149 replies to this topic

[stefan_001]

@sthira what if it is not about repair? Perhaps the human body internal state is simply instable and processes go pear shaped. Organ damage follows. There is no intelligence inside a cell or the wider organism, its just a balance of processes and some will start to run away. Replenish helps us steering the "process" back to "safe" terretory.

[xEva]

Assuming Mother Nature gradually reduces humanity's NAD+ because Mother Nature doesn't care about us after we're done reproducing -- boo hoo -- then we should seek to repair the cause of the depletion organ by organ. I think that's where the science is going -- or should be -- repair rather than just replenish with precursors.

 

looks more like Mother Nature cares very much that we die in a timely manner after we're done reproducing -- so that new --and maybe even better adapted!-- individuals may fill the void.

 

I partially agree with Stefan, that "There is no intelligence inside a cell or the wider organism," in the sense that a 'dumb program' governs a cell's behavior and the organism as a whole -- and it does so according to the clues in its environment. I hope we could find a way to trick an older cell 'to think' that it's in a much younger environment than it id and that it's gotta keep up -- this should turn on the repairs and restore youthful phenotype, no?

Edited by xEva, 08 December 2018 - 03:02 AM.

[Oakman]

looks more like Mother Nature cares very much that we die in a timely manner after we're done reproducing -- so that new --and maybe even better adapted!-- individuals may fill the void.

 

I partially agree with Stefan, that "There is no intelligence inside a cell or the wider organism," in the sense that a 'dumb program' governs a cell's behavior and the organism as a whole -- and it does so according to the clues in its environment. I hope we could find a way to trick an older cell 'to think' that it's in a much younger environment than it id and that it's gotta keep up -- this should turn on the repairs and restore youthful phenotype, no?

 

I think Mother Nature's design just gets us going in a benign fashion (birth) and lets us unwind from there. twisting on our own DNA, as it were. We do the rest.

 

I'd venture aging is a combination of two over-riding factors, namely, 1st we just wear out like any other physical mechanism as things get messed up from constant use with no 100% good repair mechanism available. and 2nd, there are internal clocks that program DNA activation/deactivation which guides processes in one direction (aging) regardless of use. As to why the clocks exist, and why they are programed the way they are - now that's the puzzle.

 

Repair is helpful, but reprogramming the clocks is essential to solve aging!

[stefan_001]

@oakman the idea there are clocks is I think optimistic. Personally I believe those are emergent effects of an endless amount of feedback loops. xEVA view is closer to mine, how to influence the cell environment to make ut behave like a young cell.

[OP2040]

Count me as one of the fighters and one of the optimists, but with a lot of compassion and understanding for the pessimists.  I don't think the idea of "irresistible damage/entropy" is even plausible for biological systems.  It is very clear that other aspects of life history are highly programmed and tightly controlled.  Everything from reproduction to young adulthood happens like clockwork for the vast majority of the billions of people on the planet, not to mention animals.  So in a way it is interesting that our mindset suddenly switches when it comes to old age.  There can only be two possibilities for why youth is not maintained indefinitely.  First is the selection shadow.  If that is the case, then applying youth factors to old people would be enough to get the job done.  Second would be an active aging program, in which case we would have to stop the program in its tracks.  Or it could be some subtle combination of those two.  But one thing is for sure, it has to be one of those two, else aging would be a multi-generational affair and life never would have made it this far.

 

If I had to guess as to what the program is, I am still saying epigenetics.  But what does that even mean?  I was inspired recently by a simple wiki article on "retinal regeneration" that I will post below.  But reading that made me think that the process is twofold, like so:

1. Gene Expression

    a. Epigenetic marks - these are added to shut off the gene expression that occurs in youth.  They are sometimes added as a mark of damage, but not always.

    b. De-differentiation - Once the marks are cleared, the genetic material is now available within somatic cells to allow for de-differntiation, which brings tissue repair.

 

Of course there are many more details than this to be ironed out.  Mainly, it needs to be completely controlled so that the de-differentiation can be stopped at the appropriate time.  But one of the studies referenced in the wiki article seems to indicate that it is largely just that simple, at least for an immune privileged organ like the eye.  Basically, in mice, they opened up the chromatin of muller glial cells that are known to de-differentiate in animals that do have retinal regeneration with Trichostatin A, an HDAC inhibitor.  Then they actively promoted the correct genes to accomplish that dediff, as it happens in regenerative animals.  And voila, adult mouse retinal regeneration!

 

This kind of thing is so very, very close I think.  And regenerating a failing organ would have a huge public impact that our vague discussions about aging just won't have.  It will not take decades to prove, and at that point, no reasonable person would be able to say that all the problems that come with old age are inevitable and irreversible.

 

https://en.wikipedia...al_regeneration

 

The fact that this is not being tried on someone that has lost 99% of their eyesight from macular degeneration boggles the mind.  What exactly is the risk?  But that is another discussion.

 

[xEva]

oh! that sounds interesting We should split this discussion into the aging theories section.

 It'd be interesting to know what the forum consensus on this matter is, at the moment. Maybe we should do a poll?

 

and I tend to agree with both of you guys. There is no doubt that there are clocks and they govern the development. Otherwise individuals would grow, reach sexual maturity and age at different rates (rather than most falling into 'a norm'). If one is to accept that aging is programmed then it is an extension of the development (and it is accomplished by ever-growing in persistence attenuation of repairs). I also think it'd be easier to identify the pro-aging signals than mess with the clocks themselves.

 

PS

OP2040@ sounds right on the money! -- I did not see it, coz we posted at the same time.

 

 

Edited by xEva, 08 December 2018 - 07:27 PM.

[MikeDC]

I think there are 3 pieces in anti aging. The first stage of ageing is the normal tear and wear due to oxidation stress. This represent the period from 25 to 40. At 40, enough damage is done and enough inflammation has accumulated that NAD+ has been depleted significantly. We currently don’t have an effective method to deal with this. The second stage of aging is after NAD+ is significantly depleted and age related diseases start to accumulate. This stage is ageing is exponential. We have found the preliminary solution against this second stage exponential ageing. The solution is using NR to increase NAD+ to youthful levels. The third part of anti aging fight is to create new stem cells after the body has used up all existing ones. We are not that far from a solution for this. Normal cells can be reprogrammed easily to stem cells. When cells are old, NAD+ supplementation is also needed for this transformation process. My guess is we are 20 years away from a mature medical procedure.

[stefan_001]

oh! that sounds interesting We should split this discussion into the aging theories section.

 It'd be interesting to know what the forum consensus on this matter is, at the moment. Maybe we should do a poll?

 

and I tend to agree with both of you guys. There is no doubt that there are clocks and they govern the development. Otherwise individuals would grow, reach sexual maturity and age at different rates (rather than most falling into 'a norm'). If one is to accept that aging is programmed then it is an extension of the development (and it is accomplished by ever-growing in persistence attenuation of repairs). I also think it'd be easier to identify the pro-aging signals than mess with the clocks themselves.

 

Humans always seek logical explanations but in my view growth and aging are not programmed. The body is just full of resonance systems and because nobody corrects them eventually they go off track. Growth is a phase of unbalance upon which the body comes in a period of equilibrium that eventually goes peer shaped as well. There is no intelligence, no programming -  best random spaghetti code that combined behaves a certain way - but that doesn't mean it cannot be patched up for a while.... Even DNA is just an outcome of millions of years of random, unplanned experiments - its a polymer of nucleic acid that because of inter molecular forces pulls into a cool looking helix that by accident gave it wonderful properties. Yeah its a miracle that humans would actually form out of a random process but again millions of years and billions of parallel "organism" forming activities around the planet in parallel - just statistics..
 

Edited by stefan_001, 08 December 2018 - 07:40 PM.

[OP2040]

oh! that sounds interesting We should split this discussion into the aging theories section.

 It'd be interesting to know what the forum consensus on this matter is, at the moment. Maybe we should do a poll?

 

and I tend to agree with both of you guys. There is no doubt that there are clocks and they govern the development. Otherwise individuals would grow, reach sexual maturity and age at different rates (rather than most falling into 'a norm'). If one is to accept that aging is programmed then it is an extension of the development (and it is accomplished by ever-growing in persistence attenuation of repairs). I also think it'd be easier to identify the pro-aging signals than mess with the clocks themselves.

 

PS

OP2040@ sounds right on the money! -- I did not see it, coz we posted at the same time.

 

Yes! an aging theory thread and poll would be great.  At the end of the day a poll is just fun, as science is not a democracy.  However, there is wisdom in the crowd, especially a relatively informed one such as we have here.

 

I can't help but think that the answer is actually out there already.  It's just hard to see in the mess of all these studies coming from different angles.   

[OP2040]

Humans always seek logical explanations but in my view growth and aging are not programmed. The body is just full of resonance systems and because nobody corrects them eventually they go off track. Growth is a phase of unbalance upon which the body comes in a period of equilibrium that eventually goes peer shaped as well. There is no intelligence, no programming -  best random spaghetti code that combined behaves a certain way - but that doesn't mean it cannot be patched up for a while.... Even DNA is just an outcome of millions of years of random, unplanned experiments - its a polymer of nucleic acid that because of inter molecular forces pulls into a cool looking helix that by accident gave it wonderful properties. Yeah its a miracle that humans would actually form out of a random process but again millions of years and billions of parallel "organism" forming activities around the planet in parallel - just statistics..
 

 

It's really an uphill argument to say that growth and development are not programmed.   Humans seem to hit each stage of the developmental cycle at a very specific time and there is almost never an exception.  Every pregnancy ends at about the same time.  Every preteen goes through puberty at roughly the same time.  Aging does seem a little different in that you can speed it up somewhat.  But even there, the entire world seems susceptible to about the same age-related diseases.  Even something as banal as myopia occurs within a pretty tight schedule for almost everyone.  The only reason aging doesn't look amazingly programmed to us is because we take these things for granted.  Also, there is probably a psychological element to it as we would prefer to think we have some sort of control. 

 

there are other things that don't make sense according to any damage theory, such as hormesis.  Mitteldorf has pointed this out and we tend to keep ignoring things like this because they aren't intuitive to us.  My favorite example the calorie restriction concept itself.  It used to be thought this worked by simply limiting damages, but that was disproved.  Now it is thought that it is a signal that upregulates repair signals.  But very few aside from Mitteldorf have pointed out how really strange it is that more food is a bad thing for an animal. 

By any measure of logic, more energy input into an open system should result in a more vigorous and repaired system, but alas this is not the case.

[Michael]

Development is of course programmed — that is totally not debated. A small number of people argue that aging is programmed, but it is fairly clearly and almost tautologically not. The design and building of cars is a planned and organized process; despite conspiracy theories, the falling-apart of cars is not (and Darwinian mechanism exclude Intelligent Design in any case).

 

Anyway, unless anyone objects, I'll follow xEva's suggestion supported by others to cleave off this off into the Aging Theories Forum.

[Oakman]

By any measure of logic, more energy input into an open system should result in a more vigorous and repaired system, but alas this is not the case.

 

There is no logic, by any measure that this is or could be true. Take a look at the excess 'energy' consumed by the majority of the US population. Excess energy is a burden, a toxin, and causes disruption in homeostasis.

[stefan_001]

Development is of course programmed — that is totally not debated. A small number of people argue that aging is programmed, but it is fairly clearly and almost tautologically not. The design and building of cars is a planned and organized process; despite conspiracy theories, the falling-apart of cars is not (and Darwinian mechanism exclude Intelligent Design in any case).

Anyway, unless anyone objects, I'll follow xEva's suggestion supported by others to cleave off this off into the Aging Theories Forum.

Actually the falling apart of cars is very much planned. And the building of a human is not planned process, just as an ant hill is not a planned process - yet all ant hills look similar.

[OP2040]

Well it looks like we’re going to have some great debates. Whoever makes the aging theories thread post the link here and I’ll refrain from any more commenting on it until then.

I have a new batch of Fisetin coming in, thinking about taking it as a daily and taking frequent breaks, partly due to cost and partly because it’s just good to do that.

[Rocket]

Actually the falling apart of cars is very much planned. And the building of a human is not planned process, just as an ant hill is not a planned process - yet all ant hills look similar.

100% totally wrong. Engineers are not capable of planning how and when something as complex as an automobile will fall apart. We can barely manage bringing them to market on time functioning as planned, let alone sit around planning how and when they will fail. Automobiles and their components are typically tested to 10 years durability. Some companies, longer. How they fail over time is totally random, like aging, but yet like aging they all follow a pattern... Almost exactly like aging. Wipers and tires and brakes typically fail first. So on and so forth. If you think engineers sit around and plan on how their cars will fail and when, you've seen too many movies and have no clue what engineering a complex vehicle entails. Companies don't spend millions of dollars to make sure their cars fall apart. They do spend billions to bring one to market fro a sketch.

I would argue that ant hills are planned. Maybe ants don't build to CAD data, but they are following a genetic roadmap.

Same with building a human.

Humans build cars to last 10 years, then after that who cares. Nature builds humans to last around 30 years and then who cares.

[Kevnzworld]

To say aging isn’t programmed ignores the obvious. Menopause happens for 90% of women within a 5 year window, as does puberty.
It’s not just by chance that most non obese, non diabetic relatively healthy people that have escaped an early demise die within a five year window. ( 87-92 ) Sure there’s a small percentage that make it a few years more .
But if life wasn’t programmed there would be a lot more variability in lifespan as there is in lifestyle.
A car well maintained can last indefinitely, a person not so much.

[sthira]

I guess I don't understand why it matters if aging is programmed or not. When something goes wrong, you break a bone or you get dementia, do you really care if it happened because of some complicated ancient programming? Or do you just want the damage repaired -- quickly, efficiently, and at an fair price -- so you can go living your happy and sad life?

This thread is about fisetin and its potential role in senescent cell management. Why care if dark little disease parties formed programmatically or were the result of normal bodily activities? We want them gone -- gtfo stupid half-dead cells spewing filth -- does fisetin work or not?

Now if you say -- I care about this debate because understanding my body's intricate programming, and then learning how and when to manipulate that programming is important to accomplishing goals of age reversal, then fine. Carry on. But think that'll happen anytime soon? Think this is a job for DeepMind? I've read stated here that some believe humanity will solve aging before we understand it.

Regarding the car analogy, we get how cars work because we made them. So then we fix them. But will we ever understand how humans were made, why age breaks bodies, and is that understanding even necessary in order to repair an arthritic ankle? Repair the immune system causing the arthritic ankle -- start with thymus regeneration. The thymus was programmed to involuted at around 20-years of age or so, great: now regenerate the thing to cure the arthritis.

Obviously none of these thoughts are my own and I'm another squawking parrot, lol, but who cares: I just want aging reversed to get the hell out of here and go see what's going on in Proxima Centauri.

[Mind]

oh! that sounds interesting We should split this discussion into the aging theories section.

 It'd be interesting to know what the forum consensus on this matter is, at the moment. Maybe we should do a poll?

 

and I tend to agree with both of you guys. There is no doubt that there are clocks and they govern the development. Otherwise individuals would grow, reach sexual maturity and age at different rates (rather than most falling into 'a norm'). If one is to accept that aging is programmed then it is an extension of the development (and it is accomplished by ever-growing in persistence attenuation of repairs). I also think it'd be easier to identify the pro-aging signals than mess with the clocks themselves.

 

PS

OP2040@ sounds right on the money! -- I did not see it, coz we posted at the same time.

 

I thought for sure that we had a poll about aging theories. I did a brief search could not find anything. Anyone else remember seeing a poll from a few years ago?

[Rocket]

Take 2 pieces of raw meat, place them outside in the sun for a week. The rotting process is totally random in the cells and tissues of the meat, yet both will rot at almost exactly the same rate in the same manner. Is that programmed into the meat to rot like that? No. It is random. But it all happens right on time between the two entities. Just like menopause and puberty.

 

 

 

 

[sthira]

Now if you say -- I care about this debate because understanding my body's intricate programming, and then learning how and when to manipulate that programming is important to accomplishing goals of age reversal, then fine. Carry on. But think that'll happen anytime soon? Think this is a job for DeepMind? I've read stated here that some believe humanity will solve aging before we understand it.

Actually, my phone is already doing a pretty good job of learning my programming. It now seems to know where I'm going before I do -- check google maps, fuck it, it's indicating my predictable daily directions, my behavior (gi coffee shop, buy iced coffee, smile). And when I walk away not much imagination is required before it's analyzing my walking gait, why the ball of left big toe is slightly pidgeoning, causing inner left arch to not lift as high so the other leg's right hip is slightly thrown left, soon it'll send me tiny electrical pulses I won't even notice that help straightening the walking alignment as I blindly sip coffee.

Also it's learning what I want to read (onion) and the camera phone is staring at my face, calculating micro muscles I don't notice, knowing now my heart rate based on those motions, my blood's pounding pressure, it knows specific numbers of pupil dilations, and soon continuous glucose monitors, IGF-read outs, whatever we want or don't want, and I think this is all great, but also so fucked up. We're total puppets. Determining programming patterns won't be that hard.... indicating we never were really in control of anything anyway, including walking, all thoughts right now, the technology is just about ready to make it quite plain that all that free will shit really was quite delusional.

[OP2040]

There is no logic, by any measure that this is or could be true. Take a look at the excess 'energy' consumed by the majority of the US population. Excess energy is a burden, a toxin, and causes disruption in homeostasis.

 

That is exactly the point that Mitteldorf tries to get across with pointing this out.  In an open system that feeds off of external energy to run it's processes, more calories should result in better functioning, not worse.  The fact that the opposite is true is some evidence that bodily processes and aging are highly programmed. 

 

Metaphors have the potential to enlighten, but they also have the potential to severely impair the search for understanding.  And IMO, the car metaphor has done much damage in our search for the truth of aging.  Biological systems are nothing like cars at all.  Cars are not an open system that take in free energy to drive processes.  Cars are essentially dead when turned off.  Cars have no memory of life history.  The metaphor could be closer to the truth if cars had a team of mechanics working around the clock to keep them in top condition.  But then with that metaphor the question has to be asked, why do the biological mechanics go on strike?  There is no logical reason for them to do so unless there is some evolutionary benefit to imposing a strike (aging and disrepair) on individual soma's.

 

It is true that programming is yet another metaphor. And I find it fascinating that these two metaphors correspond to two era's in human history, first the industrial (mechanical) revolution, and now the information revolution. It seems we humans are very susceptible to historical metaphors of the times, which can be very helpful but also at the same time very limiting.

 

It makes one wonder, what potentially useful metaphors are we missing?  One this is for sure, biology is incredible and unique, and maybe none of these metaphors do it justice.  Unlike mechanics, energy and information, biology has not yet seen its era.  It's up next!

[OP2040]

To say aging isn’t programmed ignores the obvious. Menopause happens for 90% of women within a 5 year window, as does puberty.
It’s not just by chance that most non obese, non diabetic relatively healthy people that have escaped an early demise die within a five year window. ( 87-92 ) Sure there’s a small percentage that make it a few years more .
But if life wasn’t programmed there would be a lot more variability in lifespan as there is in lifestyle.
A car well maintained can last indefinitely, a person not so much.

 

I don't have the gift of saying things succinctly, as you clearly do.  This sums up the argument very nicely.

[Mind]

One nice thing about the damage theory of aging is that it is "low-hanging fruit", more easily tested in a shorter time frame than programmed theories of aging. "Fixing damage" could help a lot of people live long enough to benefit from other discoveries in the study of aging.

[OP2040]

Take 2 pieces of raw meat, place them outside in the sun for a week. The rotting process is totally random in the cells and tissues of the meat, yet both will rot at almost exactly the same rate in the same manner. Is that programmed into the meat to rot like that? No. It is random. But it all happens right on time between the two entities. Just like menopause and puberty.

 

This is a very good starting argument.  Basically, essentially stochastic processes can look programmed. 

 

I would respond that the reasoning breaks down with humans because biological systems exercise choices and even reasoning in ones with higher consciousness.  So with humans we have a vast array of different lifestyles, choices and interventions happening all the time.  The two pieces of meat in your analogy are set up in exactly the same way.  However, meat does not rot at the same rate if you freeze it, or if you add preservatives to it, or in different climates, or different microbes.  However, puberty, aging and menopause will happen about the same time despite humans quite varied lifestyles and all but the most radical interventions.  The only question is, are the emerging ways in which we are able to intervene in these previously untouchable developmental cycles characterized by the repair of a damage, or hacking into a program.  Of course, naturally I would say the latter. 

 

We already see in aging that repairing a damage does almost nothing to cure any disease, much less slow down aging.  There are many proofs of this, but I like the Alzheimer's proof the best.  We have now tried and failed to cure Alzheimer's by clearing damages.  And the reason is because many things we call damages in the human body are part of larger processes, whether they be senescent cells, ros and even amyloid.  If you clear out these so called damages, but don't touch the underlying process, the aging process just keeps chugging along like nothing happened.
 

[OP2040]

One nice thing about the damage theory of aging is that it is "low-hanging fruit", more easily tested in a shorter time frame than programmed theories of aging. "Fixing damage" could help a lot of people live long enough to benefit from other discoveries in the study of aging.

 

The problem is it largely has been tried, and to continue trying something that is not working wastes a lot of time and resources.  We spent decades on the mitochondrial theory of aging only to find out that ROS is an important signaling molecule.  We wasted decades and billions of dollars on the amyloid hypothesis of Alzheimer's.  One might say senescent cells offer a good example of the damage theory working out for us, but I completely disagree.  Senescent cell clearance is a good therapy, of that I have no doubt.  But in my way of thinking, it is a powerful therapy because it touches on a huge part of the job that a failing process used to do very well, namely the failing immune system.  With a process/programming way of thinking you can kill 100s of birds with one stone.  Immune system collapse looks very programmed as gene expression supporting the thymus just shuts down,  and we now have quite a few ways to intervene and regrow the thymus for example.  It may not be low hanging fruit but it is orders of magnitude more powerful.

[Oakman]

This talk of various analogies and a youtube video I watched last night got me thinking. Most of the analogies given, like cars and dead meat, etc. are dealing with inanimate objects. There's no programming there, just entropy unfolding. Order to disorder plain and simple. Physical and chemical processes unfolding. No programming, no life. Programming or re-programming any static process is fun and generally productive because the object being worked on is 100% predictable. You change the programming, the outcome can be different.

 

People, and any living thing is vastly different. "Life" of any type by any thing, is really 'Life Force' plus just the right type and amount of energy input to enable biochemical processes to unfold correctly - and all to rail against entropy. That's the difference. Life is a force that attempts to control and reverse decay resulting in aging and fights the natural order of the universe - Entropy!

 

You can take all the components of life, put them together, and you do not get life. Furthermore, you can decode the entire genome of an life form, give it to another scientist and they cannot tell you what it is and what it will look or act like, nor how long it will live. There is something missing still! That elusive 'other' requisite thing is 'Life Force'. You can't buy that on Amazon, but that is the thing we should try to understand, to harness its power, to modify its actions to our benefit. That is the MASTER force that controls and runs the organism from conception to death. And then it's gone.

 

Life force is, however, both faliable and imperfect, and seems to be unable to overcome the external obstacles put against it forever (some amebas and some plants seem to be able to do a creditable job though). What it does do, is work reasonably well managing everything needed for life for a variable time, but then it fails in one or multiple ways.

 

So while we attempt to help out Life Force with its day-to-day problems with oxidation, telomeres, senescence, and the like, we are only giving a helping hand, not (yet) writing new ways that each form of life uses to survive. Low hanging or not, these are the strategies available to us that can offer hope and, sometimes good results against aging. But to conquer aging at its root, some as yet to be discovered force(s), need to be investigated and understood.

 

Lest anyone think I'm venturing into religion here, I'm not. Life Force isn't a soul, but what it is I don't know. And as for analogies, I am a programmer, and a computer expert by trade, so here goes another analogy. These processes we're trying to change, I'll call them subroutines, and because they are fixed and done through gene transcription, they can fail when there is too much damage and chaos to repair. Ergo, we 'age', we break down, we die. So IMHO, the most we can do, given we do not understand what 'Life Force' is and how to deal with it directly to solve these troubling failings, is 'help', not fix, the myriad failing of our bodies inner workings as it simultaneously rails against the universe's ways - and entropy!

 

[OP2040]

I think it's fair at this point to dig a little deeper.  Whichever side you happen to be on, lets get into the details and evidence.  For the damage hypothesis, which damages do you think are most important?  What are the main causes of the where and tear, for example endogenous or exogenous, etc.  For the programmed theorists, what is the nature of the program?  How does it influence the downstream effects we see phenotypically as aging? and so on...

 

My current best guess is gene expression, what most would call an epigenetic mechanism.  The evidence from regenerative animals, negligibly senescent animals and embryology seems to suggest that there are critical changes in gene expression that characterize stages of the lifecycle or the regenerative process.  The two gene expression changes I'm most interested in are the silencing of telomerase and oskm, as well as the various epigenetic "marks" (HDAC, methylation, etc.) that seem to count in some way and act to turn off youthful gene expression.

 

I think the immune system does play a special role in all of this but it still fits.  It's merely the first bodily process to collapse, the ultimate cause of cancer, senescent cell and other junk building up.  Thus the very early start of thymic involution is a great candidate for something that kicks off the process, and it is something that is not caused by damage.  I'm not sure it's been proven as the ultimate cause, but it probably declines because FOXN1 expression gets turned off.

 

One could play the game of asking for earlier and earlier causes.  But that's not how evolution works.  There doesn't have to be an ultimate cause, just an efficient mechanism that solves the problems of survival and reproduction.

 

Another possible mechanism is bioelectricity, specifically the work of Michael Levin at Tufts.  He talks a lot using the programming metaphor for animals that can regenerate limbs and such.   He talks like that because one of the hallmarks of programming is packaging.  In other words, one programming trigger elicits a litany of downstream effects in what are thought to be widely divergent systems.  And this is exactly what happens in regenerative animals.  An acute injury is one trigger.  But from that a cascade involving gene expression, ion channels, proteins, some hormones, pretty much every system in the body are unpackaged and follow a logical subroutine.  They do this consistently every time with perfection.  Levin thinks bioelectricity plays the major role in this, and so do I so I'm offering it as another possible main mechanism that coordinates the program of aging just as much as it seems to in regenerative animal limbs.

 

 

 

Edited by OP2040, 09 December 2018 - 07:30 PM.

[Oakman]

Another possible mechanism is bioelectricity, specifically the work of Michael Levin at Tufts.  He talks a lot using the programming metaphor for animals that can regenerate limbs and such.   He talks like that because one of the hallmarks of programming is packaging.  In other words, one programming trigger elicits a litany of downstream effects in what are thought to be widely divergent systems.  And this is exactly what happens in regenerative animals.  An acute injury is one trigger.  But from that a cascade involving gene expression, ion channels, proteins, some hormones, pretty much every system in the body are unpackaged and follow a logical subroutine.  They do this consistently every time with perfection.  Levin thinks bioelectricity plays the major role in this, and so do I so I'm offering it as another possible main mechanism that coordinates the program of aging just as much as it seems to in regenerative animal limbs.

 

Well, yes, exactly. That was the video I was referring too. Maybe part of the answer about 'Life Force' is contained in that video you referenced in the Bioelectricity thread; I'll put it here again if you don't mind. It's long, but well worth it start to finish!

 

[OP2040]

Thanks Oakman

 

Here's a review paper that directly addresses bioelectricity and aging.  Fascinating stuff.

 

https://www.frontier...2018.00021/full

 

Don't want to turn this into the bioelectricity thread as we already have one of those. 

 

 

[QuestforLife]

 

Life is a force that attempts to control and reverse decay resulting in aging and fights the natural order of the universe - Entropy!

 

 

This is spot on, well done Oakman!

 

Our bodies have evolved mechanisms to resist entropy. These mechanisms fail over time, and it is not yet clear whether this is intentional (clear out the dead wood, i.e. Mitteldorf's view) or simply due to the feedback mechanisms falling out of calibration because they can't catch all the damage (i.e. Aubrey's view). I've read the books of both authors and lean towards Aubrey's argument, although I have some regard for Mitteldorf's view of evolution operating at a group level.

 

What has been shown over the last 20 years is that cells are more than capable of  turning back the clock and becoming young again (or atleast some percentage of them can, which is good enough for our purposes). It only remains to see if we can do this safely in a live organism.

 

The fact that cells are so capable of regeneration makes me think that this does not occur because of a trade-off with cancer. For example, we can't have telomerase active in every cell because this might lead to a rise in cancer rates in those of child bearing age. So our bodies restrict telomerase to prevent this, but this then leads to senescence and (in fact) more cancer, but not until much later in life.

 

If this theory is true, it is good news because it means there is no theoretical reason to stop an old person restoring his cells to youth, providing once this is done the restrictions on proliferation are re-established.

 

Just my view of course, not a statement of fact.