The Engineer's Viewpoint: Treat Change as Damage and Fix It
Permalink | View Comments (12) | Post Comment | | Posted by Reason

An aging body has changed in many ways, and not just in those obvious to visual inspection. The typical old body is identifiably different from the typical middle-aged body at the level of cells, genes and biochemistry: biochemical processes, gene expression, levels of molecular damage, cellular behaviors, cellular populations, and so on.

Some of these differences are clearly causally linked - a wide range of age-related changes can often be shown to be caused by a lesser number of underlying changes. For example, damage to mitochondria leads to oxidization of low-density lipoproteins (LDL), which in turn leads to detrimental changes involved in atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease. Most modes of biochemical wear and tear contribute to a wide range of recognized age-related conditions and frailty.

One role of aging research should be to explore these linkages, so as to better characterize the core of aging; what, really, are the essential changes of aging when all the chains of failure have been cut back to their root causes?

The other role of aging research - a role that continues to be woefully underserved - is to develop the means to prevent and repair changes associated with aging. This is where the engineering and scientific viewpoints tend to diverge. Scientific culture aims for full understanding prior to action; engineering culture aims for enough information to enable working, reliable tools and outcomes. Strong, long-lasting bridges and large buildings existed long before the tools and knowledge to completely understand strategies for architecture and construction. Similarly, an engineering approach to aging could make meaningful inroads in extending our healthy life span prior to a complete scientific understanding of all the complex change that comes with the passing of years and the workings of our bodies.

At root, what the engineer proposes is to fix all observed change. Science is essential to this goal - it reduces the problem space down to one that can be tackled in a short enough timeframe by identifying root causes. Science then provides the knowledge needed to build the tools - modern biotechnology in this case - to do the job. But you have to recognize the point at which there is enough information to set forth and engineer results; this point is usually far in advance of complete understanding.

Don't know whether a characteristic change between an aged body and a youthful body is harmful? Work to fix it anyway. The worst that can happen at the end of the day is you'll make an aged body even more like the youthful body next door, but gain little in the doing of it.

As it turns out, the list of root causes (changes that occur with aging) looks to be small, especially when considering the fact that gerontologists have divided the world of the failing human body into thousands of named medical conditions. I'm sure most of you are familar with the list from the Strategies for Engineered Negligible Senescence, an engineering-oriented proposal and young research program to extend the healthy human life span by reversing changes that occur with aging:

Some tissues lose cells with advancing age, like the heart and areas of the brain. Stem cell research and regenerative medicine are already providing very promising answers to degeneration through cell loss.

We must eliminate the telomere-related mechanisms that lead to cancer. de Grey suggests selectively modifying our telomere elongation genes by tissue type using targeted gene therapies.

Mitochondrial DNA is outside the cellular nucleus and accumulates damage with age that impairs its critical functions. de Grey suggests using gene therapy to copy mitochondrial DNA into the cellular nucleus. Other strategies for manipulating and repairing damaged mitochondrial DNA in situ were demonstrated for the first time in 2005.

Some of the proteins outside our cells, such as those vital to artery walls and skin elasticity, are created early in our life and never recycled or recycled very slowly. These long-lived proteins are susceptible to chemical reactions that degrade their effectiveness. Scientists can search for suitable enzymes or compounds to break down problem proteins that the body cannot handle.

Certain classes of senescent cell accumulate where they are not wanted, such as in the joints. We could in principle use immune therapies to tailor our immune systems to destroy cells as they become senescent and thus prevent any related problems.

As we age, junk material known as amyloid accumulates outside cells. Immune therapies (vaccines) are currently under development for Alzheimer's, a condition featuring prominent amyloid plaques, and similar efforts could be applied to other classes of extracellular junk material.

Junk material builds up within non-dividing, long-life span cells, impairing functions and causing damage. The biochemistry of this junk is fairly well understood; the problem lies in developing a therapy to break down the unwanted material. de Grey suggests searching for suitable non-toxic microbial enzymes in soil bacteria that could be safely introduced into human cells.

You'll find one of these classes of change mentioned today at Ouroboros:

I currently work on a phenomenon known as cellular senescence, which is a permanent growth arrest caused by telomere dysfunction (e.g., the critically shortened telomeres that arise after many cell divisions) and also by other kinds of stress (particularly genotoxic damage).

One of the active controversies in this sub-field of biogerontology is, somewhat paradoxically, whether it’s part of biogerontology at all: While senescence certainly arises as cells get older in culture, and while there’s a good story to be told about how senescent cells could contribute to age related decline in tissue function, it’s not yet fully clear to what extent the phenomenon actually plays a role in physiological aging of intact animals.

Research scientists will keep investigating. In the meanwhile, given that the buildup of senescent cells accounts for a significant fraction of some tissues in later life, the engineers should already be looking at potential fixes. It's not hard to think of approaches to reversing the acculumation of senescent cells in this day and age of targeted therapies for discriminating cell destruction and other advanced biotechnology under development:

Getting rid of cells is a much simpler job than most of the other things we have to do as part of SENS. In the case of fat, it's possible to use simple surgery, but that's unnecessarily invasive. There are two main other ways: we can inject something that makes the unwanted cells commit suicide but doesn't touch other cells, or we can stimulate the immune system to kill the target cells. Both approaches involve making use of distinctive molecules on the surface of the target cells: luckily, different cell types tend to have different things on their surface, so this shouldn't be too hard. But it hasn't been done yet, and not enough people are working on it -- it needs much more attention.

Sadly, comparatively little funding is directed towards any of this, and the engineering side garners far less than the better established investigative community. That will have to change, and the way it changes is the same way it changed for other growth fields in science: the bootstrapping of advocacy and progress side by side, within and without the scientific community.

Technorati tags: , ,

Comments

Much of the evidence points to oxidative damage as the main cause of aging. Dna copying errors are a very creative force in the evolutionary process,but highly destructive for the individual organism. I am starting to think we would need nanotechnology to repair the Dna damage,and therefore reverse the aging process.

Posted by: Tj Green at January 14, 2007 12:17 PM

HUMAN CLONING IS THE ULTIMATE ANSWER FOR LONGEVITY,TILL WE KNOW THE ROOT CAUSE OF AGING PROCESS AND FIND THE TECHNOLOGY FOR ITS CORRECTION.IF WE ARE ABLE TO DIRECT THE STEM CELLS TOWARDS ORGAN CULTURE OR TISSUE CULTURE WE CAN GET HLA COMPATIBLE SPARES OF BODY.IN THIS WAY WE CAN INCREASE HUMAN LIFE SPAN UPTO 500 YEARS OR MORE.

Posted by: DR.S.R.DESAI at February 22, 2007 4:30 AM

When clones are born, they are people, not organ farms.

Posted by: David at October 11, 2007 12:12 PM

What would happen with the social structures and balance in the society if we have 300 years old humans with the body and biochemistry of 20 years old? Young people are credited with emotional and revolutionary thinking partially because of their body chemistry whereas the older people are considered generally to be more settled and wise.... Maybe aging is necessary for the evolution of the species and societies?! Would you like to be enslaved and have a dictator for a master that would live forever?
Nevertheless as a selfish being I would like clearly to state that "I want to live forever!"… given that I am free to make my own choices.

Posted by: George Spilkov at December 30, 2007 12:29 AM

To those who doubt that we can develop ways to extend our health and longevity, I offer the following true historical perspectives on what is and is not possible:
FAMOUS LAST WORDS:
***"Man will never reach the moon regardless of all future scientific advances." Dr. Lee DeForest, Father of Radio & Grandfather of Television.
***"I think there is a world market for maybe five computers." Thomas Watson, chairman of IBM, 1943 (good he didn't stay)
***"640K ought to be enough for anybody." Bill Gates, 1981
***"There is no likelihood man can ever tap the power of the atom." Robert Millikan, Nobel Prize in Physics, 1923
***"Computers in the future may weigh no more than 1.5 tons." Popular Mechanics, 1949
***"I think there is a world market for maybe five computers." Thomas Watson, chairman of IBM, 1943 (good he didn't stay)
***"The bomb will never go off. I speak as an expert in explosives." Admiral William Leahy, US Atomic Bomb Project
***"We don't like their sound, and guitar music is on the way out," Decca Recording Co. rejecting the Beatles, 1962.
***“This 'telephone' has too many shortcomings to be seriously considered as a means of communication. The device is inherently of no value to us," – Western Union, 1876.
***"Heavier-than-air flying machines are impossible," -- Lord Kelvin, 1895.
***"Drill for oil? You mean drill into the ground to try and find oil? You're crazy," When Edwin L. Drake tried to enlist funds for his project to drill for oil in 1859.
***"The abdomen, the chest, and the brain will forever be shut from the intrusion of the wise and humane surgeon," -- Sir John Eric Ericksen, British surgeon to Queen Victoria.
***"Louis Pasteur's theory of germs is ridiculous fiction." Pierre Pachet, Professor of Physiology at Toulouse, 1872

Posted by: Carl Bourhenne at January 28, 2008 1:01 PM

Carl: of course we can develop extend our healthspan, the question is when will this be significant?

Tj Green: oxidative damage is a factor in ageing but there are plenty of others and i see no evidence that it is the main cause. What has this to do with errors in DNA replication? Note that most errors are corrected and when they're not you get cancer, not ageing.

Posted by: richard at September 22, 2010 9:23 AM

I wonder if it would be possible to stimulate/genetically alter our bone marrow to constantly produce stem cells and then have these stem cells transported round the body via the circulatory system. If so, then maybe old, damaged cells would be constantly replaced by fresh, new cells, completely free of damage or mutation.

Posted by: Sam at June 14, 2011 8:15 AM

Perhaps the whole issue can be reduced to examine the subject of cell reproduction and make from a right time, the replica is exact, perfect, ie without the loss or mutation of any cellular element, so that from then on later, nothing changes in the body genetically.

Posted by: edu at October 19, 2012 7:01 AM

As Carl Bourhenne mentions above, anything is possible.

Posted by: Brandon at January 19, 2013 10:22 PM

i would like to live forever and believe we are nearing to solving this matter than people would think if only we could continualy give the body all the vitamins it need,s i do not believe the body would age but ourt mind must be balanced and prepared at first i believe yoga would help calm the mind and your belief would need to be strong

Posted by: gerald jagla at April 27, 2013 8:12 AM

Realmente hay un montón de fondos publicos y privados que son tirados a la basura cada día. Tenemos toda la industria cosmetica de cremas por ejemplo moviendo unos 250.000 millones de dolares anuales, sin tener ningún resultado real. Tenemos cantidades de gentes con ingresos que van a parar en la bebida y desbordes personales. Realmente, los politicos que dirigen las naciones, aún no están a la altura necesaria con los cambios que han habido en la ciencia y la tecnología, en los últimos 15 años. Habrá que esperar unas cuantas décadas más para que se pongan a tono con esto y aprendan a redirigir, esos excesos de fondos hacia fines útiles...el resto, al menos hasta hoy, es sólo utopía...lamentablemente.

Posted by: eduardo at January 24, 2014 10:14 AM

There is a lot of public and private funds that are thrown away every day. We have all the cosmetic creams industry for example moving some 250,000 million dollars annually, without having any real results. We have numbers of people with incomes that end up in the drink and personal excesses. Actually, the politicians who govern our nations, are not yet at the required height with the changes that have occurred in science and technology over the past 15 years. Let's wait a few more decades to put in tune with this and learn to redirect, those excess funds to other useful purposes ... at least until now, is just utopia ... unfortunately.

Posted by: eduardo at January 24, 2014 10:17 AM
Post a comment; thoughtful, considered opinions are valued. Please note that comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.









Remember personal info?