Endorse the best Life-Extension treatment

You are presented with a selection of technologies on which much has been written about in terms of how they could extend human lifespan.

You are invited to vote your choice as to what you believe is the technology that offers the most promise in treating aging and providing the most longevity enhancement today.

When casting your vote please try to take into account:

1) Supporting studies (evidence of anti-aging function)
2) Means by which the intervention could be administrated in humans (oral, recombinant viral, etc)
3) Length of time to bring to market (how mature is the technology)
4) Estimate of lifespan increase as a result of treatment if intervention begins at 40

You will note that Nanotechnology is not an option since at present this technology has not matured sufficiently to have any studies associated with life extension applications.

If you can, please offer an explanation as to why you chose the technology you endorsed.

Enhanced Anti-Oxidant Production - mitochondrially targeted

1) exogenously applied, ie. Mito-Q
2) endogenously upregulated through pharmacological means, ie thioredoxin upregulation

both of the suggestions above are in process. Mito-Q is being developed for treatment of mitochondrial disease Freidrich's Ataxia while Richard Cutler with Kronos Longevity is working on pharmacological gene therapies and has made some promising progress (unpublished).

Either of these technologies used in mice would demonstrate proof of principle and provide substantial impetus for the development of other technologies. In Richard Cutler's words,

"t is likely that within 3-5 years we will have something that will extend human lifespan 3-5 years".

This could be overly optimistic, but oxidative stress is definitely where a lot of the research is being done and where I believe the 'low hanging fruit' will be discovered first. More challenging technologies will begin to be seriously looked at when the more accessilbe technologies provide reason to develop them.

Kevin

You will note that Nanotechnology is not an option since at present this technology has not matured sufficiently to have any studies associated with life extension applications.

Nanotechnology should be viewed as an enabling technology. Major investments and funding is being placed in development of biomedical nanotechnology. That is, making tools to help research into biomolecular systems. I agree that nanotechnology is not being directly investigated as an anti-aging technology, but it should still be used as a research tool into anti-aging.

The reason nanotechnology was not included:

I can say that there isn't one person here that is not anticipating the technological revolution that nanotechnology has been promising since 1995. Unfortunately it has largely been hyperbole and as of today, aside from numerous theories there is no evidence of any practical application relating to life-extension applications. This is why it has been left out as a voting choice. The choices relate to technology that could be implemented at present.

Here is a link from the original Wired article back in 1995. It is almost 10 years later, and not one of the categories predicted, including Molecular Assembler, Nanocomputer, Cell Repair and Commercial Product, has yet even remotely been achieved.

Considering that this is the technology on which the validation of present cryopreservation techniques is reliant upon, it is disconcerting.

Kevin, I think you're on the money with MitoQ. It will probably be the first to market. Out of all the choices, though, I don't know if it represents the treatment that would give the most life span extension.

Lightowl, have you chosen? I am interested to hear the opinion of an engineer. Nanotechnology does not count for this poll.

With few exceptions (brain cells, etc) most cells in the body divide, degrade, and are replaced with regularity over time. So, I choose 'Stem Cell Proliferation & Migration' with longer-term 'DNA repair'.

Stem Cells are already showing effectiveness (heart muscles) as a minimally invasive way to treat some age related diseases... while DNA repair looks to be a longer-term way of maintaining tissue 'youth' by tackling the root of the problem - DNA code.

Stem Cells carried out further, can also be used to replace whole organs.

Mike West, CEO of ACT, has done good work toward these goals: http://imminst.org/f...&f=13&t=2014&s=

With my limited knowledge about biology I would tend to take the Enhanced Antioxidant Production. But I can not with any certainty explain why that approach would be any better than the other ones. I think the accumulation of mutations and toxic elements should be the immediate focus to extend life and prevent disease.

On the nanotech thing. It is not entirely true that there are absolutely no commercial products on the market today. Most are still research tools, but some are available to the public. Also, many are in the pipeline and has been proven concepts for some time. http://www.smalltimes.com has a good collection of articles explaining which and when they will market. In fact, most new cars sold today has some elements of nanotechnology incorporated in them. Nanotechnology is an enabling technology that will improve current products as well as create new products. In the next couple of years you will se nonvolatile memory (NRAM) and very cheap mass produced solar panels hit the market. Nanocomputers are already being produced. 65nm ship sets. I am surprised you have not been following the nanobiotech sector more closely. There are some important breakthroughs in that sector.
http://www.foresight...edArticles.html
http://www.nanobiotechnews.com/
http://nanotechwire....ews.asp?nid=753

Solar-cells are going strong to.
http://www.technolog...fairley0704.asp

Edited by lightowl, 22 July 2004 - 06:47 PM.

My personal view on this is that DNA repair/maintenance (DRM) types of interventions will provide the most substantial reduction in the rate of cellular aging more than any other technology (including the SENS proposals).

We have an enormous amount of studies now, ranging from cell culture to model organisms to individuals that suffer from premature aging syndromes as well as from normal aging individuals, that implicate DNA repair failure as the nexus of abnormal cell behavior leading to senescence, cancer or death. In all of these studies we have seen the effect of insufficient DNA repair. To provide complete proof of this hypothesis, however, we need to observe what effect DNA repair enhancement will have on aging. Thus far, cellular studies indicate that where specific DNA repair associated enzymes have been overexpressed, ectopically expressed or transfected from other organisms to enhance DNA repair, the cells have experienced an increased resistance to the rate of DNA damage and consequently had increased lifespan.

The mode of administration of such a treatment today would be via intravascular injection of non-infective vectors designed to primarily target specific tissues such as brain and heart, followed by peripheral tissues. The aim being to get the vector into as many life critical tissue types as possible. The vector contents would include multiple copies of long lived plasmids designed to encode the genes and respective organelle targeting sequences of specific enzymes designed to enhance DNA repair and maintenance. Such a treatment would have to be repeated every few months.

Considering that efficacy studies could be started in drosophila (6 months), then moved to senior mice for refinement (3 years), followed by human safety trials (3 years) in discrete tissues, followed by human efficacy trials in global delivery (2 years) such a treatment could be brought to market within 6-8 years.

DNA damage is the major cause of cell death but not the only cause. Also we don't know if cells can become rejuvenated or just slowed down in aging from enhanced DNA repair. Clearly once a cell is senescent, enhanced DNA repair may not help it. What we do know it that the rate of cancer should dramatically drop as should the rate of apoptosis resulting in a substantial drop in new disease irrespective of age. The earlier such a treatment starts the potentially longer the lifespan. Considering that the innate regenerative capacity of the body whilst in decline continues until well into old age, slowing down the rate of damage would presumably allow regeneration to catch up.

I suppose we shoud clarify what we're voting for. Are we voting for the treatment we think will be most effective? The first one to market? The most band for the buck (or for the time to market)? In other words, if I think it will take 5 years to bring one treatment to market that extends life 5-10 years, and it will take 10 years to bring another treatment to market that extends life 20-30 years, which one are you asking me to vote for? Or do I decide the criteria?

Jay Fox

read the first post - offers most promise based on technology available today

My vote would have to go for calorie mimetics specifically sirt1 expression thats being spearheaded by Leonard Guarente.
SIRT1

Mainly because it looks like it would already have a large market (anti-obesity) to provide funding for it to get to market. From there I'd expect that clinical trials would show improvements in the aging phenotype and aging related diseases. From what I have read all the supporting studies on organism models have not contracted its beneficial effects.

I am not sure exactly what the form of the mimetic would take but I am guessing drug form is possible.

Although improvements would probably be of the order of 10%-20% it does seem like the closest one to actually being available.
I would put a timescale on this one of 5-10 years as there are quite a few teams working on this (but maybe I being too optimistic).

Ames dwarf mice on CR show cumulative life extension effects. CR mimetics and insulin receptor inhibitors.

How longer do you think we could live with MitoQ?
Why does noone here seem to be intressted in the mechanism of progeria. If it could be understood there is a chance that even normal healthy people could benefit from a possible cure.

The accelerated degenerative aspects of Progeria are important and we have a few threads dedicated to that research. BTW Wolfram, Werner syndrome is another name for Progeria.

Werner Syndrome and Aging Genetically Identical
http://www.imminst.o...&f=44&t=1883&s=

There are other threads too and please feel encouraged to pursue this area and contribute if you feel it is lacking sufficient attention. There are now eleven pages of threads on Biotech alone and I would suggest reviewing some of the ones focused on what we have learned of the genetics of aging, to include the thread on the current Theories of Aging:
http://www.imminst.o...&f=44&t=1153&s=

After that review the discussion of your questions may be more fruitful.

I would add that I tend to see the problem as a strategy versus tactics dilemma, especially when one perceives the problem from different perspectives based on one's current physical age.

Those of us in the latter stages of physical maturity are going to be more focused on extending our *current state* long enough to be offered the possibility of more serious reversal opportunity and those who are younger might be more focused on techniques that *only* slow aging and prolong existence.

There is a distinct tactical advantage to *stopping* aging as opposed to merely *slowing it down* for many boomers and it is from *boomers* that the majority of funding for research is going to come from.

Logically the long term strategy is to find a means of *preventing* (and stopping) aging after key developmental phases, as well as to be able to reverse damage back to a desired physical stage but rational tactics based on *current* technology for a *The War On Aging* require that some hope for survival of current combatants be developed. This approach means that a more demonstrable prophylaxis be developed and I also think that MitQ offers that but really it is only a matter of *buying time*.

If the time this process offers (IMHO decades at the least) is not used to great advantage then it is seen as merely a delaying tactic in our War On Aging.

Mr. Lazarus I seem more informed than you about progeria so i suggest that you read more about it so it would be more "fruitfull" to discuss with you...

Hutchinson-Gilford syndrome wich is populary called Progeria is caused by a deletion mutation i Lamin A. Werners syndrome is caused by a mutation in a helicase. Werners is a progeroid syndrom but it is NOT the thing you call progeria. Werners patients die at age ~40 Hutchinson-Gilford patients die at age ~10.

The most imortant thing with something like MitoQ would not be that it acctually makes us live so much longer but that it would open up the minds of people so that they would see that anti-aging intervention is acctually possible.

An excellent point and distinction but instead of seeing this as some silly competition proceed to include more information. That was my point to begin with not to engage in a debate.

Did you read the links I referenced above?

Please feel encouraged to go to them and bring them to the front with more discussion and references. Consider this s self serve forum and as long as the links you use are from reputable sources and check out you're encouraging the discussion you seek and contributing to educating us all.

You are correct on the distinction between Hutchison-Gilford and Werners though both were considered forms of progeria till more recently. The genetic distinction you are referencing is a relatively recent development that I am glad you are contributing to.

Now can you extrapolate a relationship between the two different genes and why they separately contribute to similar but not the same result?

We are a discussion group more than a straight Q&A group. Imminst isn't like WebMD where you go to get all your answers as much as background as you are suggesting on asking better questions and then contributing to a broader and better collective understanding by friendly discussion. I do not think debate is always necessary for that and I was encouraging you to resurrect the topics and contribute to them, not trying to debate you. Feel free to add more too.

I am very glad the topic intersts you and I am hoping you share this interest with us all.

Mr. Lazarus thank you for the links, but I was not looking for a popular description of Hutchison-Gilfords or aging theories, becouse I have read similar papers many times. I was looking for a description of molecular mechanisms by which the deletion mutation in Lamin A causes the symtoms seen in the patients.
Only with the understanding of the mechanisms can we think of a possible treatment for the patients and maybee for healthy people as well.

Here are some papers which could be usefull I hope you find them interesting:

----------------------------------------------------------------------

"Towards a unified and interdiciplinary model of ageing"

Abstract: http://www.ncbi.nlm....t_uids=15193354

Full Text: http://www.sciencedi...3edfa77f4f747e8

Pdf: http://www.sciencedi...4d7b94&ie=f.pdf


-----------------------------------------------------------------------

"Aging and nuclear organization: lamins and progeria"

Abstract: http://www.ncbi.nlm....t_uids=15145358

Full text: http://www.sciencedi...abedf217e5a003b

Pdf: http://www.sciencedi...f029a2&ie=f.pdf


---------------------------------------------------------------------

"Fibroblast clones from patients with Hutchinson-Gilford progeria can senesce despite the presence of telomerase."

Abstract: http://www.ncbi.nlm....t_uids=15050279

Full text: http://www.sciencedi...0474e762d8f185d

Pdf: http://www.sciencedi...f029a2&ie=f.pdf

-----------------------------------------

I can see the reason for your enthusiasm in investigating mutations in nuclear lamin which result in an inability of the nucleus to export mRNA. Effectively it would be like shutting down all nuclear gene expression! Consequently it comes to no surprise that telomerase would have no effect on senescence in cells with this mutation.

Do you know how this mutation becomes induced in non HGPS types of disorders? According to the first article this is a progressive condition typified by all aging cells and I suspect that it would be associated with alterations in gene expression. From an evolutionary standpoint this could be an adaptation that functions to gradually quieten the cell nucleus from expressing mRNA as regulation of gene expression becomes progressively more bizarre.

What I also found of interest in the first article you cited is the reference to cellular response to damaged histones by degradation. Such a response as you can well imagine would have an enormous impact in altering gene expression by unsilencing DNA if it is not immediately repaired.

Incidentally, the way to deal with such a single gene disorder, either inherent or induced would be via gene repair which is not the same as DNA repair, which refers to the endogenous ongoing mechanisms of DNA maintenance, but of the technique of replacing a flawed segment of DNA with a desired one.

Targeted gene repair -- in the arena