: Norse at August 20th, 2016 6:42 AM

Thanks a lot for your contribution, Norse. I did donate before the grant was announced, so I'll donate again to take advantage of it. I hope other donators will be able to do the same.

Posted by: Spede at August 20th, 2016 8:13 AM

Hi ! I'm a bit angry. Ok a lot.

The other day I was reading about a doctor who was talking about a new drug or kind of precautionary safety advance screening method for brain cancer.
I was very happy for him and his patient, his patient is Gord Downie (the singer from The Tragically Hip rock group from here in Canada), he has
neuroglioblastoma brain cancer stage IV (terminal) and he was told there is nothing that can be done for him (he's 52 years old) as the cancer
spread enough (his doctor said that surgery removed quite a large portion but this cancer is ultra agressive with poor survival prognostic (like 5% survive
for more than 2 years after onset). He was told he has maybe 6 months to a year left of life before he dies. This cancer is ultra deadly because it
metastasize with extreme invasiveness (and of course the most sensitive part of the human body, the brain) and is very 'recurring' or 'surviving';
in fact, it looks like a giant octopus surrounding the brain with long tentacules sprinkles/'sand blasted particules' cancer cells everywhere around it;
how are you suppose to remove it (with surgery) without compromosing the person's brain (lose a large chunk and become vegetative comatose-like zombie)
after surgical tumor-chunk extracted out. Anyways, my point was that the doctor was talking about Gord doing a last show as a cancer-awareness show (people will donate a sum while viewing)
of his own impeding death. This show is today : you watch it around 8 PM Eastern-Time US zone online.
A great thing, indeed. Then, I told myself...
cancer awareness is great, but 'being a doctor that holds on to useless methods' is not.
What I mean by that is that this doctor was almost saying like : ''Please keep me in the business of giving pills or prescriptions to continue
to 'patch up' 'illnesses' and 'allow people to die - slower''....
I was very hurt...I mean here this guy is saying 'let's continue on the 'pills for your ills 'hospital bs'' carousel, and here, on this website,
I read about SENS, SENS IS A f/$%/$%! cure, but no...people will continue to want to 'patch you up' at the hospital and 'make you slowly perish' and
decrepit with cancer alzheimers or what other f&%&?%&?! diseases..sorry for being sensitive...but I lost many people to cancer.
We have TO SOLVE TO F...thing. Not continue patch things..USELESS. DEFEAT AGING. DEFEAT THE DAMAGE - DAMN IT. it's SIMPLE to understand
but assh...will still want their big checks to pay for their BMWs, pools and whatnot (the 300,000$ doctor salary).
The ingrainness of the 'health' attitude is so deep, people like these doctors think SENS is utter BS and damage reversal is useless; or let's say
they look like f...tards when you TRY to explain that to CURE DEATH you must stop damages - and that will ALSO cure to f...diseases TOO.
But no, they want the $$$$$$ over dead bodies.
, hence pharmacies drug stores will continue giving you little shitpills for your Disease - to KEEP YOU ILL AND COMING BACK, UNTIL, OOPS, YOU'RE DEAD.
It's very frustrating this pharma-hospital-doctor establismenth bs. Now Gord Downie will perish, thnks f%$%?$%...

It's Tragically Hip's (tragically..) last concert (you can watch it live free for everyone around the world for those of you who know it/watch Canadian content. For us, here,
he is the biggest Canadian singer and so is passing will mean a lot to us). Sorry again for my temper but dying makes anyone lose their marbles.

Watch it live here/explanations how to :
1. http://www.cbcmusic.ca/posts/12179/how-to-watch-tragically-hip-concert-cbc-aug-20

Thanks !

Posted by: CANanonymity at August 20th, 2016 1:52 PM

@CANanomymity,

Maybe suggest cryonics to him?

Posted by: Robert Church at August 20th, 2016 6:06 PM

@Robert

Hi Robert ! Thanks for that.

I think I will, I just fear that how could cryonics help if the very element at the core of cryonics (the brain conservation) his is problem (brain cancer). Perhaps, a cancerous cryogenized cancerous brain could somehow work, when it would be thawed off in the far future, cancer would resume no matter how long it would be cryogenized - but by then - cancer therapies would be so effective that cancer would be cured, so cancer cryogenizing would work. So it seems woeth it. I don't know exactly the dynamics of cancer cells under cryogenization, if they differ or not at all from normal ones (normally, they shouldn't, but cancer cells don't behave the same as regular ones (and depending on temperature)). Technically, freezing at -196oC renders everything 'dead frozen', it's the freezer liquid vitrification that would allow cells to survive against ice crystallization puncturing destruction of tissue. Truthfully, it's more the public opinion who will laugh at this when it is a solution (will say it's bs, there is nothing we can do, cryonics are still not 50 years there yet, some people were cryonized and the company closed/lost the 'bodies' (they were killed for good) or freezing a dying person is useless). Intact Cryogenizing of the brain is still the biggest obstacle.

Posted by: CANanonymity at August 20th, 2016 7:27 PM

@CANanonymity,

And the alternative?

Posted by: Robert Church at August 20th, 2016 8:09 PM

@Robert

Exactly, - What -..alternative ? There are none...
I mean apart from SENS, there is not much else if anything to do to save this person; all hospital health avenues have been used up
thus it is at the stage of paliative care (When you know there is nothing more to be done with what is available now).

SENS is the only alternative but sadly they don't see that, it seems. It's sad really, it feels like we're 100 years too early for SENS (d*mn it).
I know we are probably not that far but it feels like it when you see people dying around you and it seems a hopeless fight.
But we can't give up, we must continue to hope and support the only solution of SENS. There is nothing else that remotely compares
or approaches to it in its attempt at solving aging and diseases. The rest is exactly what this news talks about of 'The geroscience network'
wanting to continue to 'just slow' the onset of aging by tinkering with metabolism, CR, exercise and 'patch up' pills - dead end avenues.
It almost makes you want to bang your head on the wall of sheer stupidity of it all - it is so Crystal Clear, yet for those in the hospital field
it is so Crystal Unclear (we could explain in 1000 pages to them that it works because that's how life works wouldn't make any difference it would go from one ear and exit the other)
- and they like it that way as the Dough keeps on racking up and bodies at the hospital morgue rack up too. It's a bit like a war dogs, they make money
off war and people fighting each other. Well here, they make money from your decaying hide carcass, they don't give a sh...and laugh all the way to the
bank. It's sad, thanks to greed and capitalism, money can buy anything, even life or your dead body. When these things should be 'a given' and
FREE to everybody - who LIVES. Since, the whole f..point of 'health' 'hospitals' is about 'health', health is connected to aging, aging is connected
to damage accumulation. THey prefer we accumulate damage 'and age' then revert this CAUSAL problem. Because it's 'not ok' to not die, by letting you
continue 'to age' we are 'SURE' you will die - because, after all, we WANT you to die. See self-defeatists mentality (some call it retardation).
If I were to ask them : ''Do you REALLY WANT to DIE ? SERIOUSLY.'' Most would say 'YES' 'but just keep me healthy long enough until I hit the sack at 100!'......
....banging myself on the wall and wanting 'kill' myself from the
utter stupidity (..sigh, it's hopeless). We, Robert, are just the tiny pocket of hopefuls which everyone sees as marginal weirdos who 'believe in fantasy' life extension bs. But, hey, so be it.
Sometimes, I feel like telling them (after SENS is made) : ''SEE, I TOLD YOU. NOW YOU'RE BEGGING ME TO GIVE YOU SENS. GTFO. YOU'RE NOT GETTING IT. You
were spitting at us all along, why should we suddenly be friendly...oh right because we have a moral duty to EVEN help assh..who contributed to death during that time...by hindering the progression of SENS.
You should be lucky we even consider you, you should be on your knees kissing our feet and apologizing forever. F...ash..with their 'it will result in overpopulation' 'life extension is bs' 'SENS is a FUNNY JOKE LIKE THIS BEARDED AdG DUDE' etc...''.
Yeah, that's what I have been reading on every other website and hearing on the street...except here. It's almost like a lost cause, like his brain cancer.
Sorry again for my temper tantrum diatribe but it is hurtful when you do your best to help others (everyone) by creating strategies that will defeat the single most crucial ending thing, dying/death, and people look at you like you're an alien from Mars.

Posted by: CANanonymity at August 20th, 2016 11:34 PM

@Robert

I might I misread your question under the heat/blinded anger of it all :

PS: if you meant, 'and the alternative' in the sense of ''well it's better than nothing, so he should a least try and be cryonized because otherwise the alternative - is death''. Thus he has no other alternative - then to try cryogenics (since the other 'alternative' sarcastically if we call it like that. It's not an alternative, it's an end. But, yes, in a sens it could be seen as an alternative - freeing someone from pain in this life - freeing them from their ending life - to now go to oblivion/paradise/heaven/'the next life'; so, for people who believe in 'that alterative' ok. I don't. I believe in the two alternatives : Cryogenics or SENS. Death doesn'T count as an alternative.

PPS: if you meant what 'other' alternative could there be to 'then cryogenizing the brain specifically'...I really don't know. The only 'non' alternative is Redox modulation, but this must be done early and even then, it's not necessarily sure it would heal everything.
Redox is only a 'do it early (young)' and 'keep it' going (keep young self, that's exactly the same thing as SENS will do (to rejuvenate by reversing damage), Redox modulation doesn't revert any damage - it just avoids it the most it can to post-pone aging (like CR or other metabolism tinkering, the difference is in power. Redox is core protection of the cell, and it has been time and again, the aging is accelerated when redox is lost. Thus, maintenance of redox in young age is the key to long life (for ex: clams maintain their redox for 192 years up to 523 years, it speaks volume of the power of maintaining correct cell redox systems - the redox IS - causal - behind their extreme lifespan, because - by virtue of damage avoidance - redox alters damage accrual - thus chronological lifespan).

Posted by: CANanonymity at August 21st, 2016 12:29 AM

Yea, that is pretty much it, death.

Posted by: Robert Church at August 21st, 2016 1:36 AM

Hi CANanonimity,

Redox modulation is not (to the extend of what I seen) a SENS strategy. I quickly tried to search this web site, but found only your comments citing redox. However I certainly may have miss something as there are hundreds of pages and I do not intent to spend days reading them all.
=> Do you have any comment why redox modulation seems to not be included in SENS?

I see that in Pubmed there are articles about redox modulation agents.
=> Any thought about those agents and their usefulness?

Thanks!

Posted by: JP Le Rouzic at August 21st, 2016 3:11 AM

If I remember it correctly Aubrey De Grey wrote a couple hundred pages long paper on mitochondrial redox in the 90s or early 2000s - I think it's one of the most comprehensive if not THE most comprehensive paper written on that subject and I still see it cited from time to time.
He later wrote a much shorter paper with the bottom line - metabolism is too complex, significant life extension through that path is inconceivable at the moment.
That doesn't mean SENS has given up on life extension through tinkering with mitochondria, as far as I know most of the money they've gotten so far has in fact gone into research on mitochondria, alotopic gene expression and other things in their extramural program.

Posted by: Anonymoose at August 21st, 2016 3:31 AM

Thanks Anonymoose,
I think CANanonimity speaks about redox at cell level. But indeed both are interesting.

Posted by: JP Le Rouzic at August 21st, 2016 4:59 AM

@CANanonymity : "Sometimes, I feel like telling them (after SENS is made) : ''SEE, I TOLD YOU. NOW YOU'RE BEGGING ME TO GIVE YOU SENS. GTFO. YOU'RE NOT GETTING IT. You
were spitting at us all along"

I know how you feel. The same kind of thoughts are running through my head. Resentment for the lack of vision coupled with a wealth of contempt.

Posted by: Spede at August 21st, 2016 8:58 AM

It's really sad what's happening to Gord Downie. I think his only choice is cryonics. You don't need to worry about cancer at liquid nitrogen temperatures. Chemical reactions that take 1 second at room temperature will take 25 million years at -196ÂșC, by Arrhenius equation.

Posted by: Antonio at August 21st, 2016 9:18 AM

@JP

Hi JP! Thanks for that.

Sadly, redox has evaded most research. Not saying there is none on it, there are plenty. But it
has evaded 'follow up', apart from glutamate cysteine ligase overexpression and a couple of other tricks,
they have not been capable of - seriously - altering the redox. It is very tight ship (tightly controlled by cell),
so it's sad but I keep hoping on it but there is now barely no more research 'follow up/development/action' on it.
Yet, you can find new research that repeat that the redox is important (we know that already from last 30 years).
Like there is was this one or two studies recently that definitely caught my eye and was quite revealing,
but, alas, it will sleep in the dust bin and get no further 'doing something about it' action :

Erythrocyte Plasma Membrane Redox System May Determine Maximum Life Span
1. http://www.sciencedirect.com/science/article/pii/S0306987710005268

Modulation of Erythrocyte Plasma Membrane Redox System Activity by Curcumin
2. http://www.hindawi.com/journals/bri/2016/6025245/

The redox modulation agents (such as curcumin up there) are a mix-bag, mostly, in the long term, useless sadly.
In the short term, though, definitely are worth it as they do alter the redox positively and this has great
effect over a short period of time - but for very long time (like a life) they are pointless : because
most of them alter glutamate cysteine ligase, by altering GSH efflux (glutathione efflux by altering gsh transporters)
or they accelerate GSSG -> GSH recycling by GSH reductase overactivation (thus alter oxidized thiols pools).
Plus, most of them alter the main redox enzymes sensors (Thioredoxin, glutaredoxin, peroxiredoxin). But, the problem remains,
when you age most the enzymes become dysfunctional (they accumulate mutations and damage too), they can even become pro-oxidizing
rather than keep the reducing potential of the redox. As such trying to alter the GSH:GSSG ratio becomes very difficult,
even with adding GSH alone itself or in other forms (such as NAC, GSH-ethyl mono ester, Whey (contains the tripeptides blocks),
even adding the precusor tri peptide amino acid themselves : Glutamate, Cysteine and Glycine (which compose GSH). The problem remains
that if one 'aged/old' redox enzyme is 'wacked out', it can have dire consequences on the overall redox
(it's an extremely tight-ship/finite balance (measured in mV (reduced potential)). As such, you see failure
when, for example, they try to add GSH or redox modulation agents, and they fail to - maintain - the redox to its original state.
Like one study showed they added GSH to a frog and verified the effect on the frog's lifespan. There were three frogs, one sick with
accelerated aging, one normal healthy and one control. The normal healthy one and the sick one both received GSH for their whole life.
They both did not live above specie MLSP, but both have 'substantial' increase in 'mean/average' lifespan and their 'chance' to reach
their MLSP was 'greatly' increased (meaning GSH allowed the frog to reach its utter maximal lifespan of its specie, 7 years).
But here's the kicker : at around 3-4 years, the frog's brain GSH content did not respond anymore to GSH supplementation.
Meaning ther were no more elevation, it demonstrated that the old frog's brain was starting to have unresponsive redox enzymes
(especially the most important one, glutamate cysteine ligase was like 50% less active, as such of course the levels were dwindling
even if there was supplementation, and also gsh transporters - would also be slower - thus a 'GSH carrying to cell' problem.
It's very frustrating because it's the most incredible thing yet we can't do much about it right now. Still, it's not a totally
dead end avenue just yet.

@Anonymoose

Hi Anonymoose ! Thanks for that too.
Yes, exactly, these reasons are too why redox gets left out.

@JP
Yes JP, it's both extra-cellular and intra-cellular, including crucial mitochondrial redox I was refering.
They are very complex and have their differences. But all of them together compose the redox large.

@Spede

Hi Spede ! Thanks for sharing that...exactly.

@Antonio

Hi Antonio ! Thank you for these words... It really is...
On cancer being dead frozen by temperature slowing chemical reactions to near eternity : That's a good thing !
I think then, you're very right, cryonics then because of feasability for him (he has accumulated certain wealth,
what to do with it ? if he dies rich of cancer it's pointless, it's better for him to place his money towards
a 'chance' to perhaps be cured of cancer in far future, by cryogenizing. The real question that he should ask
himself is this :

Should I cryogenize myself - living - right now, while I'm still 'alive' ('alive body' cryogenization) before my
cancer kills me soon. Or should I have my 'dead corpse/carcass' be cryogenized once I'm dead by my cancer ?

(In first case, he would be 'reanimated' upon being thawed in the future, his cancer would 'continue' its course
immediately, but he could have access to a cancer cure immediately too - thus, effectively, curing his cancer in the short timeframe he would have
upon being thawed and cancer resumes its progression (since the cancer is frozen - with him).

(In second case, he would 'have' to be reanimated somehow, they froze a (alreadly long) dead body. Perhaps, there would be
technology that could reanimate dead tissues should he have sufficient remaining tissue (we have to understand that after
technical 'death' the body cells continue 'living' for a while and the process of putrefaction (aerobic and anaerobic bacterias eat flesh from intestinal flora)
goes on/same for loss of cytochrome c in the cell mitochondrias (cell mitochondrias litterally commit suicide by losing their cytochrome in massive orchestration)...
As such, if there is enough still decaying 'flesh', it could be revived/reversed by therapies in the future (effectively 'Reversing death' Reanimation of dead cadaver)

Posted by: CANanonymity at August 21st, 2016 8:32 PM

@Antonio

PS: When I meant 'should I cryogenize 'alive' while I'm still alive'...I meant that - obviously, if he cryogenizes alive it's way better than cryogenizing himself - dead. But there is a fear to it...like cryogenizing a 'living' human is very scary...still not scarier - than death itself I think (since he faces this prospect soon from his cancer Killing him). So, he should really 'freeze while 'still' alive for a couple more months before cancer gets him'. But people will object to 'freezing a 'still alive (he's not dead - yet - by his cancer)' human - when it's very stupid . He will die - Anyways so what does he have to lose ?
Freeze me away - Live/Living - before I'm - really - dead.

It is scary to 'freeze' a Living Human, but this man is almost dead and Will die, so this is a very different story than picking some random healthy person on the street and freezing them on the spot (ethically wrong and almost like 'killing' someone since you stop them from living, by freezing them.
In his case, he will stop to live - anyways, by his cancer, makes no difference since his life is already ended. It's a 'chance' to give him to perhaps have his life back - in the future.

Posted by: CANanonymity at August 21st, 2016 8:52 PM

@CANanonimity: Thanks for the long and detailed answer. I will think about it. It is something I never read elsewhere and it looks very interesting.

Posted by: JP Le Rouzic at August 22nd, 2016 12:14 AM

Is it really (legally) possible to cryopreserve alive ?

Posted by: Martin S. at August 22nd, 2016 2:07 AM

It's a bit of a moot point really considering cryo is illegal in Canada. Or some candien provinces anyway.

Posted by: Anonymoose at August 22nd, 2016 3:47 AM

Anonymoose: Only in British Columbia.

Posted by: Antonio at August 22nd, 2016 4:20 AM

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