62 replies to this topic

[sub7]

This guy - Andrei Gudkov - sounds so very enthusiastic about this drug being able to eliminate senescent cells and do so much more for anti-aging.
 

 
Now, Entolimod is an experimental drug which will be very had to get a hold of. However he is also claiming that an AIDS drug (which should be fa easier to obtain) works "nicely" for the same purpose. 
 
Please listen and comment. It is, if nothing else, an interesting talk

Edited by caliban, 17 October 2020 - 12:12 PM.
title, intro & tags on request

[smithx]

It appears that this drug actually inhibits apoptosis http://www.cbiolabs....502-biodefense/

 

This would likely have the reverse effect -- keeping senescent cells from dying!

 

 

[Ovidus]

It appears that this drug actually inhibits apoptosis http://www.cbiolabs....502-biodefense/

 

This would likely have the reverse effect -- keeping senescent cells from dying!

 

No, it is not that simple. 
There are various mechanisms at play in aging. The relationship is far far more complictaed.

 

Example: 

You would not want to stop the programmed cell death, right? You actually want to accelerate the process of bad cells dying.

 

But see what happens when you prevent cell death

Hair Repigmentation During Immunotherapy Treatment With an Anti-Programmed Cell Death 1 and Anti-Programmed Cell Death Ligand 1 Agent for Lung Cancer.

 

https://www.ncbi.nlm...pubmed/28700789

[nickthird]

I liked the slides in the presentation.

 

So basically he says we think maybe radiation causes something like accelerated aging, and so we have this drug for radiation (in mice).

Edited by nickthird, 21 August 2019 - 05:04 PM.

[QuestforLife]

Interesting talk, but the AIDS drug and entolimod are not used for the same thing. He is claiming aging needs to be stopped by 1) blocking reverse transcriptases from transposable (virus) elements in genome (using AIDS drugs) and, 2) stimulating innnate immunity (using radiation drug entolimod amongsy others).

 

I find his hypothesis to be totally plausible and worthy of further consideration. Thanks for posting.

 

What I find most interesting is that DNA damage can be 'hidden' and only results in senescence when you force cellular division. Hence putting on weight (form new adipocytes) makes you frail after chemotherapy.

[smithx]

Is there actually any good evidence that endogenous retroviruses are involved in aging?

 

This was my hypothesis back in the 1970s before it was known that there were endogenous retroviruses (or retroviruses actually. They were called "slow viruses" and Kuru was thought to be one -- we now know it was a prion disease).

 

I called them "inactive state viruses" at the time, and most experts told me they couldn't be in the genome (although it was already known that viruses did get into "inactive states", like herpes).

 

My hypothesis was that we're descended from those individuals who were resistant enough to pandemic viruses to survive long enough to reproduce and raise children, but not necessarily more resistant than that, and that the viruses somehow get into our genomes (perhaps by infecting egg and sperm cell progenitors). Our immunity is as long as it needs to be, but eventually the viruses cause enough damage that we see it as "aging".

 

When endogenous retroviruses were discovered I felt somewhat vindicated, but started thinking that we could have evolved to make use of or actually require the products of viral DNA. There was also not a lot of concrete evidence that endogenous retroviruses were expressed until more recently. And since then I haven't followed it closely but didn't see anyone talking about them being a cause of aging. It would be wild if my original hypothesis back in the '70s had any truth to it!

 

 

 

Interesting talk, but the AIDS drug and entolimod are not used for the same thing. He is claiming aging needs to be stopped by 1) blocking reverse transcriptases from transposable (virus) elements in genome (using AIDS drugs) and, 2) stimulating innnate immunity (using radiation drug entolimod amongsy others).

 

I find his hypothesis to be totally plausible and worthy of further consideration. Thanks for posting.

 

What I find most interesting is that DNA damage can be 'hidden' and only results in senescence when you force cellular division. Hence putting on weight (form new adipocytes) makes you frail after chemotherapy.

 

Edited by smithx, 29 August 2019 - 05:33 PM.

[QuestforLife]

Is there any evidence that endogenous retroviruses are involved in aging?

I'd say retroviruses are vital to our existence being involved in rapid cellular division in the embryo for example. So it's likely they infected our single celled ancestors and were eventually co-opted into serving us.

I have a pet theory that they are very important in the evolution of species and explain how species suddenly appear and disappear as well (see: https://www.longecit...ge/#entry875849). Since this mechanism relies on erosion of telomeres in the germline, it makes sense to me that such viruses could be released to rearrange the genome when telomeres become short in normal tissues. This would explain why cancer increases with age and also why immune suppression is so important in controlling bad cells. So yes, I think there is a good argument if not outright evidence retroviruses are involved in aging. It could even be said they we owe our evolution as a species to viruses, but that that using them is like making a deal with the devil, one that entails suffering cancer and aging.

Edited by QuestforLife, 29 August 2019 - 05:28 PM.

[smithx]

Wow I just watched the video and he's basically saying I was right back in 1974 or so when I thought that "inactive state viruses" were the cause of aging.

 

I didn't have the mechanism he's proposing (and we didn't know what retroviruses were), but basically I may have been correct!

 

Too bad I never published anything about it.... *sigh*.

 

 

[smithx]

THIS MAY BE VERY IMPORTANT STUFF!

 

Notes on the presentation:

 

TL/DR: They believe that aging can be stopped and lifespan and healthspan increased by combining reverse transcriptase inhibitors with stimulants of immune response (Entolimod or something similar - he says he has a next gen version which they are going to do clinical trials on)

 

Findings:

• They were trying to create a model of accelerated aging by giving mice a fatal dose of radiation.
• They found that if they give bone marrow transplants after irradiation, the mice survive well although with 25% shorter lifespans
• This is even though they have zero mesenchymal stem cells left
• If they give the mice a high fat diet, which normally would cause growth of at cells, a process which requires working mesenchymal stem cells, the irradiated mice die very quickly
• This is probably also why breast cancer survivors who later change their diet and gain weight become frail
• In non-irradiated mice or other mammals there is an increase in DNA damaged cells with aging similar to that caused by radiation
• They identified the major cause of DNA damage in aging cells to be reverse transcriptases from Line 1 of endogenous retroviruses!
• Reverse transcriptase was only developed once by nature, so it's very similar in HIV, Hepatitis, etc. Therefore anti-retroviral HIV drugs should work against our endogenous reverse transcriptases
• Entolimod extends the lifespan of animals who were irradiated with what should have been fatal doses of radiation
• It also stops normal animals from getting increasing frailty with increasing age
• Combining anti-retroviral drugs with Entolimod or a similar agent they are developing could both increase lifespan and healthspan dramatically

They are doing tests of this on old sled dogs (105 of them) and also plan to do clinical trials in humans.

 

 

 

Edited by smithx, 29 August 2019 - 08:17 PM.

[smithx]

Also see:

 

L1 drives IFN in senescent cells and promotes age-associated inflammation.

https://www.ncbi.nlm...pubmed/30728521

 

LINE-1-encoded reverse Transcriptase as a target in cancer therapy.

https://www.ncbi.nlm...pubmed/29293438

 

Effect of reverse transcriptase inhibitors on LINE-1 and Ty1 reverse transcriptase activities and on LINE-1 retrotransposition

https://www.ncbi.nlm...les/PMC3103432/

TL/DR: Nucleoside-triphosphate reverse transcriptase inhibitors seem to be effective against LINE-1 reverse transcriptase. Others not so  much. ddCTP was by far the most effective. ddCTP is a metabolite of the drug Zalcitabine https://www.drugs.co...alcitabine.html which unfortunately has a bad side-effects profile.

 

Acute and chronic resistance training downregulates select LINE-1 retrotransposon activity markers in human skeletal muscle.

https://www.ncbi.nlm...pubmed/29351416

 

 

Edited by smithx, 29 August 2019 - 08:44 PM.

[QuestforLife]

Wow I just watched the video and he's basically saying I was right back in 1974 or so when I thought that "inactive state viruses" were the cause of aging.

I didn't have the mechanism he's proposing (and we didn't know what retroviruses were), but basically I may have been correct!

Too bad I never published anything about it.... *sigh*.

Ah well. I'll give you credit.

Apparently George Church has removed xenoviruses from Pig DNA so we can use their organs. I wonder if a next gen CRISPR could remove all the transposons from human DNA?

Edited by QuestforLife, 29 August 2019 - 08:42 PM.

[QuestforLife]

They found that if they give bone marrow transplants after irradiation, the mice survive well although with 25% shorter lifespans.
This is even though they have zero mesenchymal stem cells left

If they had to have a bone marrow transplant to avoid death after radiation,then surely this means they must have some mesenchymal stem cells restored? Or are they all used up making new blood and immune cell progenitors? I wish he'd explained this point.

Entolimod extends the lifespan of animals who were irradiated with what should have been fatal doses of radiation.
It also stops normal animals from getting increasing frailty with increasing age

Only in males! This is very strange.

Edited by QuestforLife, 29 August 2019 - 09:19 PM.

[smithx]

Yes it only worked in male mice, which is very odd.

 

More references:

https://www.brown.ed...019-02-06/aging

 

lamivudine  may be the best drug for now

 

 

[QuestforLife]

It is unfortunate that both drugs required for this anti aging treatment are not easily available.

Logically if what you want to do is 1.repress retrotransposons and 2. trigger innate immunity, there should be other ways of doing it.

Just throwing ideas off the top of my head keeping telomeres long will help repress transposons. Also anything that helps with reducing DNA damage would be worth using for example dark roast coffee. And doesn't C60 get macrophages all stirred up? And of course using senolytics takes the pressure off the immune system (we saw in the talk that adding senescent cells to mice actually exhausts the immune system). Finally anti inflammatories are a last line defence in stopping STING getting activated and sterile inflammation getting out of control.

The great thing about this idea is that it ties together so many other theories of aging. You can even understand methylation is overactive with age, as that is better than under activity, which might let transposons escape epigenetic control.

[smithx]

It is unfortunate that both drugs required for this anti aging treatment are not easily available.

 

Not entirely true!

 

Lamivudine is cheap and readily available. I found it for $0.47 per 100mg pill on an Indian website.

 

In the paper I linked (https://www.ncbi.nlm...les/PMC3103432/) 3TC (Lamivudine) was found to be highly suppressive of Line-1 endogenous reverse transcriptase at a 5um concentration.

 

If I am calculating correctly that would give, for someone of fairly average dimensions:

Lamivudine: Molecular weight: 229.26

Desired Concentration: 5 um

 

Total Volume of body fluid estimate: 43.5L
https://www.easycalc.../body-fluid.php

Mass of solute: 49.9mg

(calculator: https://www.physiolo...alculator.html)

Oral route absorption: 82% (https://link.springe...199936010-00004)

Dosage Calculation: 49.9mg * 100/82 = 60.85 = 61mg

 

It is likely that good suppression would be achieved with 50mg, and lower doses probably would produce less side effects. So a conservative(ish) dosage would probably be 50mg 2x/d or one of those 50 cent 100mg tablets cut in half.

 

Note that I AM NOT RECOMMENDING ANYONE DO THIS. Lamivudine has a plethora of potentially serious side effects and some drug and disease interactions which should be thoroughly researched. Anyone who is considering this route should do so under their doctor's care.

Edited by smithx, 30 August 2019 - 03:08 PM.

[smithx]

New technique which might eventually be able to rid us of these endogenous retroviruses: https://www.sciencem...ole-chromosomes

[QuestforLife]

So he skims over the bit in his talk where he claims the reason different species have different levels of DNA damage is due to transposons.

Is there any evidence to substantiate this claim?

Do we need transposons to explain this? For example even the same level of DNA damage (between mice and men say) but with different growth rates would result in many more senescent cells in the faster growing mice (because as we know, growth 'reveals' DNA damage as senescent cells). We know mice also have much higher levels of ROS, so they must have higher DNA damage (unless their antioxidant defences are also much better) as well as a higher grown rate.

Oh and both of these will translate into faster telomere attrition (mice have much longer telomeres then people, but lose them much faster).

So transposons being set loose seems to me to be a consequence of DNA damage, not a cause.

Is there anything to contradict this?

[smithx]

So transposons being set loose seems to me to be a consequence of DNA damage, not a cause.

 

My understanding of the situation is a bit different: What seems to be happening is that endogenous retrovirus L1 reverse transcriptases start inserting stuff (the transposons) here and there in our DNA, causing our cells to not function properly any more. This is a major cause of senescence.

 

One step I'm unclear on is what causes the L1 reverse transcriptases to start being expressed at a certain point in aging. My guess is that it has to do with less ATP being available because we know that DNA repair is inhibited in older individuals (cells) because of lack of energy, and that's one of the bases for NDA+ precursor supplementation.

 

By the way I looked into Entolimod a bit and it's a fairly long polypeptide that's flagellin-derived. In other words, it's derived from the protein that makes up part of the flagella (hairs that produce motion) on bacteria. Lymphocytes sense it using TLR5 because it's an indication of bacterial infection.

 

A Flagellin-Derived Toll-Like Receptor 5 Agonist (Entolimod) Stimulates Cytotoxic Lymphocyte-Mediated Tumor Immunity

https://www.ncbi.nlm...les/PMC3891810/

 

So it's being used to trick the immune system into becoming very active, as if there was a big bacterial infection.

 

I'm not sure if that is the best way to get rid of senescent cells. It might be, but it also might be that Lamivudine (to inhibit the endogenous retrovirus activity) plus something like FOXO4-DRI (to remove the senescent cells) would be even more effective.

 

Edited by smithx, 01 September 2019 - 06:03 PM.

[QuestforLife]

Again you're not really convincing me that transposon are the CAUSE. Yes once they are triggered the more you have in your DNA the worse aging will be (i.e.worse for mice than men), but all I'm seeing at present it that loss of epigenetic control sets them free, and there are plenty of a priori reasons for that.

I agree with your cautious assessment of using entolimod to activate immunity - and it's what I was driving at a few posts back. There are plenty of ways to get the immune system hyped up, and there are other ways of suppressing DNA damage besides anti retroviruses. And of course suppressing reverse transcriptases will stop telomerase working, so might be risky long term (although might this be a good cancer treatment?).

All in all this strikes me as an interesting protocol for someone who is very aged and with few options. As a 40 year old I have much better options at present, at least until I see more data.

[Andey]

  Ive digged a bit and 50 studies later...

Looks like SIRT6 is responsible with repression of retrotransposons in general and LINE1 in particular https://www.nature.c...cles/ncomms6011

 

It also looks like we could use pioglitazone to increase both SIRT1 and SIRT6 https://journals.plo...al.pone.0105456 (not the pioglitazone but same class of drugs)

SIRT6 as all SIRTs is dependant on NAD+, so precursors should give some advantage here and some synergy with PGZ

 

P.S. I was surprised to see that PGZ leaded to better all cause mortality compared to metformin https://www.bmj.com/...c12246264307aa1

[QuestforLife]

Pioglitazone is interesting - it's the equivalent for adipocyte progenitors as Statins are for endothelial progenitors (see my thread) - namely it generates more fat cells. This is useful for diabetics, as it helps control sugar, and a relatively short course of pioglitazone can reduce visceral fat whilst it increases subcutaneous fat. The key finding is that it creates new, small fat cells - rather than swelling up old fat cells.

https://onlinelibrar...38/oby.2009.380

It is risky to stay on it long term however, as there is a small increase in bladder cancer for those on it long term. I wonder if this might be related to exhausting mesenchymal stem cells.

I did not know of its effects on the sirtuins. Possibly NR might be a better bet though, if the sirtuins are you main aim.

[smithx]

Upregulators of SIRT6:

Icariin Intervenes in Cardiac Inflammaging through Upregulation of SIRT6 Enzyme Activity and Inhibition of the NF-Kappa B Pathway
https://www.ncbi.nlm...les/PMC4320867/
(Horny Goat Weed)

Natural polyphenols as sirtuin 6 modulators
https://www.nature.c...598-018-22388-5
"The most potent SIRT6 activator, cyanidin, belonged to anthocyanidins, and produced a 55-fold increase in SIRT6 activity compared to the 3–10 fold increase for the others." - cynadin is a pigment found in many red berries including grapes, bilberry, blackberry, blueberry, cherry, cranberry, elderberry, hawthorn, loganberry, açai berry and raspberry. It can also be found in other fruits such as apples and plums, and in red cabbage and red onion.

Quercetin upregulates it by 10x
 

	
        Compound 	EC 50 value ( µ M) 	Maximal activation (fold)
13 	Luteolin 	270 ± 25 	        6.1
14 	Kaempferol 	n.d 	                3.0
15 	Quercetin 	990 ± 250 	       10
16 	Myricetin 	404 ± 20 	        7.7
17 	Cyanidin 	460 ± 20 	       55
18 	Delphinidin 	760 ± 200 	        6.3 

Possible problems with upregulating SIRT6:

SIRT6 is upregulated and associated with cancer aggressiveness in papillary thyroid cancer via BRAF/ERK/Mcl‑1 pathway
https://www.spandido...m/ijo/50/5/1683

 

SIRT6 promotes the Warburg effect of papillary thyroid cancer cell BCPAP through reactive oxygen species

https://www.dovepres...wed-article-OTT

Sirtuin 6 promotes transforming growth factor-β1/H2O2/HOCl-mediated enhancement of hepatocellular carcinoma cell tumorigenicity by suppressing cellular senescence.

https://www.ncbi.nlm...pubmed/25683165

 

Upregulation of SIRT6 predicts poor prognosis and promotes metastasis of non-small cell lung cancer via the ERK1/2/MMP9 pathway

http://www.oncotarge...50&path[]=30568

 

The role of SIRT6 in tumors

https://pdfs.semanti...818809b3f4d.pdf

(both suppresses and stimulates tumors under some conditions)

 

Edited by smithx, 01 September 2019 - 11:14 PM.

[Andey]

I would be a devils (pioglitazone) advocate for a while)

from https://care.diabete...pplement_2/S155

A large population study in patients with diabetes showed that the incidence of bladder cancer was four to five times lower compared with the incidences of liver, colon, and lung cancer (55). Remarkably, a recently published nationwide case-control study in >600,000 patients with T2DM (56) showed that the use of pioglitazone was associated with a significantly decreased liver cancer incidence (OR 0.83 [95% CI 0.72–0.95]); the protective effect was stronger for higher cumulative dosage and for longer treatment duration. In addition, a decreased risk of colorectal cancer was observed in patients who had used TZDs compared with those who had never used TZDs (adjusted OR 0.86 [95% CI 0.79–0.94]), findings that are consistent with preclinical studies suggesting that peroxisome proliferator–activated receptor γ agonists have antineoplastic effects in colon cancer (57). A study in U.S. veterans showed a 33% reduction in lung cancer risk among TZD users compared with nonusers (adjusted RR 0.67 [95% CI 0.51–0.87]) (58). In accordance with this observation is a recent study from Cleveland reporting an OR of 0.47 (95% CI 0.32–0.68; P < 0.001) in patients for metformin or TZD use (59).

 

TZD is a class pioglitazone`s class of drugs

Bladder cancer is much more prevalent in Caucasian males and it should be a consideration too, other gender-etnicities could feel safer in this regard while taking pioglitazone

 

Polyphenols are certainly an interesting approach, though I am on a fence whether they are safer or just not studied with that level of scrutiny as drugs.

 

Edited by Andey, 02 September 2019 - 06:17 AM.

[QuestforLife]

There have been many studies on pioglitazone, with contradictory conclusions. But I think this most recent one is definitive.

https://www.ncbi.nlm...les/PMC5911601/

That is not to say that it isn't a useful drug, but caution is nonetheless warranted.

[Ovidus]

Thanks a ton for commenting on this.

Absolutely very happy to see you all coming in.

 

Now, please take a look at the other thread I made about this

https://www.longecit...ood-old-line-1/

 

I am trying to explain in the thread above how this all ties in so well with what David Sinclair is saying. To me this all can be summed up as follows:
 

Line-1 is nothing but trouble. It helps us not at all (at least on an individual level; may have helped the species)
Its expression is kept under control through SIRT6. When we get old, for reasons I kind of understand but cannot elaborate on since I am not confident of my grasp thereof, SIRT6 gets inefficient in suppressing Line-1

 

Line-1 then gets out of control and aging as well as cancer ensue.

 

 

1- QuestforLife, can you please explain how Line-1 helps the rapid cell division at the embryo stage? 
 

2- I thought it was simply the inability of SIRT6 to suppress Line-1 that marks the tipping point in the system. You guys spoke extensively of telomeres, however. Can you please explain how telomeres play a role here? Is is that shorter telomeres --> loss of SIRT 6 function?

 

3- Of course we want to think of as many angles of attack as possible, but why not focus on the specific drug that has been proposed and also studied for reducing the activity of Line-1 retrotransposition? i.e. Lamivudine 

check this out

https://sci-hub.tw/h...met.2019.02.014

 

Yes, Lamivudine does have side effects, but when treating AIDS patients with this drug (it is an HIV medicine), they target the reduction of HIV load to undetectable levels. We do not need such aggressive suppression of reverse transcription activity. Can we not use a low-ish dose for an extended period?
I do not want to trivialize this drug, but when I read the side effects, most seem not so terrible (I am emphasizing "most")

 

thanks again

[smithx]

Ovidus: Lamivudine does inhibit LINE1 reverse transcriptase, but SIRT6 prevents LINE1 from making the reverse transcriptase in the first place.

 

So it seems that a multi-pronged approach could be better:

 

• stimulate SIRT6 (perhaps via polyphenols) to prevent LINE1 reverse transcriptase from being expressed as much as possible
• take a reverse transcripase inhibitor (the best one for the purpose currently being Lamivudine) to inactivate whatever does get expressed

 

With regard to telomeres, SIRT6 has an affinity for them and seems to be protective. So another reason to stimulate SIRT6.

 

By the way Lamivudine is a first line drug for Hep B, which seems to be its primary use.

 

I did a dosage calculation of Lamivudine above, but cyanidin dosing still seems a bit uncertain. In the paper I cited (https://www.nature.c...598-018-22388-5), cyanidin has a 55 fold stimulatory effect on SIRT6, however the concentration cited is 460 um +- 20um.

 

This would translate, for a man of fairly average size who has about 44L of fluid in his body to a dose of about 5.5g. It's unclear whether a 55x stimulation is really necessary, or whether there's a threshold effect below some molarity.

 

In the meantime I have started taking blackcurrant standardized extract from Jarrow, 400mg twice a day, in the hope that it will stimulate SIRT6 to some useful extent. This is probably only about 60mg of cyanidin, however.

 

See also: https://www.ncbi.nlm...pubmed/21121259

 

 

 

 

 

 

Edited by smithx, 03 September 2019 - 02:30 AM.

[Ovidus]

In the other thread I asked the following, what do you all think?

 

The big question is this: 
Can we just completely SUPPRESS ALL REVERSE TRANSCRIPTASE ACTIVITY? Do we need some reverse transcriptase?

 

Only useful function of reverse transcriptase is when telomerase is active and it lengthens telomeres by inserting copies of telomere sequences into the genome through the use of Reverse Transcriptase. However, adults do not express any telomerase anyways. 

In fact, telomerase gets expressed in adult humans mostly during cancer (AFAIK, something like 90% of cancers need telomerase to function).
So could it be that we can whack both cancer and aging over the head by inhibiting reverse transcriptase?

 

[Andey]

Are there any studies on Lamivudine when used as a monotherapy safety longterm?

 

There are definitely some as a part of ART anti HIV therapy but in general all cause mortality is significantly higher on ART then in healthy controls. I believe its unknown why and probably Lamivudine is not a bad actor here compared to other drugs in ART.

When used in anti HB therapy I beleive it doesnt get used for long for one individual as virus gains resistance to it with time.

 

[QuestforLife]

Line-1 then gets out of control and aging as well as cancer ensue.


1- QuestforLife, can you please explain how Line-1 helps the rapid cell division at the embryo stage?

2- I thought it was simply the inability of SIRT6 to suppress Line-1 that marks the tipping point in the system. You guys spoke extensively of telomeres, however. Can you please explain how telomeres play a role here? Is is that shorter telomeres --> loss of SIRT 6 function?

To whoever asked - yes (I also suggested this upthread), LINE-1 inhibition might inhibit cancer, or at least the rapid mutations caused by genome rearrangement. It wouldn't stop the chromosomal fusions and breaks however, or the LINE-1 near the breaks that are set free, as these breaks are caused when telomeres are eroded to the point where they can no longer inhibit the DNA damage response. Hence why maintaining telomeres is a defence against LINE-1 (at an earlier stage).

I assume SIRT6 is useful in keeping DNA rolled up around chromatin and suppresses LINE-1 this way.

Here is an article where they talk about how LINE-1 is required at the embryo stage, and how it helps maintain pluripotency. This makes sense when you think that embryonic (and induced pluripotent) stem cells are the only ones that have sufficient telomerase to be immortal and also how some flies ( drosophila) actually don't have telomerase - they use the repetitive elements of transposons in the same way. I should say that not all scientists agree with this article (yet):

https://www.sciencem...-it-past-embryo

[Andey]

From this study https://www.hindawi....l/2019/2818415/ in Fig 3 looks like various retrotranposons expressed differently in different tissues at different time, expression of some fall during aging. One could argue that some of them could have some function and suppressing all of them would lead to some lost.

https://www.hindawi....9/2818415/fig3/

That said looking at this graph LINEs are going only up with age.

 

In this context activating SIRT6, only to suppress what is supposed in the cell program to suppress, looks like a more prudent approach.