Science of Ageing

Discussions on topics related to biochemistry and molecular biology, functional genomics, etc.

Re: Science of Ageing

Postby SciameriKen on September 4th, 2015, 12:58 pm 

BioWizard » Fri Sep 04, 2015 2:59 pm wrote:Indeed so neuro. And the consensus that is finally becoming clear from all the ageing research (and noise) is similar to things we've been discussing here. It's a complex, actively regulated program that cannot be simplified into a single mechanism/regulator/hallmark/etc. It is clearly an interaction of a large number of genes and cellular processes, which combined set the dial on the "natural" lifespan of an organism.


This is what I was trying to say in the other thread - but very nice and succinct here :)

I however take exception as to whether it is an "actively regulated program", as program implies an intended process. Unfortunately, I still do not have time to go into it these days :)
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Re: Science of Ageing

Postby BioWizard on September 4th, 2015, 1:02 pm 

I was mostly paraphrasing neuron's comment that it's a gene regulated "program", much like homeostasis or apoptosis. I don't know if my use of the word "program" creates any unintended philosophical implications, but the point that it's gene-regulated appears to be true.
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Re: Science of Ageing

Postby neuro on September 4th, 2015, 1:32 pm 

I would like to apologize for the use of the word "program".
That comes from biological jargon.
We use the term "programmed death" to indicate apoptosis, which is a sequence of ordered cellular events ending up in cell fragmentation and engulfment and digestion of such fragments by macrophages, with no inflammatory response.

The word program is used here with no implication of intended design, in the lack of a better word to indicate an ordered and precisely controlled ("control" also seems to imply design and intention) series of events and processes that constantly ends up the same way...
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Re: Science of Ageing

Postby BioWizard on December 16th, 2016, 1:13 pm 

More on reprogramming the ageing process:

https://cdn.ampproject.org/c/nypost.com ... youth/amp/

p.s: beware of overhyped scientific reporting.
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Re: Science of Ageing

Postby vivian maxine on December 16th, 2016, 1:23 pm 

Ah well, that's in California. They live differently in California. I'm glad he ended with "we aren't mice".
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Re: Science of Ageing

Postby BioWizard on January 13th, 2017, 11:21 pm 

Another nail in the coffin of various thermodynamic decay/oxidative damage/telomere shortening/etc aging theories, and an additional clear proof that aging is a cellular program:

http://www.cell.com/fulltext/S0092-8674(16)31664-6

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

•Partial reprogramming erases cellular markers of aging in mouse and human cells
•Induction of OSKM in progeria mice ameliorates signs of aging and extends lifespan
•In vivo reprogramming improves regeneration in 12-month-old wild-type mice

Summary
Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.


Funny thing, one of the authors is an old colleague of SciKen's and I. Now we're two against one :]
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Re: Science of Ageing

Postby SciameriKen on January 14th, 2017, 10:03 pm 

BioWizard » Sat Jan 14, 2017 3:21 am wrote:Another nail in the coffins various thermodynamic decay/oxidative damage/telomere shortening/etc aging theories, and an additional clear proof that aging is a cellular program:

http://www.cell.com/fulltext/S0092-8674(16)31664-6

In Vivo Amelioration of Age-Associated Hallmarks by Partial Reprogramming

•Partial reprogramming erases cellular markers of aging in mouse and human cells
•Induction of OSKM in progeria mice ameliorates signs of aging and extends lifespan
•In vivo reprogramming improves regeneration in 12-month-old wild-type mice

Summary
Aging is the major risk factor for many human diseases. In vitro studies have demonstrated that cellular reprogramming to pluripotency reverses cellular age, but alteration of the aging process through reprogramming has not been directly demonstrated in vivo. Here, we report that partial reprogramming by short-term cyclic expression of Oct4, Sox2, Klf4, and c-Myc (OSKM) ameliorates cellular and physiological hallmarks of aging and prolongs lifespan in a mouse model of premature aging. Similarly, expression of OSKM in vivo improves recovery from metabolic disease and muscle injury in older wild-type mice. The amelioration of age-associated phenotypes by epigenetic remodeling during cellular reprogramming highlights the role of epigenetic dysregulation as a driver of mammalian aging. Establishing in vivo platforms to modulate age-associated epigenetic marks may provide further insights into the biology of aging.


Funny thing, one of the authors is an old colleague of SciKen's and I. Now we're two against one :]



I am looking at the white flag - but I haven't waved it just yet :D I haven't fully read through the paper after all :D This is certainly a landmark paper that highlights the commanding role of epigenetics on aging. Here is a recent review on this topic: http://www.sciencedirect.com/science/ar ... 741500007X. My first take on this is that so called "genetic drift" and the hyper/hypo-methylation of CpG islands is a time dependent mechanism that slowly increases susceptibility to the classic hallmarks of aging (Telomere shortening, DNA damage, mitochondrial decline, etc, etc) -which we would otherwise term wear and tear aging. The present study demonstrates reversal of many of these hallmarks through forced expression of otherwise heterochromatin silenced genes (Oct4, Sox2, Klf4, and c-Myc (OSKM)). Important points are that the induced expression is transient, where previous studies saw disastrous results when turning these genes on at all times. Still, these are only 4 genes, and if you could imagine what other genes are being silenced that we want, or turned on that we don't want, this could very well be the explanation of aging. This also may explain a important phenomenon Bio often asks about, which is if cellular aging is so prominent then why are germline cells spared? In this model, the germline cells clear and "reprogram" their epigenetic patterns, thus leading to renewal.

However, I would not know how this would explain why humans live 80 years and mice only 3 years unless there is evidence that epigenetic programming occurs faster in mice, and/or, perhaps Humans have a more sophisticated system to handle epigentics?

Fascinating stuff for sure!
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Re: Science of Ageing

Postby BioWizard on January 14th, 2017, 10:44 pm 

I'm not sure why we're specifically placing it in epigenetics now? Epigenetic modulation is just another mechanism of gene expression regulation. It's no more or less special than transcription, translation, posttanslational modification, and all the biochemical activities the various gene products carry out. I don't understand why people need it to be one thing. Oxidative stress, telomere length, epigenetic remodeling, etc etc. The point here is that lifespan is coded as a developmental program which derives from the genetic blueprint and all the molecular activities that both derive from it and give rise to it. If that wasn't the case, median lifespans of different species wouldn't be so different. Why is so easy to accept that embryological development follow a fixed timespan due to genetic programming, but so difficult to accept the same about adult development (i.e. lifespan)? Especially with so much evidence pointing to it being a genetic program, and so much more having been published since I started this thread back in 2009!
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Re: Science of Ageing

Postby Braininvat on January 14th, 2017, 11:54 pm 

Let's not rule out the anti-aging effects of beer, also. When I have several beers, my wife appears to be years younger.
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Re: Science of Ageing

Postby SciameriKen on January 15th, 2017, 12:45 am 

BioWizard » Sun Jan 15, 2017 2:44 am wrote:I'm not sure why we're specifically placing it in epigenetics now? Epigenetic modulation is just another mechanism of gene expression regulation. It's no more or less special than transcription, translation, posttanslational modification, and all the biochemical activities the various gene products carry out. I don't understand why people need it to be one thing. Oxidative stress, telomere length, epigenetic remodeling, etc etc. The point here is that lifespan is coded as a developmental program which derives from the genetic blueprint and all the molecular activities that both derive from it and give rise to it. If that wasn't the case, median lifespans of different species wouldn't be so different. Why is it considered obvious why embryological development in a given specie has a fairly fixed timespan, but not why the specie also has a more or less defined lifespan? Especially with so much evidence pointing to it being a genetic program, and so much more having been published since I started this thread back in 2009!



The reason is because genes have function giving way to mechanism. What you are proposing has nothing tangible to test. Magic genes cause aging?
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Re: Science of Ageing

Postby BioWizard on January 15th, 2017, 5:22 am 

Ok SciKen, go ahead and show me where I said (or even implied) that genes don't have function giving way to mechanism. Better yet, show me where exactly I invoked anything remotely resembling magic, or said one thing that goes against what we know about gene function. Did you have one too many of Braininvat's antiaging potion last night or something? If so, good for you - I did too ;)
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Re: Science of Ageing

Postby BioWizard on January 15th, 2017, 7:57 am 

So again, why is it so easy to accept that embryological development follows a faily preset timespan due to genetic programming, but so difficult to accept the same about adult development (i.e. lifespan), >despite< lots of evidence (a lot of which I've referenced in this very thread) demonstrating that it is indeed a genetic program?

I propose that the answer to my question is the same for most defunct theories in academic science that take way too long to die - stakes in funding and publication. :D The sooner we abandom failed assumptions though, the sooner we can be on the right side of both of those things.
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Re: Science of Ageing

Postby vivian maxine on January 15th, 2017, 8:55 am 

Aging is a risk factor of living.
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Re: Science of Ageing

Postby BioWizard on January 15th, 2017, 9:25 am 

vivian maxine » 15 Jan 2017 07:55 am wrote:Aging is a risk factor of living.


Viv, you sure you don't have that backwards? :D
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Re: Science of Ageing

Postby SciameriKen on January 15th, 2017, 9:34 am 

BioWizard » Sun Jan 15, 2017 11:57 am wrote:So again, why is it so easy to accept that embryological development follows a faily preset timespan due to genetic programming, but so difficult to accept the same about adult development (i.e. lifespan), >despite< lots of evidence (a lot of which I've referenced in this very thread) demonstrating that it is indeed a genetic program?

I propose that the answer to my question is the same for most defunct theories in academic science that take way too long to die - stakes in funding and publication. :D The sooner we abandon failed assumptions though, the sooner we can be on the right side of both of those things.


Your model lacks "how" aging occurs. The only evidence you have in this thread is a few genes that we can tinker to increase lifespan. So please expand your explanation of your model a bit more. To phrase it another way - if aging is a coordinated event, what would I look for to stop it?
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Re: Science of Ageing

Postby vivian maxine on January 15th, 2017, 9:39 am 

BioWizard » January 15th, 2017, 8:25 am wrote:
vivian maxine » 15 Jan 2017 07:55 am wrote:Aging is a risk factor of living.


Viv, you sure you don't have that backwards? :D


Well, there is that, too. :-)
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Re: Science of Ageing

Postby BioWizard on January 15th, 2017, 9:48 am 

SciameriKen » 15 Jan 2017 08:34 am wrote:
BioWizard » Sun Jan 15, 2017 11:57 am wrote:So again, why is it so easy to accept that embryological development follows a faily preset timespan due to genetic programming, but so difficult to accept the same about adult development (i.e. lifespan), >despite< lots of evidence (a lot of which I've referenced in this very thread) demonstrating that it is indeed a genetic program?

I propose that the answer to my question is the same for most defunct theories in academic science that take way too long to die - stakes in funding and publication. :D The sooner we abandon failed assumptions though, the sooner we can be on the right side of both of those things.


Your model lacks "how" aging occurs. The only evidence you have in this thread is a few genes that we can tinker to increase lifespan. So please expand your explanation of your model a bit more. To phrase it another way - if aging is a coordinated event, what would I look for to stop it?


Modulating gene expression has yielded much more robust effects on aging rates and lifespans than antioxidants and telomerases. Organisms of a given specie appear to develop and age at preset rates. What kind of evidence are you lacking exactly to see that it's not mere thermodynamic decay?

Oh, and let's not forget that altering gene programs can hault and even reverse mechanisms of thermodynamic cellular decay.
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Re: Science of Ageing

Postby BioWizard on January 15th, 2017, 10:00 am 

By the way, why stop where you are SK? Why not extend your thinking to suggest that embryological and postnatal development are not coordinated events? Because as far as I know we haven't fully figured out how to completely control those either. Are they also passively driven by entropy? Or perhaps magic?
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Re: Science of Ageing

Postby BioWizard on January 15th, 2017, 10:09 am 

I have to say I find it absolutely stunning that we're still having this discussion given the current state of knowledge and everything that has been published in the last five years!!!
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Re: Science of Ageing

Postby SciameriKen on January 15th, 2017, 9:11 pm 

BioWizard » Sun Jan 15, 2017 2:09 pm wrote:I have to say I find it absolutely stunning that we're still having this discussion given the current state of knowledge and everything that has been published in the last five years!!!



Don't go NoShips on me Bio - let's keep it to one entry per response :D

I'll keep my question out there since you avoided it - how does aging occur? Do you have anything beyond "genes" do it? Creationism nicely explains how we came to be - but generates few testable hypotheses beyond that - and similarly so does the Bio model of perpetual embryonic aging :)
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Re: Science of Ageinge

Postby BioWizard on January 16th, 2017, 8:09 am 

You understand the difference between falsifying a hypothesis and constructing a predictive model, do you not? What I set out to do here was to explore which of the proposed processes (oxidative damage, telomere length, gene expression/signaling programs) are controllers of aging, and which are consequence of it. I think to that point, I've provided more than enough evidence to falsify your hypothesis that oxidative damage is an upstream causative trigger of organismal aging and to support the hypothesis that genetic programs are the upstream driver, and that they trigger the downstream mediators which include, amongst other things, your precious oxidative damage. This was recently most clearly demonstrated by the observation that reprogramming the cells through transient expression of the four transcription factors indeed reverses, amongst other manifestation of aging, oxidative damage to the cells (hint: that's one of the hypotheses that have been tested: result? reject null hypothesis). Comparing what I've done here to a creationist proposal is absurd and a strawman, the likes of which one encounters in a creationist's anti-evolution rhetoric. So congrats on that SK.

And no, I did not avoid any of your questions. You, however, avoided all my perinent questions and went on to - intentionally or unintentionally - suggest that hypothesis testing cannot be complete without a fully predictive working model, which is a bit absurd. Mind you, this doesn't mean that some precise knowledge about exactly what genes trigger exactly which pathways in exactly what chronological order to mediate the progession of the aging process isn't already available, just that I don't personally have it off the top of my head and - more importantly - that it's irrelevant to the subject of the OP. I will, however, do some literature searches and try to find some specifics for you, so you won't even have that crutch to stand on. Though you can probably start with the very last paper I posted in this thread.

In the meantime, you can answer some of my questions:

1- Do you have all the specifics on how genes control embryological development? If not, should I - in your opinion - take that to mean that genes do not control development?

2- If aging is not a genetically controlled process, how do you explain the difference in median lifespan of different species?

3- If aging is not a genetically controlled process, why does the germline not age?

4- If aging is not a genetically controlled process, how are we able to take terminally differentiated cells and immortalize them by manipulating their gene expression programs?

5- If aging is driven by oxidative damage, why does lifespan remain largely unaffected when oxidative damage is quenched (which by the way, is starting to look like it could be a bad thing - not a good thing - for health, let alone aging)? (this is another hypothesis that was tested - result: reject hypothesis)

6- If aging is driven by telomere length, why does extending telomeres not extend lifespan? (this is another hypothesis that was tested - result: reject hypothesis)

7- If aging is not driven by a genetic program, then how come expressing genes that alter genetic programming of a cell have thus far shown the biggest effect on organismal aging reversal and lifespan extension we've seen thus far. (last hypothesis tested - result: reject null)

When you give me answers to these questions (many of which I've already mostly or partially answered), this conversation might become worth continuing again.
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Re: Science of Ageing

Postby BioWizard on January 16th, 2017, 9:26 am 

SciameriKen » 15 Jan 2017 08:11 pm wrote:I'll keep my question out there since you avoided it - how does aging occur? Do you have anything beyond "genes" do it?


It's been a white since I started this thread, so a refresher might be in order. SK, here are my first two posts in this thread, and a key bit that Paralith highlighted. They outline the overall model I had in mind, for which I decided to investigate the three hypotheses (aging is caused by oxidative damage, aging is caused by telomere shortening, aging is a genetically controlled program much like development) and set out to look for studies that test them. Here are the posts:

BioWizard » 29 May 2009 11:25 pm wrote:Very often, I hear people talk about ageing in terms of entropic decay, as if ageing of a multicellular organism is nothing more than wear and tear, a machine getting rusty over time until it breaks down. Well, it's not. Ageing is an active cellular program, much like differentiation and apoptosis. Cells age after they differentiate and turn senescent. Germ cells don't age, and because they maintain genetic continuity over generations, ageing would defeat the purpose and thus did not evolve to occur in those cells. Other cells that evade the ageing program are cancer cells (which highlights an important role for cellular ageing in multicellular organisms - tumor control).

So many misconceptions surround this subject, a lot of which are viciously capitalized on my the cosmetic and food industry. Antioxidants and reactive oxygen species. Oxidative damage, symptom or cause? How do telomeres factor into all of this?

A lot of questions with no single reliable source of conclusive answers. Because of that, I've decided to start this thread, in which I wish to explore the most recent scientific findings on the subject and tease out information from misinformation, fact from media/industry myth. Everyone is welcome to contribute provided only credible sources are used (only papers from peer reviewed journals). Questions are welcome along the way, but please try not to derail the thread with too many questions. If you would like to discuss any particular point with any details, please start a separate thread for it.


BioWizard » 30 May 2009 06:39 am wrote:
Paralith wrote:but part of his theory involves an increasing cost to maintenance and repair of somatic structures as the life course goes on - over time the body experiences various insults from disease, injury, stress, and the build up of metabolic wastes, and the cost of maintaining a well-functioning body in the face of these insults increases over time. At least, that's how I understand it, and I could be understanding it wrong. So Bio, are you basically saying that this isn't true?


I'm saying it might be missing the point, and that ageing is a lot more than entropic decay and simple wear and tear. When you're young, your injuries get repaired faster, and then slower and slower as you grow older, until they stop and rapid breakdown kicks in. In cells, decay is always taking place. Proteins are being unfolded and degraded, DNA and RNA are being oxidized and turned over, and so on. Everything is constantly decaying and turned over, starting from when you are a single cell. However, the difference between cells in a young organism and cells in an old organism is that in the latter, the production of new cellular components to replace the damaged ones slows down, and the rate of elimination of damaged components slows down too, leading to accumulation of oxidized and damaged molecules - aka cellular ageing. On the level of tissue, decay and turn over is also no stranger. When you are young, your cells decay and die, probably at even a higher rate than when you are old. However, the supply of cells simply gets replenished faster, and the tissue remains healthy (assuming no disease factors). As one ages, the rate of producing new cells seems to slow down, and since the new cells produced are also tired ones, with accumulated damage (from the previously mentioned phenomenon of cellular ageing), the tissue gets less and less healthy over time. Which is probably why organs with lowest rates of cellular turnover are the most suscupetible to tissue/organ ageing when cellular ageing programs kick in.

As for cost/maintenance issues, I think that is more related to the evolutionary processes that shape the ageing phenomenon (clearly not all organisms age the same, and some don't at all), and I would like to explore that too later, but probably in a separate thread in Biology. Here, I want to focus on the mechanisms and biochemical triggers of the ageing process (program?).

Paralith wrote:I have to say that seems kind of counter-intuitive to me. We see every day humans experiencing increasing decrepitude as they age, even long before they enter stages we would call old or elderly. Children and teenagers seem to bounce back from injury much more easily than thirty and fourty year olds. You're saying this is all specifically programmed, and not (at least partially) the result of wear and tear on the body?


Wear and tear and entropic decay are not the cause of ageing, rather they're a property of ageing, a mediator. But entropic decay is a property of the universe and everything in it. Clearly, however, not everything decays all the time, and you can go in the opposite direction if you provide sufficient enthalpy to counteract the effect of entropy. So it's not like entropy kicks in at increasing amounts as one ages, it's always there. Everything decays unless you put in energy to replenish and repair. What does change as you age however is the rate at which new components are made and damaged components are removed, and we know that rates of cellular events depend on the activity of the enzymes catalyzing them. This can be affected by the rates of expression of the genes coding them, the structure of the substrates, and the rate of degradation of the enzymes, amongst other things, all events that are known to be controllable by cellular programs. If it were simply passive entropic decay, all cell types would age the same way and at the same rate, but they don't. Thus, equating entropic decay with ageing is equating a phenomenon with one of its symptoms, and possibly overlooking the real triggers and mechanisms. These are some of the ideas and controversies I would like to explore by checking them against the scientific literature.


Paralith » 30 May 2009 10:39 am wrote:
BioWizard wrote:If it were simply passive entropic decay, all cell types would age the same way and at the same rate, but they don't. Thus, equating entropic decay with ageing is equating a phenomenon with one of its symptoms, and possibly overlooking the real triggers and mechanisms.


Thank you Bio, your post cleared that up perfectly, and I especially like the section I quoted above.
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Re: Science of Ageinge

Postby SciameriKen on January 16th, 2017, 10:01 pm 

BioWizard » Mon Jan 16, 2017 12:09 pm wrote:You understand the difference between falsifying a hypothesis and constructing a predictive model, do you not? What I set out to do here was to explore which of the proposed processes (oxidative damage, telomere length, gene expression/signaling programs) are controllers of aging, and which are consequences of it



My apologies - I thought you were attempting to describe a gene based model of aging. As far as what you set out to accomplish? I don't think you are there yet. You still need to establish whether the "gene expression/signaling program" is a set program that specifically induces the aging phenotype, or whether it is simply the defense against the hallmarks of aging. If it is solely the latter than the controller of aging is really nothing more than a chicken and egg scenario (Hallmarks causing damage or genes defending against damage). The fact that this recent reprogramming reduced some hallmarks of aging is supportive, however, total life extension was only 30% and I do not have the paper in front of me - but were they turning the genes on and off or was it just a one time thing?

Seeing as you do not have a model of aging, I will now apply my model to your questions and we'll see how far I get...

1- Do you have all the specifics on how genes control embryological development? If not, should I - in your opinion - take that to mean that genes do not control development?
I think I quoted away the context for this first one - but it doesn't seem important here...

2- If aging is not a genetically controlled process, how do you explain the difference in median lifespan of different species?
Under my model - as aging occurs heterochromatin formation reduces signaling from genes that are protective against the hallmarks of aging. Median lifespan is the summation of all genetic controls of heterochromatin formation as well as the efficiency of genetic systems against the hallmarks of aging. We live 77 years longer than a mouse because our genetic systems are just that much more effective.

3- If aging is not a genetically controlled process, why does the germline not age?

If heterochromatin formation is a major contributor to the aging phenotype, then germline cells immune due to reprogramming at the initiation of development. Furthermore as the organism develops essentially all DNA, RNA and proteins are generated de novo, and thus have limited exposure to the damage of such things as oxidative damage, DSBs, etc..

4- If aging is not a genetically controlled process, how are we able to take terminally differentiated cells and immortalize them by manipulating their gene expression programs?

The manipulations target the hallmarks of aging (e.g. allowing expression of telomerase to extend telomeres), thus it is once again the chicken and egg scenario discussed above as far as what is the driving process of aging.

5- If aging is driven by oxidative damage, why does lifespan remain largely unaffected when oxidative damage is quenched (which by the way, is starting to look like it could be a bad thing - not a good thing - for health, let alone aging)? (this is another hypothesis that was tested - result: reject hypothesis)

ROS has important roles in signaling, thus complete abrogation of oxidative damage is a bad thing. aberrant ROS signaling damages macromolecular structures which could have harmful effects - however, the overall harm to lifespan due to oxidative damage seems to be not as great as hypothesized. Might it still contribute to the overall aging phenotype, particularly in concert with other hallmarks of aging?

6- If aging is driven by telomere length, why does extending telomeres not extend lifespan? (this is another hypothesis that was tested - result: reject hypothesis)
Really?
Expressing telomerase increasing lifespan about ~15-20% in mice
https://www.ncbi.nlm.nih.gov/pubmed/22585399

Rate of telomere shortening predict lifespan in mammals
https://www.ncbi.nlm.nih.gov/pubmed/23022483

Reduction of telomerase shortens lifespan of zebrafish
https://www.ncbi.nlm.nih.gov/pubmed/23349637
https://www.ncbi.nlm.nih.gov/pubmed/23744274

Telomeres are just another hallmark of aging and the regulation of which is another contributor to overall lifespan of the organism.

7- If aging is not driven by a genetic program, then how come expressing genes that alter genetic programming of a cell have thus far shown the biggest effect on organismal aging reversal and lifespan extension we've seen thus far. (last hypothesis tested - result: reject null)


Genes confer resistance and recovery from hallmarks of aging - back to chicken and egg problem.
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Re: Science of Ageing

Postby BioWizard on January 16th, 2017, 10:12 pm 

SciameriKen wrote: We live 77 years longer than a mouse because our genetic systems are just that much more effective.


Very good SK! Looks like your model is now returning it all to the genes as well, in some way or the other. You're more or less saying exactly the same things, but insist that they are called differently. Relative effectivess of our genes makes us live longer than mice? Close enough, I'll take it! I mean, I really don't care what you call it as long as you get it. Some people find it harder than others to accept that they were wrong about something. So whatever makes you feel better. Let's call it gene effectiveness instead of gene program. Rememeber that my model talks about diminishing equilibrium between replenishment and tear, so you've really not strayed far at all.

Excellent. Now, instead of thinking it can be done by doping on antioxidants or overexpressing telomerases, we can start digging for the underlying genetic programs (err I meant efficiencies sorry!) that make us age "more effectively" than mice (or make mice age "less effectively" than us), and try to figure out how to improve this "efficacy", and whether we can "switch it on" for extremely extended periods of time (perpetually?). Maybe while we're at it, we can also try to understand better how cellular aging, cellular turn over, tissue aging, and organismal aging all relate to one another instead of lumping them altogether and explaining them all in simplistic terms.

Great to be finally making progress!!!
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Re: Science of Ageing

Postby ronjanec on January 16th, 2017, 10:26 pm 

SciameriKen » Sun Jan 15, 2017 7:11 pm wrote:
BioWizard » Sun Jan 15, 2017 2:09 pm wrote:I have to say I find it absolutely stunning that we're still having this discussion given the current state of knowledge and everything that has been published in the last five years!!!



Don't go NoShips on me Bio - let's keep it to one entry per response :D

I'll keep my question out there since you avoided it - how does aging occur? Do you have anything beyond "genes" do it? Creationism nicely explains how we came to be - but generates few testable hypotheses beyond that - and similarly so does the Bio model of perpetual embryonic aging :)


"Don't go NoShips on me Bio...": Good one SK. That was really funny!
Last edited by ronjanec on January 16th, 2017, 10:28 pm, edited 1 time in total.
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Re: Science of Ageing

Postby BioWizard on January 16th, 2017, 10:27 pm 

Three posts in a row? That doesn't even come close to going NoShips.

Calling it creationism on the other hand, now THAT was funny!
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Re: Science of Ageing

Postby ronjanec on January 16th, 2017, 10:32 pm 

BioWizard » Mon Jan 16, 2017 8:27 pm wrote:Three posts in a row? That doesn't even come close to going NoShips.

Calling it creationism on the other hand, now THAT was funny!


No one said that there still wasn't room for improvement in this area BioWizard. :)
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Re: Science of Ageing

Postby BioWizard on January 16th, 2017, 10:33 pm 

ronjanec » 16 Jan 2017 09:32 pm wrote:
BioWizard » Mon Jan 16, 2017 8:27 pm wrote:Three posts in a row? That doesn't even come close to going NoShips.

Calling it creationism on the other hand, now THAT was funny!


No one said that there still wasn't room for improvement in this area BioWizard. :)


Unlikely.
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Re: Science of Ageing

Postby ronjanec on January 16th, 2017, 10:37 pm 

Yes, "greatness" is very often pursued, but very rarely attained. :)
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Re: Science of Ageing

Postby BioWizard on January 16th, 2017, 10:38 pm 

Indeed. Any thoughts about aging ron?
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