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Old human cells rejuvenated in breakthrough discovery on ageing

senescent cells rejuvenation

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#181 Rocket

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Posted 21 March 2018 - 01:06 AM

Most people can tell if a person is in their late 30's or early 40's, the question is, why? Things begin to decline around this time, why? Grey hair, wrinkles, athletes even retire around this age. If there aren't enough senescent cells at this point to matter, then a buildup of senescent cells or SASP is not really as big of an aging factor as we thought, at least not at this point. It may still be more related to Advanced Glycation Endproducts, glucosepane mostly but also pentosidine and fructosamine.

Its the extracellular matrix that gives away age in 30s and 40s. Wrinkles like crows feet are NOT senescent cells.

Athletes retire around 35 because connective tissue fails.... Shoulders and knees and spinal discs. That's not senescent cells! That is wear and tear on tissues that don't repair like themselves like a skin bruise.

Also the loss of hgh takes its toll on not repairing the body like when younger. That is NOT senescent cells Nate.

Senescent cells contribute VERY VERY VERY little to 35 and 40 year old people.


Senescent cells have been hyped up to be the bogey man on this site. True in old age they accumulate enough to be a large part of aging, but hardly the major 70% factor of aging that people want them to be.

30 year olds should not be taking FOXO4. 40 sure. 50 definitely.

Senescent cells are not the difference between 25 and 35!!!!!

Loss of hgh, connective tissue degradation, extracellular matrix damage, mitochondrial changes, gene expression... Loss of muscle, thinning skin. Things like v02 max and cardiovascular health are secondary aging that can be controlled through exercise and diet.

People are going to be let down by FOXO4 if they think they are going to look younger or become younger.... Your shoulders and discs and tendons won't rejuvenate. Your vascular system won't decalcify. Your brain won't turn 22 again. If you're old enough some biomarkers may improve like egfr, which is important but.......

Edited by Rocket, 21 March 2018 - 01:14 AM.

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#182 Nate-2004

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Posted 21 March 2018 - 01:23 AM

I agree, and I'm guessing by and large that's glucosepane? As someone in his 40's I'm more interested in rejuvenation therapies that involve repairing the ECM.


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#183 Rocket

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Posted 21 March 2018 - 01:41 AM

I agree, and I'm guessing by and large that's glucosepane? As someone in his 40's I'm more interested in rejuvenation therapies that involve repairing the ECM.

Its not even ages at 35 and 40 making you look older. Thinning skin. Loss of fat. Sun damage. Stress. Wear and tear from youth and partying and abusing your body. And yes, mitochodrial loss of function and gene expression.

If you want to improve your external ECM the you should try dermarolling.

At this time there is nothing you can do for the internal ECM and restoring strength to connective tissue. Anabolics like nandrolne are known to increase collages production in connective tissue... So you can try that. I know its definitely helped me with a shoulder injury to continue weight training with heavy weights. But its illegal and you need to take a host of supportive chemicals to maintain health since it affects lipids and the liver and can lead to gyno ... But it works,

Edited by Rocket, 21 March 2018 - 01:48 AM.


#184 Nate-2004

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Posted 21 March 2018 - 01:55 AM

I've stayed out of the sun most of my life, though I did go through a short phase of trying to tan in my 20's but it was a 6 month thing, for the most part I've avoided sun for this reason, still, not enough to slow that damage. Why do we lose subcutaneous fat? Why do we lose skin elasticity? Why does it thin? What are the root causes here? I'm specifically talking about ages 25 to 45. Aside from photodamage, which for me is rare, what else is there?

 

We know how to target mitochondrial dysfunction issues but I'm guessing it's all mostly advanced glycation end products, otherwise what else is there?

 

I can tell you, there is nothing out there yet that can break the crosslinks that cause this yet.


Edited by Nate-2004, 21 March 2018 - 02:04 AM.

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#185 QuestforLife

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Posted 21 March 2018 - 10:44 AM

Skin turns over every month (roughly). As telomeres shorten they turnover less often. So you have a given cell for longer.  In older cells' metabolism and autophagy is reduced so proteins hang around for longer and are more likely to be damaged by ROS or bonded to glucose. That is probably all there is to it in middle age.

 

But there are lots of complicated downstream consequences. The stratum corneum starts to let moisture though so your skin gets drier. I'm not sure why subcutaneous fat is lost so early in life - but I have been working on replacing mine with glitazone treatment (stimulates adipocyte differentiation). It seems to be working.

 

Dermarolling also works because it forces the skin cells to replace more regularly. From this we can gather that the body is very conservative and always holds back considerable replenishment capacity. 

 

I wouldn't stress yourself over glucosepane - I've never seen any evidence that this is a big deal at age 40. It builds up slowly and forms a minority of the sugary crosslinks you have at any given time (even if it is the most persistent component). We'll get a glucosepane breaker by the time we really need it (yes I donate to SENS).


Edited by QuestforLife, 21 March 2018 - 10:51 AM.


#186 Nate-2004

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Posted 21 March 2018 - 12:02 PM

Skin turns over every month (roughly). As telomeres shorten they turnover less often. So you have a given cell for longer.  In older cells' metabolism and autophagy is reduced so proteins hang around for longer and are more likely to be damaged by ROS or bonded to glucose. That is probably all there is to it in middle age.

 

But there are lots of complicated downstream consequences. The stratum corneum starts to let moisture though so your skin gets drier. I'm not sure why subcutaneous fat is lost so early in life - but I have been working on replacing mine with glitazone treatment (stimulates adipocyte differentiation). It seems to be working.

 

Dermarolling also works because it forces the skin cells to replace more regularly. From this we can gather that the body is very conservative and always holds back considerable replenishment capacity. 

 

I wouldn't stress yourself over glucosepane - I've never seen any evidence that this is a big deal at age 40. It builds up slowly and forms a minority of the sugary crosslinks you have at any given time (even if it is the most persistent component). We'll get a glucosepane breaker by the time we really need it (yes I donate to SENS).

 

I've never seen any convincing before / after photos of dermarolling. 

 

Interesting take though. So we're back to telomeres and ROS on this. I haven't heard of glitazone, I tried voluplus but it did literally nothing.

 

I looked up glitazones and apparently it adds new fat and reduces insulin resistance. Is it topical or oral or injected? Where are you getting this?


Edited by Nate-2004, 21 March 2018 - 12:06 PM.

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#187 Rocket

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Posted 22 March 2018 - 01:16 AM

Skin turns over every month (roughly). As telomeres shorten they turnover less often. So you have a given cell for longer. In older cells' metabolism and autophagy is reduced so proteins hang around for longer and are more likely to be damaged by ROS or bonded to glucose. That is probably all there is to it in middle age.

But there are lots of complicated downstream consequences. The stratum corneum starts to let moisture though so your skin gets drier. I'm not sure why subcutaneous fat is lost so early in life - but I have been working on replacing mine with glitazone treatment (stimulates adipocyte differentiation). It seems to be working.

Dermarolling also works because it forces the skin cells to replace more regularly. From this we can gather that the body is very conservative and always holds back considerable replenishment capacity.

I wouldn't stress yourself over glucosepane - I've never seen any evidence that this is a big deal at age 40. It builds up slowly and forms a minority of the sugary crosslinks you have at any given time (even if it is the most persistent component). We'll get a glucosepane breaker by the time we really need it (yes I donate to SENS).


Totally agree with you over AGES and 40.

Also you're right about the body holding back on tremendous replenishment capacity. I broke my second metatarsal on January 9. 6weeks later I was back in the gym doing squats. I even quit wearing the plastic boot over 2 weeks early and did everything I wasn't supposed to do like walk barefoot at home. I am approaching mid 40s and thought i was in for months of pain and limping. Nope. Healed up like a youngster and totally pain free, knock on wood. Even the doctor warned me I was in for months of pain ahead of me. Nope.

I do take 15g of vitamin c for cardiovascular so maybe it helped bone heal through the same pathway it prevents damage to arteries... Idk.

But back to senescent cells, sort of like AGES I doubt there is very much affect on the body until mid 40s. I just don't understand why the young guys in their 30s are bothering to damage their body to eliminate NO harmful senescent cells that their immune system was going to eliminate anyway. Every medicine contains poison afterall.

And back to Nate, dermarolling is sworn to by many people. So is that blood plasma platelet therapy that Kim Kardashian uses. The science behind it seems valid.

Edited by Rocket, 22 March 2018 - 01:33 AM.

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#188 QuestforLife

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Posted 22 March 2018 - 12:09 PM

Nate - I bought pioglitazone from Aipctshop in tablet form. For more info please read 2010 paper 'Pioglitazone Increases the Proportion of Small Cells in Human Abdominal Subcutaneous Adipose Tissue.' I did it for 6 rather than the full 12 weeks of the study. I wouldn't recommend anyone else trying this however, without being very well informed and read up on the small but real increase in the chance of bladder cancer.

 

Rocket - ditto, I tore a ligament in my finger and was told 8 weeks in a splint, then 3-4 months of physio with no weights or Judo in that time. I was out of the splint in 4 weeks and back to Judo at 6 weeks. What to Doctors know, eh? :-D


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#189 Nate-2004

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Posted 22 March 2018 - 12:58 PM

Thanks for the info guys. I'll look into this. I think this is highly relevant because the message by and large lately is that senescent cells are a major root cause of aging, yet if people who are showing the early signs of age in their 30's and 40's, the signs you described above, do not have a number of senescent cells that would have much of an effect in terms of SASP, then we're looking at another phase of aging that doesn't include the main targets. I'm still not so sure the root cause of this decline in subcutaneous fat, collagen, hyaluronic acid, elastin, bone density, increased stiffness in joints and muscles, a drop in growth hormone and other biomarkers doesn't have a root cause. I'm not so sure what, if not AGEs, are at the root of this decline. What specifically is signaling cells to turn over less and become more conservative?

 

It appears I've been wasting time somewhat on trying to eliminate or as far as this thread that I started, revive senescent cells.

 

BTW any recommendations on a dermaroller? How many mm? 1mm? Maybe I'll take these questions to another thread.

 

Who is marking all my posts as dangerous and irresponsible lately? I hate these features, they just give trolls something to annoy people with.


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#190 pamojja

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Posted 22 March 2018 - 01:09 PM

 

Who is marking all my posts as dangerous and irresponsible lately? I hate these features, they just give trolls something to annoy people with.

 

It more and more reminds me of the Orwellian Chinese Social Credit System. I mean I understand that misjudgments can be made, by assuming such would encourage more quality contributions. But de facto and for a couple of years has scared away most quality contributors, and made a feast of mobbing trolls out of this forum.


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#191 QuestforLife

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Posted 22 March 2018 - 02:25 PM

Hi Nate

 

This is my opinion, albeit one based on reading hundreds of papers over the years (if not thousands), but the early phases of aging are likely caused by the slowing down phase of (mitotic) cells rather than their senescence. Going back to the paper that started this thread - I still think this intervention is valid (if it can be made to work in vivo), because there are many cells that are approaching senescence all the time (before arrest, apoptosis or immune clearance and replacement), and if we could rejuvenate these that would effectively be a genuine reversal of aging, because you would not be relying (as so many interventions do) on faster replacement from what is a finite stem cell pool, but would be getting a free lunch (younger cells) for nothing.

 

Incidentally I originally criticized the paper in question for not proving that the cells they had rejuvenated in vitro were genuinely senescent, but this is irrelevant for our purposes as near senescent or senescent rejuvenation is still useful in vivo. This is not senescent cell clearance, it is putting such cells back to work.

 

Regarding my plan to use pterostilbene instead of resveratrol, I've had incredible difficulty getting pterostilbene powder in the UK and several cancelled orders later and I've finally got a bag of tablets that I'm emptying out myself. I took 1g (of actual pterostilbene, total weight is more like 6g) last night and another 1 g this morning in a fruit juice. Have had no stomach upsets so far. I intend to continue this for another 1 day (48 hours total) and will report back any results.

 

I don't know who is marking down your posts Nate, I've up-rated a few of them to balance things out!

 

 


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#192 Nate-2004

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Posted 22 March 2018 - 06:26 PM

I wonder how we can reverse the slowing down. If by that you mean cell turnover, then early aging is something that's not as prioritized or looked at in terms of rejuvenation research. It would be great to see more followup on this resveratrol study though because maybe that's the key, but maybe not. What would happen if we sped these things back up? Would that be a short term gain with long term negative consequences if other things aren't dealt with?

 

Yeah without knowing if pterostilbene is the same you're shooting in the dark. Apigenin is something you'll want to take with resveratrol, since resveratrol improves the bioavailability (cmax) of apigenin I assume that apigenin might also improve the bioavailability of resveratrol, since it's a competition thing. I noticed that while apigenin helps me sleep better, if I take it with resv, it keeps me awake. All speculation based on a study I linked in the Manipulating Mitochondrial Dynamics thread and elsewhere.

 

Thanks for the vote ups, but just so you know, the green ones are the only one that counts, the middle ones are neutral. It's a weird system.


Edited by Nate-2004, 22 March 2018 - 06:26 PM.

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#193 QuestforLife

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Posted 23 March 2018 - 08:58 PM

Well that's a good question Nate and what people have been debating about telomerase treatment since the late 90s; undoubtedly it rejuvenates (speeds up) cells, but does it encourage cancers? Based on my understanding, the answer is no, but others disagree. A similar thing could be said for this resveratrol treatment; is it a good idea to put old cells back to work? Again, my reading is the situation is that extending telomeres is sufficient to make an old cell good again, others may disagree. But I take some heart that resveratrol is known to be strongly anti cancer and I think very short telomeres are a cause of cancer.

I've completed my pterostilbene dosing. I took 6grams over 72 hours in the end. Based on the paper I think it's the backbone common to all the resveratrol analogues, resveratrol itself, and indeed pterostilbene that is the magic ingredient that permits telomere elongation in old cells. But I have doubts someone of my age (39) has sufficient old cells to benefit from this treatment. Still, I see this as a sensible preventative treatment.
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