My first publication!

My first publication is in print, titled "Thermodynamics and Information in Aging: Why Aging Is Not a Mystery and How We Will Be Able to Make Rational Interventions"

Its available at the Rejuvenation Research website:
http://www.lieberton...-d7nk_aOd?part=

Ironically, I can't afford a personal subscription and don't have access to my own paper at the moment! If somebody else with a subscription could post the paper in this thread it would be appreciated.

Comments please!

Great job!

Look forward to reading it soon.

*smashes a bottle of french champaign*
Congrats!
Here ya go [tung]

Congratulations Mark!

In 2005 Hamalainen proposed that having an artificial reference for genetic information is a means by which genomic stability could be maintained (1).


(1) REJUVENATION RESEARCH Volume 8, Number 1, 2005
Thermodynamics and Information in Aging: Why Aging Is Not a Mystery and How We Will Be Able to Make Rational Interventions
MARK HAMALAINEN

Yes, congratulations!

I'm seriously impressed.

I'll print this one out and read it on the train tonight. [thumb]

Write also for men in the street.


Allow me to join the chorus of Hallmark Greeting Card posters here so far.

Congratulations!


From the title of your post, "Thermodynamics and Information in Aging: Why Aging Is Not a Mystery and How We Will Be Able to Make Rational Interventions", and from the publication outlet where it is put on sale, to all appearances your text is an exposition and advocacy piece of writing addressed to people already in the know, in technical language, and for people who will pay to read it.

Please also write on the same materials for men in the street, and for free. That should be the real challenge and will make you even more insightful of your subject of mastery, and make you a hero for men in the street of which the number is infinite.


The title of your thread is "My first publication!, comments please", and you end your OP with the entreaty, Comments please! The above words are my comments.


Susma

My first publication!, comments please 

My first publication is in print, titled "Thermodynamics and Information in Aging: Why Aging Is Not a Mystery and How We Will Be Able to Make Rational Interventions"

Its available at the Rejuvenation Research website:
http://www.lieberton...-d7nk_aOd?part=

Ironically, I can't afford a personal subscription and don't have access to my own paper at the moment!  If somebody else with a subscription could post the paper in this thread it would be appreciated.

Comments please!

Allow me to join the chorus of Hallmark Greeting Card posters here so far.

hehe, yeah, but thanks guys! we can share that bottle of champaign in september at SENS2!

to all appearances your text is an exposition and advocacy piece of writing addressed to people already in the know, in technical language, and for people who will pay to read it.

Did you read it? I didn't think it was very technical. If I was to explain the background enough such that non-science educated people could understand every detail, I'd have to write a small book, thats why I referred to Aubrey de Grey's excellent primer.

Please also write on the same materials for men in the street, and for free. That should be the real challenge and will make you even more insightful of your subject of mastery, and make you a hero for men in the street of which the number is infinite.

Anybody could distribute a non-technical paper for free which claimed aging wasn't a mystery, but would they be taken seriously, especially given the awful but popular magazines like scientific american which continue to repeat the same messages year after year about calorie restriction and how we should be humble in the face of nature's complexity, which is beyond our current understanding (Even the recent aging feature in Cell was quite disappointing and unoriginal)? I hope to be in a position some day soon to be taken seriously, once I have some research under my belt. But for now, de Grey is doing excellent work on the publicity front. The purpose of my paper was to present what I think is an original idea, or different way of looking at things. What did you think of my ideas?

Still trying to finish it. My 3 yr old does not like having my attention on anything but her.

Write also for men in the street.

From the title of your post, "Thermodynamics and Information in Aging: Why Aging Is Not a Mystery and How We Will Be Able to Make Rational Interventions", and from the publication outlet where it is put on sale, to all appearances your text is an exposition and advocacy piece of writing addressed to people already in the know, in technical language, and for people who will pay to read it.

Please also write on the same materials for men in the street, and for free.
Susma

Why not do it yourself?

Oh sure, it would mean you'd have to learn how to construct an English sentence that looks just a little more natural, but I think people would be glad to read about your strong opinions on all sorts of stuff.

Try me.

Dear Osiris:

A real scholar, I salute you; otherwise you would have gotten all huff and puff from my post.

No, I haven't read your text. But continue in your work, and let not the less palatable comments of Susma deter you from further endeavors. You are in the right direction.

If and when you do write about your idea that newspapers, even just and specially the hometown one, will publish, I would appreciate a notice of where I can read it for free.

Best regards.

Susma

Let others do what you can't do yourself or for yourself.

Dear Jay:

I read somewhere that mothers there are who feed their babies by chewing food in their mouths and then serving it on a spoon back to their babies.

I am dedicated to the proposition that what others can do for me, I will invite them to do so, specially when they derive pleasure from the act of service.

On the other hand, I am not conversant with a lot of technical matters from Osiris, and also with analogous similar matters from others here, that Osiris and others here in this forum are well-versed in. Sometimes I even ask hat in hands the experts here to explain things to me, like John Sho who is a very good teacher in this regard.

About my sentence structure, we all do have to develop our affectations, don't we? If my sentences are peculiar, they do I hope strike an effect.

Best regards,

Susma

Why not do it yourself?

Oh sure, it would mean you'd have to learn how to construct an English sentence that looks just a little more natural, but I think people would be glad to read about your strong opinions on all sorts of stuff.

Okay, here are some comments & questions...
I tend to be a bit timid in my thinking, and your paper certainly presents some bold ideas. So please don't be offended by my nit-picking. Also, it has been a long, long time since I've been in school; I've forgotten a lot and a lot has changed.

Some gerontologists hold that aging is primarily a programmed phenomenon; however, the programs they suggest generally act by affecting the rate of aging..., not aging itself. They would be better referred to as longevity programs.

That's probably the 'camp' to which I belong. Another reason you might not want to bother with my comments.

This process works most efficiently when single copies of genetic information are passed between generations. Each extra copy would increase the probability of the new organism carrying a deleterious mutation, decreasing the fractional size of the viable subset.

I'm not sure I understand this. Are you saying that diploidy/polyploidy is disadvantageous? There is the 'repair hypothesis':
http://www.ncbi.nlm....st_uids=3324702

The goal would then be replacement of as much somatic tissue as possible, followed by chemotherapy to destroy the remaining original cells.

Will this 'work' with brain tissue?


~~~

Again, congratulations on your work. A new scholarly publication *is* a big deal.

I tend to be a bit timid in my thinking, and your paper certainly presents some bold ideas. So please don't be offended by my nit-picking. Also, it has been a long, long time since I've been in school; I've forgotten a lot and a lot has changed.

I'm glad for your comments, explaining my ideas to someone else is one of the best ways I can improve my own understanding.

This process works most efficiently when single copies of genetic information are passed between generations. Each extra copy would increase the probability of the new organism carrying a deleterious mutation, decreasing the fractional size of the viable subset.

I'm not sure I understand this. Are you saying that diploidy/polyploidy is disadvantageous? There is the 'repair hypothesis'

Diploidy/polyploidy can be extremely advantageous when properly put to use. The single copy state is only advantageous for the moment where genetic information is passed from one generation to the next (haploid gametes). Selection can then act upon the entire copy if information, even if it is duplicated immediately afterwards for purposes of error correction. In other words, all of the DNA of the organism is copied from one set of genetic information, so defects cannot hide behind other copies as would be possible in a chimera.

The goal would then be replacement of as much somatic tissue as possible, followed by chemotherapy to destroy the remaining original cells.

Will this 'work' with brain tissue?

I stated in my paper that, with the exception of cancer, primary aging is not fatal within normal human lifespan. Secondary and tertiary aging can be treated in the brain without large scale tissue replacement, and I expect this will be sufficient until more advanced measures are within our abilities. Also, turnover does occur in the brain, so some tissue replacement may be performed in sufficiently small doses.

So no, that strategy will not work in the brain, but there are things we can do to put off dealing with primary aging of the nervous system directly.

Allright, to business... This is an excellent model, representing the key features of aging with what I believe is unprecedented conceptual clarity. You have demonstrated that hypotheses on aging and anti-aging interventions can be formulated within this model efficiently and I have questions as for one such "implication":

[maintaining an ageless somatic body can be] achieved by creating a higher level artificial information reference.

stem cell therapy, [...] in its current form, will fail for the same reasons that the somatic body does.

Random mutations to a germ-line’s genetic information are constantly occurring [...] however [...] it is always possible to maintain a viable subset.

This suggests to use the germ line as the reference, by embryonic stem cell (ESC) therapy (which goes like fertilization - limited expansion - freezing - on demand thawing - massive expansion - differentiation - transplantation). During the brief culture periods required by this scheme, I do not see how any type of accumulating damage would have much of a chance to reach deleterious levels.
1) Do you think ESC, derived relatively fresh from the germline could provide the reference?

In order to create an ageless organism, every cell of the body must be augmented with (at least): genes for removing all MEPs, allotopically expressed mitochondrial genes, reprogrammed senescence and other active aging pathways, and a mechanism for inducing apoptosis or cell death to facilitate turnover of genetic information.

2) Are you literally referring to all cells of the body, including HTT (high turnover tissues) in the course of a therapeutic life-extension scheme that involves massive cell replacement?
3) If you think HTT may do without certain augmentations (e.g. allotopic expression), what do you think are the prospects of turning some of those tissues which are presently LTT into HTT (or at least into medium-TT), in the face of recent advances in ESC therapy of heart and brain?
4) Do you think some MEPs can be removed by means that are not genes, e.g. protein therapy for catabolism, guided ultrasound for cell ablation, ect. and do you think these possibilities can be more efficient?

engineer stem cells with specific resistances to and dependencies on certain chemicals

It is nice to see the similarity to my own proposal. Do you have some concrete systems in mind, especially as for "dependencies on certain chemicals?"

1) Do you think ESC, derived relatively fresh from the germline could provide the reference?

Yes, I think ESCs would be more than sufficient for the purposes of reaching escape velocity. However, more direct control will be required eventually, i.e. chromosome synthesis, and would obviously be advantageous for many other reasons.

2) Are you literally referring to all cells of the body, including HTT (high turnover tissues) in the course of a therapeutic life-extension scheme that involves massive cell replacement?

Since the HTT are being turned over quickly, secondary aging will not be a major problem in them. However, in the earlier stages of SENS use, stress on the body will undoubtedly be high, and any and all ways of reducing that stress by reducing the frequency of cell replacement or otherwise, will be desireable. Also, if we need to include a payload of genetic information for the chemotherapy dependencies, we might as well include as many other advantageous genes as we can.

3) If you think HTT may do without certain augmentations (e.g. allotopic expression), what do you think are the prospects of turning some of those tissues which are presently LTT into HTT (or at least into medium-TT), in the face of recent advances in ESC therapy of heart and brain?

LTT will have to be replaced at some rate, and the ideal rate may be that of 'mediam-TT'. I have a distaste for making us dependent on frequent tissue replacement beyond what its absolutely necessary. That may just be a personal bias, but there certainly are risks involved in frequent large scale tissue replacement.

4) Do you think some MEPs can be removed by means that are not genes, e.g. protein therapy for catabolism, guided ultrasound for cell ablation, ect. and do you think these possibilities can be more efficient?

MEPs could be treated by other means, and in the CNS they initially will have to be. As for which strategy is more efficient, that would depend on how the specific treatments are designed. I think protein therapy and other such technologies may be complementary to internal MEP removal, but generally couldn't be as efficient as having the cells clean themselves up. I see protein therapy as an approximation to internal MEP removal.

It is nice to see the similarity to my own proposal. Do you have some concrete systems in mind, especially as for "dependencies on certain chemicals?"

Unfortunately I don't have any specifics in mind, it was a purely theoretical exercise. I was impressed with your proposal, but I haven't commented on it since I don't know enough about the subject to say anything useful. I bought two books on stem cell biology and tissue therapy from the New York Academy of Science (Annals volume 961 and 944) and plan to read them after exams (they definitely don't teach this stuff in undergrad). Then hopefully I can be of some help, perhaps we'll collaberate in the future

That'd be awesome.

I love this statement:

In order for life to stabilize information in a
viable form it needs a method of entropy export.
This is provided by replication coupled
with natural selection.

Edited by rhaze, 26 April 2005 - 01:28 PM.

I haven't yet completely scrutinized your article but it seemed to me that you were saying something like that as a matter of principle, the body cannot detect and eliminate mutated somatic cells well enough. This would place an upper limit for the functional lifespan of the body. As the deterioration of the genome in somatic cells cannot be avoided, there is no point in having machinery for fixing, say, accumulating lipofuscin.

However, there are great differences in aging speed between different animal species, and it seems that the rate of aging depends a lot on how dangerous lives the animals lead. If one is a small, land-living creature, it is best to make as many offspring as early as possible, before one gets eaten by a predator. Fast reproduction probably means less resources for repairing accumulating damage, it might actually speed up the aging process. However, that doesn't matter, because one very likely gets eaten by someone else anyway.

Small birds age slower than small mammals, in general, even though their metabolic rates are faster. They start reproducing later and only at certain times of the year. Mice can do it more continuously and have litters that are of greater size, I think.

Some whales are said to live over 200 years old. It would make sense, as a full-grown whale has no natural enemies. Its best reproductive strategy would be to produce a steady flow of offspring, one at a time, over a long time, without sacrificing itself. Also, female tortoises take several years to start laying eggs, and they keep doing that for over 100 years, at least some species.

So what I'm saying is that the age that the maintenance systems try to reach "by defauls" probably depends more on ecological factors than the this thermodynamical issue.

So what I'm saying is that the age that the maintenance systems try to reach "by defauls" probably depends more on ecological factors than the this thermodynamical issue.

Both play a role. Ecological factors determine how much energy a species will invest to slow aging. However, the purpose of my paper was to explain how whatever the rate, aging is inevitible for life of our basic design.

However, the purpose of my paper was to explain how whatever the rate, aging is inevitible for life of our basic design.

That seems feasible to me, yes.

Foundational principles, such as the evolutionary origins and physiological definition of aging, remain controversial.

Do you have any references for controversy of the evolutionary origins? I have written an article once (it is hosted on ImmInst if you care to see it) about the evolutionary context of ageing, and I intend to re-write it for myself without a word limit (the previous paper was actually a university assignment). This time though, I intend on being much more thorough and covering many more aspects, and perhaps trying to build a current understanding picture of aging in context of the evolutionary theory that I propose. So far though, I havent seen much controversy over the evolutionary theopry of ageing..it all seems really straight forward to me. So I ask because there is a good chance I am allowing myself to be blinded by my pre-conceived beleifs.

Some gerontologists hold that aging is primarily a programmed phenomenon; however, the programs they suggest generally act by affecting the rate of aging (such as insulin, stress, and caloric restriction), not aging itself. They would be better referred to as longevity programs.

On a similar note, I always find the concept of any biologist thinking of ageing as a programmed phenomenon to be insulting. I agree with you re-phrasing of it, the body may have numerous longevity programs aimed to slow down the natural ageing process, but ageing itself as a predesigned program is against everything that evolution would be expected to design. This is one of the main reasons I want to do a more thorough discussion on evolutionary context of aging: until we know with a high degree of certainty how ageing came to be in the first place, we wont know for sure what is and isn't possible.

Sorry, I don't have any specific references as to the controversy. Part of what I see as the controversy is semantical, like the example of 'aging programs' being a misnomer. But aside from papers, in my experience of talking with and emailing various people who do aging related research, their ideas as to what aging is and how it could be treated tend to be very diverse and often quite obviously (to me at least) flawed. For example, I've had discussions with a number of people (from two different labs that study longevity) who are convinced that aging can be eliminated by finding the right combinations of mutations in certain genes.

until we know with a high degree of certainty how ageing came to be in the first place, we wont know for sure what is and isn't possible

But that is just what I answered with my paper. Aging is an inevitible result of information maintainence and copying being less than 100% efficient, and the details, or specific physiological causes of death and disease, are shaped by evolutionary pressures.

*smashes a bottle of french champaign*
Congrats!
Here ya go [tung]

Excellent read!

Thank you.

[thumb]