The Mission Impossible of Genetic Redesign For Longevity
Permalink | View Comments (9) | Post Comment | | Posted by Reason

If you had to pick the absolute hardest, most challenging goal possible in biomedical science, I think it might be to alter the genes of adult humans so as to safely extend healthy life. Yet this is pretty much the course of the mainstream aging research community - and so I believe they are setting themselves up for maximal expense and minimal progress:

It is their belief that this is the only practical way ahead: a laborious slog towards complete understanding of aging and metabolism, followed by an even more complex navigation through re-engineering that metabolism to age more slowly. The sheer scale and difficulty of that task is why many scientists feel that meaningful engineered longevity - more healthy years through science - is a long way away indeed.

Here's a paper restating that point:

Studies performed on various experimental model systems indicate that genetic interventions can increase longevity, even if in a highly protected laboratory condition. Generally, such interventions required partial or complete switching off of the gene and inhibiting the activity of its gene products, which normally have other well-defined roles in metabolic processes. Overexpression of some genes, such as stress response and antioxidant genes, in some model systems also extends their longevity.

Such genetic interventions may not be easily applicable to humans without knowing their effects on human growth, development, maturation, reproduction and other characteristics. Studies on the association of single nucleotide polymorphisms and multiple polymorphisms (haplotype) in genes with human longevity have identified several genes whose frequencies increase or decrease with age.

Whether genetic redesigning can be achieved in the wake of numerous and complex epigenetic factors that effectively determine the life course and the life span of an individual still appears to be a 'mission impossible'.

Not impossible, just far, far harder than the alternative - which is to avoid changing human genes and metabolism, rather aiming to repair the damage of aging in the biochemistry we have today, thus reversing the effects of aging. That goal allows us to skip over a great many things we don't understand about human biochemistry and avoid many challenging endeavors - and it will produce more valuable and effective therapies into the bargain.

Why take the hard path to extend longevity a little by slowing aging when there is an easier and more direct path towards reversing aging? The debate over the approach to aging research in the next few decades is vitally important to progress in engineered longevity: the presently dominant strategy is an inefficient path forward, and it will eventually produce therapies that do little to help those of us who have grown old waiting for them. That has to change.

Comments

Isn't such extension of life essentially robbing resources from the younger generations, diluting their precious "time under the sun", tilting society toward the old, infertile, and undynamic, and away from the opposite?

Posted by: e at November 16, 2008 5:47 AM

No. I think you are confused as to where resources come from and how wealth is created. It is not a zero-sum game, and people are net producers of wealth. More active, healthy people living more active, healthy years means more work is taking place to create wealth for all. See:

http://www.longevitymeme.org/articles/viewarticle.cfm?article_id=9

and

https://www.fightaging.org/archives/001419.php

Posted by: Reason at November 16, 2008 8:25 AM

There is some revisionist evidence that the "population explosion" of the late 20th century was an illusion. Fertility has been dropping since at least WW2, while infant mortality had a one time dramatic drop with the development of antibiotics and better natal care. The result was that population went up and now will start to drop.

We will need workers - all over the world. The self-centered "young" aren't going to be numerous enough. There are going to be two possible sources: immigrants or older people. Europe is taking the first path; we (look at Wal-Mart) might be considering the second. That approach has its advantages - chiefly the large information base that already exists in older brains. It is a matter of enormous economic importance to improve the physical capacity of older people so that they can continue to work instead of either dying or retiring, with the loss of their productivity.

I see no other practical solutions to the problems of illegal immigration or the ecoonomic time bombs of deficits and entitlements.

Posted by: Doug Collins at November 16, 2008 9:47 AM

I agree with Reason. 100 years ago, life expectancy was just about half of what it is today. The world was much poorer.

Also, a longer professional life will enable more people to save for retirement, and will also give people more years to benefit from compounding annual returns. Their lives will overlap more with those of their grandchildren and great-granchildren.

"tilting society toward the old, infertile, and undynamic, and away from the opposite? "

This is also known as Europe and Japan. Even here, longer lives will offset low birthrates.

Posted by: GK at November 16, 2008 10:16 AM

With regard to the comment "The Mission Impossible of Genetic Redesign For Longevity" posted November 14:

"If you had to pick the absolute hardest, most challenging goal possible in biomedical science, I think it might be to alter the genes of adult humans so as to safely extend healthy life. Yet this is pretty much the course of the mainstream aging research community - and so I believe they are setting themselves up for maximal expense and minimal progress:"

I think few if any longevity researchers are out to alter the human genes with which we are born. They are out to alter the patterns of GENE EXPRESSION so as to enhance longevity. The patterns of gene expression in the body are always naturally in a dance of change and very many substances are known to be able to create such change, so why view the task as so difficult?

"Whether genetic redesigning can be achieved in the wake of numerous and complex epigenetic factors that effectively determine the life course and the life span of an individual still appears to be a 'mission impossible'."

Yes to the complexity of epigenetic factors and the multiple feedback loops involved. But each time we drink a cup of tea, discover a new drug, or confirm the longivity effect of a substance we are affecting the epigenetic pattern. Again, why mission impossible?

"Not impossible, just far, far harder than the alternative - which is to avoid changing human genes and metabolism, rather aiming to repair the damage of aging in the biochemistry we have today, thus reversing the effects of aging. That goal allows us to skip over a great many things we don't understand about human biochemistry and avoid many challenging endeavors - and it will produce more valuable and effective therapies into the bargain."

Here is where I believe the author is confused. "repair the damage of aging in the biochemistry we have" cannot take place with pliers and screwdrivers or involve swapping entire organs. It must involve molecular modifications of "the biochemistry we have" via epigenetic and metabolic changes. There is no other way. "repairing the damage of aging" means "make younger again" and our only and best hope is molecular biology and induced changes in epigenetic expression.

Posted by: Vince Giuliano at November 16, 2008 1:39 PM

Giuliano: replacing damaged mitochondrial DNA via protofection involves no directed epigenetic or metabolic changes, yet reverses that part of the damage of aging.

Infusing tissue with bacterial enzymes to digest unwanted extracellular aggregates involves no directed epigenetic or metabolic changes, yet reverses the accumulation of such aggregates and removes their contribution to aging.

And so forth.

Undirected epigenetic changes happen all the time - but that's a part of the normal operation of metabolism. Directed changes and their side-effects are the issue.

Posted by: Reason at November 16, 2008 2:22 PM

Reason is completely correct - solve the simpler immediate problems first - worry about the more complex and difficult to find cause second. See discussion at TED conference - http://www.ted.com/index.php/themes/might_you_live_a_great_deal_longer.html

MORE IMPORTANTLY, please consider that whether you believe that Reason is right or wrong in the shortest approach to increasing healthspan, that EITHER way, most of us who are ~40 or so are unlikely to see ++ increase lifespan - per projections done at SENS 3. (http://richardjschueler.com/gallery2/main.php?g2_itemId=56893)

This is unacceptable.

There is a temporising solution however if we invest our money wisely.

Right now '21st Century Medicine' - a US based transplant research company (who I am not involved with in any way) can reversibly suspend individual organs at -135C/-225F -where they can be stored theoretically for 10+ years. These organs can be returned and they function in live animals after suspension!
YOU are a bunch of organs... therefore it is just a matter of time... Reversible suspension or Ultrahibernation - call it what you wish, is around the corner. Suggest it needs a 'prize' :-)

We need it as insurance to 'jump forward' when we get a disease which is not 'yet' curable.

Regards
Dr AdrianT - PauseMe.Org

Posted by: Dr AdrianT at November 16, 2008 4:42 PM

the author continually states this point, that genetic manipulation is hard and inefficient, and repair is easy relatively speaking.

there's been some data in the past year refuting this. Gene expression has been alterered in low level organisms reducing the effects of aging, extending life. the very fact that "this has been done" makes it infinitely easier than the theory of SENS, which has not been done.

Low hanging fruit is low hanging fruit. When it is as clear to the scientific community that the repair associated with SENS is as easy or easier than what can be done via gene expression, they'll bite. Right now, they don't agree.

Posted by: int16 at November 17, 2008 9:33 AM

"Isn't such extension of life essentially robbing resources from the younger generations.."

By what right does this forgotten future seek to deny us our birthright? None I say! Let us take what is ours, chew and eat our fill.

Posted by: Jonathan at November 17, 2008 12:55 PM
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