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The Gerontology Journal Crusades


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#1

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Posted 28 June 2004 - 12:47 AM


Check out the TOC at the Journal of Gerontology for issue 59A number 6. Link (this is a link to the current TOC, if you are reading this after June make sure you are looking at the issue number provided)

There's a very interesting debate going on.

My institutional subscription only allows me full access to articles that are 2 months old, so I can only access the abstracts. Check out Hayflick's position:

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 59:B573-B578 (2004)
© 2004 The Gerontological Society of America

Aging: The Reality

"Anti-Aging" Is an Oxymoron
Leonard Hayflick

Department of Anatomy, University of California, San Francisco, School of Medicine.

Correspondence: Address correspondence to Leonard Hayflick, PhD, Professor of Anatomy, Department of Anatomy, University of California, San Francisco, School of Medicine, P.O. Box 89, The Sea Ranch, CA 95497. E-mail: len@gene.com

No intervention will slow, stop, or reverse the aging process in humans. Whether anti-aging medicine is, or is not, a legitimate science is completely dependent upon the definition of key terms that define the finitude of life: longevity determination, aging, and age-associated diseases. Only intervention in the latter by humans has been shown to affect life expectancy. When it becomes possible to slow, stop, or reverse the aging process in the simpler molecules that compose inanimate objects, such as machines, then that prospect may become tenable for the complex molecules that compose life forms. Most of the resources available under the rubric "aging research" are not used for that purpose at all, thus making the likelihood of intervention in the process even more remote. If age changes are the greatest risk factor for age-associated diseases (an almost universal belief), then why is the study of aging virtually neglected?


This is an outrageous stance. If anyone has access to the full article please post it.

Edited by prometheus, 28 June 2004 - 04:07 PM.


#2 ocsrazor

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Posted 28 June 2004 - 07:03 PM

Hayflick never did anything interesting in his career after discovering the Hayflick limit in graduate school. He is not known to be the sharpest of scientists and often makes inane comments such as those in that abstract. It is amazing to me he continues to get this stuff published with no data to back his commentary up.

The June issue isn't in the online database yet, remind me in a few days and I'll put it up.

#3

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Posted 29 June 2004 - 04:33 AM

When I see senior scientists with substantial research track records making anti anti-aging research comments like this it makes me wonder why. Did Dr. Hayflick's discovery of the cell division limit in somatic cells influence his course of thinking? Bear in mind that prior to his discovery it was thought that all cell could divide for ever. Or perhaps he is so annoyed at all the snake oil peddlers capitalizing on human weakness that he feels compelled to make very black and white stand.

In any case, I have tried to reconcile his distinguished record against his proclamations and considered that he may be in disagreement with the present state of affairs insofar as where research is heading rather than being utterly convinced that it is impossible to ever extend human life span by genetic interventions (which any scientist would completely disagree with, as given enough time and resources it is inevitable). In saying that no intervention will slow, stop, or reverse the aging process in humans, I suspect that he could be attacking the strategy of researchers in the field. Further in the abstract he says, most of the resources available under the rubric "aging research" are not used for that purpose at all, thus making the likelihood of intervention in the process even more remote, implying that he does not agree with the approach of investigators, and admitting that intervention is possible provided that resources are used for the right purpose.

The comment that is totally baseless, and in line with ocsrazor's "inane" descriptive is. when it becomes possible to slow, stop, or reverse the aging process in the simpler molecules that compose inanimate objects, such as machines, then that prospect may become tenable for the complex molecules that compose life forms. This is the sort of comment that finds safe harbor with amateur physicists and those we little or no biology background.

Man made machines, as per what we have made till today, do eventually break down. On the other hand, the genetic information that is carried in our cells has been in existence for millions of years, and so long as it has access to the energy yielded by the breaking of carbon bonds (or from the sun if you're a plant), will continue to do so indefinitely (provided you and your progenitors continue to transfer your germline). When you consider all of your ancestors that had sex, resulting in a sperm and egg being fused, sharing their plasma membrane and other cell components, and this event repeated for countless times through the ages, you can see a facet of immortality in defiance of entropy.

#4

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Posted 19 July 2004 - 10:19 AM

The June issue of Journals of Gerontology Series A: Biological Sciences and Medical Sciences finally came online today (about bloody time, as they say down under). After scanning all the articles here's a sampling:

1. Hayflick's ongoing pathological assertion that aging is caused only by molecular entropy and is a condition for which never will an intervention be found is counterbalanced by his observation that only microscopic amounts of resources are made available for research in this area. One at times feels that he is provoking the scientific community to get off their collective arse and prove him wrong.

I almost chocked on my omelet on this one and had to clean up my keyboard - it relates to Hayflick's molecular entropy theory and how genes are irrelevant to aging:

Just as a blueprint is vital to manufacture a complex machine and contains no information to cause the aging of that machine, the genome is necessary to govern biological development and maintenance but unnecessary to cause the animal's aging. The animal and the machine ultimately fail because of thermodynamically driven losses in molecular fidelity. In living systems, this continued loss of fidelity eventually exceeds repair capacity and leads to increased vulnerability to predation, accidents, or pathology. In inanimate objects, similar molecular changes also will exceed repair capacity and increase vulnerability to analogous irreversible failure in some vital component.

Because genes do not drive the aging process, an understanding of the human genome, even beyond what is known today, will not provide insights into a process that is random and thermodynamically driven.


But wait, there's more:

The belief, even among some gerontologists, that we are on the verge of intervening in the aging process in humans has become so widespread recently that several calls have been made to debate the value of doing so. They admonish us to engage in dialogues on the serious impact that having the ability to perturb the aging process in humans would bring to virtually all of our institutions.

Funnily enough there are a few of these "why should we live longer" types of articles in this issue. Of course he summarily trashes them. But does the usual bit of a "teaze" with how little research is being conducted.

It is doubtful that a public dialogue on this issue will ever be needed for several reasons, the least of which is that very little research is conducted on efforts to understand the biology of aging and even less is directed toward intervening in the process. Second, we cannot even slow, stop, or reverse the aging process in such far simpler entities than ourselves as are, for example, our own automobiles. Some have argued that this analogy is flawed because inanimate objects do not have the capability for repair, as do humans. However, our repair processes also age, and despite the existence of an enormous automobile repair industry, no one has yet solved the aging problem in cars or in the repair shops themselves, who like all else in the universe, suffer the same fate. As stated earlier, because the aging process is a universal property of all molecules (and most atoms), intervention in the aging process borders on the likelihood of violating fundamental laws of physics.


2. Holliday, with whom Hayflick debates also is convinced that an intervention for aging is virtually impossible despite the fact that he breaks down the cause of aging into numerous categories (the solution to some of these is where Aubrey de Grey's SENS is derived from). Like Hayflick, Holliday also agrees on the miniscule resources devoted to investigating the causes of aging.

Thankfully Holliday acknowledges the genetic contribution to aging:

The true number of genes involved in the determination of longevity is likely to be very large. Each maintenance mechanism depends on a large number of genes, for example, DNA repair has multiple pathways and each pathway depends on several enzymes. It is also now known that there are close interrelationships between DNA repair and the cell cycle. It would be damaging for a cell with unrepaired DNA lesions to attempt to divide, so such division only occurs when DNA repair is complete, apart from the special case of error-prone repair. There are many genes involved in other maintenance mechanisms, such as proteolysis, defense against ROS, the immune system, detoxification, and so forth. The conclusion must be that a very large number of genes control or determine, in one way or another, the efficiency of cell and tissue maintenance. All these genes contribute, to a greater or lesser extent, to the maximum longevity of the organism in a favorable environment. The very existence of multiple maintenance mechanisms also means that they act as different defenses against the multiple causes of aging.

3. The war on the fraudulent nature of the anti-aging industry is covered, which is something that is very important. There's a lot of misinformation out there by quasi-scientist or unethical scientist types who seek to validate the latest supplement or treatment by citing what appears to be relevant legitimate research. Of course the majority of people will have trouble getting past the heading from a pubmed article let alone be in the position to evaluate its relevance to the product advertised. It is becoming a lucrative industry:

A research report prepared by a "knowledge services company," FIND/SVP, estimates that the anti-aging market was about $43 billion in 2002 and could increase to $64 billion by 2007. However, it defines the market very broadly in terms of five categories: cosmetic treatments and surgery; exercise and therapy; food and beverages; vitamins, minerals, and supplements; and cosmetics and cosmeceuticals.

In my view none of the above categories constitute scientific and legitimate anti-aging which can only be brought about by changes in gene function. In this regard, I can sympathize with the vitriolic approach of some senior researchers towards the "anti-aging" movement.

I found this reference to Hayflick intriguing:

Even biogerontologist Leonard Hayflick-regarded by many in the field as having laid the groundwork for contemporary research advances in molecular mechanisms of aging - has long feared the societal implications of slowing or arresting the aging process such as worldwide overpopulation and its consequences. However, he joins with most other biogerontologists and gerontologists in regarding as highly desirable the compression of morbidity as long as it does not involve extending average life expectancy beyond 100 years.

Why are all these biogerontologists so scared of getting people to live longer if they think its so impossible?

#5 Bruce Klein

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Posted 19 July 2004 - 02:17 PM

Thanks Harold.

I think Hayflick has found a cause for which there is a receptive ear. He is playing the crowd.. but lives are being lost because of it.

#6 olaf.larsson

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Posted 20 July 2004 - 12:13 AM

People who are talking about living 500 years are considered to be unserious.
Like those in the 1920-ties that talked about going to the moon.

#7

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Posted 20 July 2004 - 04:14 AM

It is very difficult for even for me to envision a 500 year lifespan based on our present understanding. Reviewing all that is presently published between the field of the mechanisms of aging and the technology available to modify those mechanisms we find two challenges:

1. selecting which are the most pivotal genes whose regulation we need to modify
2. selecting the method by which modification can be effected.

My view, as many of you may already know, is that maintaining DNA integrity both in the nucleus and in mitochondria will result in a fundamental difference in the rate of aging. The number of studies that show that DNA damage is the trigger point for the pathway to altered cell function are too numerous to be ignored. Other factors, of course, will still prevail and contribute to the aging process but I am convinced that this is the fastest way to get a treatment out there that will make a real difference to human lifespan.

The hurdle of delivering these enhancements to as many cells in the body as possible remains unsolved. Thus we are limited as to the strategy of introducing these cellular changes. We know that we can target specific tissues such as the heart and the brain but we don't know how much of the overall organ will be able to benefit. Also, once more we are constrained by delivery since once we get the enhanced genes in the cell we cannot sustain their expression indefinitely. This would mean continued therapy until a more stable long term means of expression is discovered.

This is why these estimates of 500 years and such are so troubling to even the most optimistic of investigators - even the most determined optimist is tempered once aware of the scientific reality let alone those on the "no intervention is possible" crusade.

In my opinion, the very best that we can do right now is to start with efficacy studies on enhancing DNA integrity mechanisms starting with cost effective and rapid result studies in models such as drosophila (flies) and having proven that aging rate is retarded move up to mammalian models like mice using somatic gene intervention models to test for efficacy and safety.

Even if these studies were to commence today, we would still be looking 10 years from now before we could get data from mammalian models. Add another 5 years for government approval for human use. Suppose we are successful and show, say a doubling of lifespan and a substantial reduction in age related pathology, then we have the final problem and that is can we reverse aging in a cell that is already down the path? Do we want to reawaken a cell whose DNA is already damaged? Thus will this treatment be useful only to people under a certain age? Are the baby boomers are doomed?

There are so many of these questions that need to be answered by lab work. There are very few labs willing to run such experiments either for lack of funding or because the investigators are concerned about seen to be researching something as controversial as anti-aging.

Hayflick may be acting as a provocateur but on the whole he is simply discrediting the basis by which researchers can even entertain the notion of entering this field.

#8 olaf.larsson

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Posted 22 July 2004 - 06:50 PM

Yes so dont call your research "antiaging". Say that you are working on medicines against inherited mitochodria malfunction or medicines against malfunctional dna-copy mechanisms. And everyone will be happy and you will be considered a good scientist and not a loonatic.

#9

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Posted 23 July 2004 - 04:25 AM

Right on Wolfram. The strange thing is that were you were to do a search on pubmed for all the investigations that are associated with anti-aging but instead are described by the more esoteric scientific terms thousands of results would be returned. The scientific community fear to discredit their work by labeling it "anti-aging" but that results in a perception by those who don't know how to strategically "mine" for information that not much research is being done.

#10 Karomesis

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Posted 09 January 2005 - 01:19 AM

I do feel that this correspondence will take a drastic turn once negligible senesence is achieved in mice. those once deemed off the beaten scientific path will become revered for the brilliant individuals that they are for bringing the salvation of the fountain of youth to the uninformed and oftentimes foolhardy masses. I believe that the message being prosletysed herein is fundamentally difficult for the vast majority of humanity to grasp. I also do not think that this will change once mice live for the human eqivalent of 500 years in good health and youth. the masses will still proclaim that mice are not humans and until such longevity occurs in homo sapiens sapiens then the conversation is therefore concluded. [ang]

#11 bodebliss

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Posted 26 February 2005 - 07:01 AM

Well Hayflick reminds us that scientist are least likely to know the implications of the current research. It takes men of vision for that. The inventor of the computer said he saw a need for maybe 5 such devices. IBM didn't think anyone else would need an operating system that's why they gave right to Bill Gates to lease to them and others. It's the same reason why Apple didn't retain all rights to windows. Crick and Watson had no idea where the discovery of DNA would lead. The forward leading edge of the battle zone or discovery zone shifts and bulges, ebbs and flows over here for a while, over there a bit, then it dries up and surges in another place only faster and more far reaching for awhile. Ya gotta keep your eyes open.




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