Gearing up for the war on aging

The stage for this blog entry was set by the recent one If we can multiply lifespans of nematodes by seven, why have we not been able to get anywhere with significant human lifespan extension?  The way things are going it is highly unlikely we are going to see a radical upward increase in human lifespan for many years.  I asserted that perhaps, if we are very lucky, we will see a 15% increase in expected human lifespan for people who follow certain interventions within ten years.  But there will be nothing approaching the lifespan increase of 60% or more that we have seen to be possible in mice.   I have laid out the reasons progress in anti-aging science and practice is likely to be slow and incremental for the next 15 years or so.  Unless, that is, we can manage to launch a War On Aging.  Such a war is what this blog entry is about.  I deal first with how to justify such a war, second with what such a war could look like, and third, steps to getting the war started.

Justifying the War On Aging

There will be no War On Aging (WOA) unless there is a massive transformation in the perceptions of the public about aging, the great benefits of waging a War on Aging, and the costs of not waging such a war.  A massive educational campaign is needed to get the following points across and embedded in everyone’s conscience:

1.      A war on aging is winnable. Significant extension of human lives is possible.  We have multiplied the lifespans of lower animals and we can do it for us humans if we put our minds to it and our resources behind it.

2.     The result will increase health and decrease health care costs.  Lifespan and healthspan go hand-in-hand, so we are talking about people having lots more healthy productive years, not about expensive interventions to keep very-sick people from dying.  The result of victory in a WOA will be an increase in the ratio of healthy productive years to infirm unproductive years.

3.     The war would produce an immense increase in national wealth.  In a highly complex post-industrial world, human capital is the most important resource representing trillions of dollars spent on education and work experience.  Keeping that educated and experiences human capital around and working 10, 20 or more years represents trillions of dollars in conserved national wealth.

4.     Enormous productivity and economic benefits could be realized.  The result would be an immense increase of productivity and economic benefits due to healthy experienced older people working longer.  An increase of healthspan of only 10 years would not only cut healthcare costs immensely, but also produce more than enough trillions of dollars of productivity benefit to wipe out our national debt and put our economy into the black.

5.     It is the right war to fight.  We have been spending hundreds of billions of dollars a year on wars on diseases of aging like Alzheimer’s disease, cancers of aging and Parkinson’s disease.  And we have mostly not been winning those wars because we have not been attacking the root cause which is the aging process itself.  If the war on aging increases healthspan by 15 years, the average time of onset of all diseases of aging will be postponed 15 years.  For a massive increase in public health, the WOA is the right one to fight.  

6.     It is a war that can impact directly on you and your family.  Victories in this war can keep you and your loved ones around and healthy for many more long years.

7.     The war does not have to be that expensive.  I venture to guess that a properly-organized NIH budget for the two WOA missions I described below that builds up to around the $600 million level in 3-4 years and stays at that level would probably produce significant results within 7-15 years.  This figure is under 2% of the NIH total budget.  “The NIH invests over $31.2* billion annually in medical research for the American people(ref).”  

What the WOA would look like

The War on Aging (WOA) will have to be a partnership of the media, academia, government, the health care industry and biotech/pharmaceutical businesses.  Each of these would play important roles, not-for-profits and government in the earlier stages, businesses in the later stages.

The aging-research programs funded by the National Institute for Aging (NIA) and organizations like the Ellison Medical Foundation have produced valuable results and mostly merit continuation.  However, these programs are primarily basic-research oriented and do not have human longevity as a goal.  Human life and healthspan extension is not part of the mission on NIA and must be the  first and foremost goal in whatever government organization takes the lead initiative in the WOA.  Mission-oriented programs with time-specified objectives are required such as those at NASA.  For example, I suggest two such mission-oriented programs here.

The 20% life extension mission – 8 years to full public availability

–       The target objective of this mission is to establish reliable and safe interventions to increase human lifespan by 20% – so that instead of expected lifespan being around 80 as it is now in the US, it can be expected to go up to about 96 as the fruits of the program are realized.  There should be a targeted average increase of at least 15 productive years for members of developed societies who benefit themselves from the interventions of this program.

–         The focus of this mission is not so much on new basic science breakthroughs as it is on providing safe “engineering solutions” for limited lifespan extension.

–         This program would focus on interventions affecting known longevity pathways and genes where there is already a significant base of science and animal experimentation: mTOR, IGF-1, SIRT-1, human counterparts of INDY in fruit flies and DAF-2 in nematodes, etc.

–         Within 5 years, starting with mouse and working up to simian models, establish the science and probable feasibility of 20% lifespan extension in humans.   Determine the best combination of interventions to achieve this objective.  Favor non-invasive lifestyle, nutritional, and natural-supplement interventions to the maximum extent possible.    Conduct programs to also establish the safety of the interventions in simians.

–         It is too soon to say whether stem cell or epigenomic interventions will play a role in this mission.

–         Dietary supplements like curcumin and resveratrol may play a role in this mission as well as drugs, but drugs are likely to be ones already in existence or under development, e.g. SIRT1 activators, rapamycin analogs or metformin.

–         In the third year of the program adjust the lifespan target for the Mission upwards (to 25%) or downward (to 15%) depending on research progress.

–         By year 7 of the mission, have established the safety of the anti-aging interventions in humans and have developed biomarkers of efficacy.  If regulatory hurdles are in the way, ways around them must be discovered.

–         Within the next year – 8 years total –products  and lifestyle regimens for humans  will be on the market with probable capability for extending lives by an average of 20%.  The 20% figure is a rough aggregate.  Probable life extension would not be the same for everyone and would vary depending on health and genetic makeup of the individual, age when the interventions are initiated, and lifestyle factors.

I have no way to prove it, but I strongly suspect that the current anti-aging lifestyle regimen and supplement regimen together may already have the capacity to extend average human lifespan an average of 10% to 15%.  So I see a 20% average extension within 8 years as an objective that is quite possibly within reach given all that is already known about aging pathways and already-available interventions.

The 60% life extension mission – 15 years to availability of longevity products

–         The aim of this mission is to establish strong feasibility for extending human lifespans by 60%, and to do this so that interventions aimed at this objective are available to the public within 15 years.  If the program is successful, the average human lifespan maximum for those benefiting from the intervention would go up to about 128 years, with good healthspan of over 115 years, maximum human lifespan of about 190 years.

–         This 60% lifespan increase program can be run in parallel with the program designed to produce 20% lifespan increase and both programs can benefit from what is learned in the other program. 

–         The program for this mission will require a hefty research component as well as a daunting subsequent engineering component.  It will require new kinds of interventions beyond those in the 20% lifespan extension program.

 –         Stem cell science is likely to play a major role in this mission, probably based on perfection of technologies for creating reliable high-fidelity autologous induced pluripotent stem cells (iPSCs), learning how to get them to differentiate into any tissue desired, and developing a host of therapeutic approaches for using them.  A news item appeared yesterday signaling an important new breakthrough in iPSCs and I will explore the ramifications of this development soon in another post.  I have a lot of faith in the longevity potential of closing the loop in the stem cell supply chain.  See my blog posts IPSCs, telomerase, and closing the loop in the stem cell supply chain,  and The stem cell supply chain – closing the loop for very long lives. Also the discussion in my treatise of the Stem Cell Supply Chain Breakdown theory of aging is applicable. 

–         Another stream of technology that could figure heavily in this mission is epigenetic regulation of longevity genes.  See the discussion in my treatise for the Programmed Epigenomic Changes theory of aging.  I expect to produce a new blog entry soon with up-to-date news on research on epigenetic regulation of aging.  Also you could review my 2010 AAAS presentation Towards a Systems Theory of Aging.

–         In the earlier stages, all research will be on animals to establish feasibility, starting with mice and working up to pigs and simians to establish safety and efficacy.  There can and should be human trials for safety of interventions but it obviously will take many decades to establish the degree of efficacy in ensuring such long lives. 

–         Like the 20% mission, this mission would probably not countenance use of genetic interventions such as knockout of genes or insertion of multiple gene copies – the kinds of interventions that have led to significant life extension in lower species.   The social environment would have to be prepared to allow even experimental genetic modifications of humans, and I don’t think that is possible in the near future.  Ethical, moral and religious scruples would have to be dealt with, and an enormous controversy could ensue making the present battle over using embryonic stem cells seem like an outpost skirmish.  That controversy could kill or hobble the War On Aging before it even gets started. 

–         I think it both highly desirable and possible to sidestep such a controversy and achieve the goals of this mission without altering human genes.  We probably don’t need new human genes or to get rid of existing ones to extend lives by 60%.  We just have 1.  To develop safe and reliable means for turning certain of our existing longevity-related genes off and on and/or 2. Develop a means for continuing renewal of human cells with aging.  Again, the preferable approaches would involve use of induced pluripotent stem cells and epigenomic manipulation of activation and silencing of selected longevity-related genes.

–         We will need different ground rules for human experiments than clinical trials to move along with this research.  The time frames and costs of clinical trials and the need to cloak them as trials of medical interventions would slow research so much as to make a 15-year goal for this mission impossible. 

–         If there is to be a third future mission in the WOA with objective to double human lifespans, however, at that point the issue of human genetic alterations will have to be squarely faced.

Social aspects of the war on aging

Significant social changes will be required if the WOA is to be successful making the social engineering of life extension as important as the biological engineering.

–         If people are to live, say, 16 years longer and are expected to work that much longer, there needs for increasing emphasis on lifetime learning, on work as opportunity for self-fulfillment and play, on the contributions older people are uniquely qualified to make, and on the multiple adventures life can offer.  There will be no productivity benefits to longevity if people at 55 or 65 continue to move to Florida where they will live in retirement communities, play bridge, golf and bingo and live their extra years in general boredom until they finally die.

–         As longevity increases, so will the general business retirement age and the social security retirement age have to be raised.  The message is not just “you have to work a lot longer.”  Simple economics says that if people work longer, they should be able to retire with more money.   

Getting the War On Aging started

Like all wars, the war on aging will have to be concertedly and skillfully sold – sold to policymakers and to the public  – and this is a matter of communications, media and social organization not a matter of scientists talking to other scientists.  The two usual major selling points for wars have to emphasized:

–         Absolutely terrible things will happen if the war is not fought.  This one is easy.  A hundred million or more US citizens will die prematurely if there is no War on Aging.

–         There is a large payoff to the war, and the war is the right thing to do.  This one is also easy, just looking at the economic benefits involved.  And think of how wonderful it will be to keep your parents and grandparents around and healthy so much longer.

In other words, the moral high ground goes with fighting the war.

So the messages required for starting a WOA are fairly clear.  The key questions is “Who will deliver these messages to whom in a way that gets things going?” and here the situation is very murky.  For now, I will share a few general ideas:

–         The arena for selling the War on Aging is the public media, not the scientific literature. 

–         Before the WOA can be started as mission-oriented programs, the possibility of WOA must be started as a broad dialog among leaders from every sphere including economists, social scientists, politicians, community leaders and religious leaders.

–         Getting major TV exposure for the concept of WOA will be very helpful for getting the dialog going.

–         It would be also very helpful if prestigious life-scientists came out of the closet and supported the idea of a WOA.  We need TV showcasing of Methuselah mice.

–         It would be good for a high-profile science series like Nova to do a series on life extension.

–         Emphasis needs to be put on the points listed above: the economic benefits of fighting the WOA; the fact the war can be won; how this war gets to the root causes of a lot of other expensive wars we are fighting  against the diseases of old age, and the personal benefits of longer lives.

–         It would be helpful; if there were more high-profile studies by economists that quantify the economic value of life extension by 10, 20 or 30 years

–         It would be very helpful if some visionary foundation put its resources behind starting a War on Aging.

–         A good first step would be a high-level conference of policymakers, economists, scientists and political leaders examining the prospects for a War on Aging.

I plan to return to this topic.