Sight restored by turning back the epigenetic clock

https://www.nature.com/articles/d41586-020-03119-1

by evo_9 • 6 years ago

310 101 6 years ago

nature.com

jy14898• 6 years ago

in mice

olliej• 6 years ago

Right? Can we get the title updated?

Metacelsus2• 6 years ago

I previously posted this: https://www.nature.com/articles/s41586-020-2975-4

Maybe because I included (in mice) in the title, it didn't get upvoted as much as this post.

andy_ppp3• 6 years ago

I’m really starting to hate this trope, I think everyone should just assume “in mice” unless the title states “in humans” as that is a much rarer event for research papers to be at that stage than mice or other mammals.

hyperdunc• 6 years ago

People will assume what they will. I'd prefer a more explicit title.

joe_the_user• 6 years ago

I'd like to see what happens if all the youth renewal strategies done on laboratory mice are applied to older, wild-caught mice of whatever variety is closest to lab mice.

I've heard the claim when calorie limiting applied to wild mice, they ... just die - they already have limited calories.

But just that leap might be a decent lesson.

Turing_Machine• 6 years ago

"In mice" isn't the whole story here.

"The authors found that OSK expression enhanced axon regrowth and cell survival in human neurons in vitro."

Granted, that's not actually restoring sight to an in vivo human patient just yet, but neither is it "in mice".

david-gpu• 6 years ago

David Sinclair talks about this work in his book Lifespan, in case you are interested in the current state of anti-aging treatments.

It's very exciting that we are beginning to unravel a general mechanism that drives aging across species.

011000112• 6 years ago

In other news, they're also close to releasing eyedrops to help with presbyopia: https://modernod.com/articles/2020-sept/coming-soon-presbyop...

UNR844-Cl claims to restore flexibility to the aging lens by breaking the disulfide bonds that form between proteins in the lens. It's a really simple molecule too, composed of common supplements(lipoic acid and choline), so it looks like the risk is fairly low.

hourislate• 6 years ago

I was just listening to some techniques on YouTube on how to fix presbyopia by switching to older prescriptions from current prescriptions to bring back the elasticity. Apparently focusing on reading or a computer screen too much can create the lens from returning to it's original condition/state as it remains locked/seized up. Might be bullshit but these eye drops would be amazing. I wonder if this is what David Sinclair was talking about when he said they will be able to fix bad vision soon.

troughway• 6 years ago

Is this Active Focus?

Tade0• 6 years ago

I've been following this drug's development process since back when it was named EV06.

Currently people with presbyopia who get laser eye surgery have one eye corrected for looking at nearby objects and the other for those which are far away - this works, but is not ideal.

With UNR844 one could potentially have the same typeof correction in both eyes.

fnord77• 6 years ago

I've been watching this one for a while. If it works out, it will be fantastic (well, not for optometrists)

DennisP• 6 years ago

I was confused at first because your link is about a different approach, using drugs that temporarily constrict the pupil. The drug that fixes the lens is in human trials too, and would also just be an eye drop. Here's an article:

https://www.healio.com/news/optometry/20201012/further-study...

011000112• 6 years ago

The link mentions both approaches. The lens constricting drugs are listed first.

reasonattlm• 6 years ago

Several research groups and companies are working on in vivo applications of cellular reprogramming. Since its discovery, reprogramming has been used to produce induced pluripotent stem cells from any other type of cell. That process has been found to reverse age-related changes in epigenetic patterns and mitochondrial function characteristic of cells in old tissues.

Introducing the factors capable of reprogramming cells into a living animal may produce effects akin to stem cell therapy by converting a small number of cells into induced pluripotent stem cells, followed by stem cell signaling that beneficially affects tissue health more broadly. Alternatively, many cells may have their epigenetic markers reset to a more youthful state without losing their identity to become induced pluripotent stem cells. Or both. Beyond this, there is certainly the threat of cancer or structural damage to tissue through the conversion of too many cells, and this class of therapy will require careful development to ensure safety, even as the mouse data continues to look quite interesting.

David Sinclair has been pushing an epigenetic-centric view of aging of late, with analogies to information systems and computing. The most interesting part of the the supporting work suggests that DNA repair of double strand breaks has the side-effect of driving alteration of the epigenome in characteristic ways with age. That will be an important connection between stochastic nuclear DNA damage and deterministic global effects throughout the body, should the evidence continue to hold up.

As this illustrates, however, epigenetic change is a downstream issue in aging, a reaction to events and a changing environment, not a first cause. Fixing it may or may not turn out to be particularly useful in the broader picture of aging, depending on exactly where it sits in the web of cause and consequence. As a comparable example, hypertension is a major downstream issue in aging. It is far removed from root causes such as cross-link formation and inflammation, but is also a proximate cause of many forms of further dysfunction, such as pressure damage to delicate tissues in the brain. Controlling hypertension without addressing its causes is both possible and beneficial - but the benefits are limited by the fact that those root causes are still there, chewing away at the body in a thousand other ways.

treeman7910• 6 years ago

Lost much of my vision. Was restored by blood thinners and Diamox.

Not what the drugs were intended to treat. But a surprisingly effect.

2 dozen doctors had not been able to help me.

crispyporkbites• 6 years ago

You saw 25 doctors?

casion• 6 years ago

Doesn't seem particularly weird to me, I've seen more than that myself for an issue.

scsilver• 6 years ago

He only saw the last doctor.

treeman7910• 6 years ago

Probably about 15. Most multiple times.

Now I may have had less problems if I had taken the baby aspirin like I was supposed to. As that is a mild blood thinner.

joshuaissac• 6 years ago

What made you consider those drugs for your eyesight?

treeman7910• 6 years ago

Didn’t consider drugs for vision. Spent like 20k on glasses and eye doctors to little success.

Have increased cranial pressure. Makes eyes want go double. 5th or sixth nerve gets weak.

Diamox lowers pressure. Nerves work better, double vision goes away. Prism glasses help if I’m having a bad time.

Other issue was black disc / hallucinations in vision.

Doctors found I had a genetic clotting disorder. Only found due to clots showing up elsewhere in body.

Blood thinners are standard treatment. Aside from double vision all my eye Problems went away in a few days. So basically eye mini strokes.

Everything comes back whenever I try and go off meds.

radicaldreamer• 6 years ago

Any hints to the mechanism of action for your case? How old are you btw, if you don't mind sharing?

treeman7910• 6 years ago

40.

playcache• 6 years ago

I would love something like this. Over the past 5 years I have experienced my eyesight degrade since reaching 40 years old. I always use to quietly brag to myself about having such good vision. And then suddenly it gets a little bit of challenge to read, so you get a weak strain of reading glasses and from their you continue up in strengh ratings until you realise the person over the road from you has a blurred face and you have gone from needing reading glasses to needing glasses all of the time.

annoyingnoob• 6 years ago

Same experience, aging sucks.

thelittleone• 6 years ago

Precisely same here most noticeable on screens and in morning. My wife passed me her glasses and my screen became sharper than ever. My fear is using them too much might then mess up my non glasses vision.

mlyle4• 6 years ago

Probably not. Age-related near vision loss is due to the lens of your eye losing flexibility with age, and not being able to change shape as much to focus on near things, and not any kind of baseline refractive error.

rufus_foreman• 6 years ago

Hopefully your optometrist has warned you that it just gets worse and there's nothing they can do.

fpgaminer4• 6 years ago

Since we're commiserating: the vergence of my eyes is failing and I'm not even 40. My actual vision is perfect; better than ever. But apparently my eyes don't converge so well anymore, giving me horrific headaches if I look at any kind of screen for more than a few minutes :( Really sucks. Doc gave me prism lens so I can use a computer again, but they're exhausting to use. Hoping I can find a specialist after the pandemic is over and figure out a better option; really don't want this to get worse.

Kind of sick joke, considering I spent almost a decade of my career doing computational imaging and computer vision work.

2020 :/

justinclift2• 6 years ago

Wonder if a VR headset with a custom interpupillary distance (IPD) would work for you? eg set it to a distance that's not physically correct, but er... more correct for how your eyes operate.

If it's works, you'd be able to read text again. You'd just need to do it from inside VR. ;)

treeman7910• 6 years ago

Look into IIH, 5th or sixth nerve is affected, causes double vision.

Diamox fixes my double vision. Before that I was using prism glasses.

ArnoVW• 6 years ago

Contact this guy. It looks like a non-surgical solution may be possible :

  https://media.ccc.de/v/35c3-9370-hacking_how_we_see

Essentially, they use a VR headset to offset the shifted vision, and then gradually correct the difference in therapeutic sessions. Pretty ingenious.

tartoran2• 6 years ago

I had something like that and doing a few minutes a day of magic eye / 3d stereograms sessions helped me a lot. That consisted of learninng how to see them then learning to hold the image up in 3D (feels like starring behind the image) then rotating the eyes around while holding the stereogram in focus (looking at all parts of the image not just center). This helped strenghten my eye muscles and tension/headaches went away.

flippinburgers• 6 years ago

Vision loss + tinnitus: something that makes getting up in the morning hard to do!

The thrill of being able to restore these two things alone would be indescribable.

mlyle4• 6 years ago

Cellular clocks may not be so useful with this.

Your eye has "extra flexibility" to focus at birth (that is, it can focus beyond infinity and nearer than is useful), but it slowly hardens and becomes less flexible. Around age 40-50 is when you really start to notice the loss in range, assuming you had something close to a normal balance between distance and near vision to begin with.

xwdv3• 6 years ago

Any way to maintain flexibility through diet and exercise?

inglor_cz4• 6 years ago

Anecdote with N == 1 as usual.

I am 42 and I started experimenting with NMN, NR and resveratrol in January.

My eyesight measurably improved, by about 1,25 dp, within weeks (I am shortsighted since childhood.) I no longer notice any eye strain even after looking into screens for hours. My very, very mild presbyopia disappeared. Also, I believe that I can see colors much more brightly, but this is something that cannot be measured easily, if at all.

RcouF1uZ4gsC• 6 years ago

They infected RGCs in mice with adeno-associated viruses.

In Mice

https://mobile.twitter.com/justsaysinmice

bitwize• 6 years ago

In mice.

kgin• 6 years ago

The eye was selected as the area for this research because it is self-contained in multiple ways. Viruses used to insert the OSK genes in they eye will stay in the eye, so there is less concern about possible effects elsewhere in the body. That provides an easier path towards translating and getting regulatory approval in humans.

But the very cool thing is there is no reason to believe that this technique couldn't eventually be used throughout the whole body.

yread• 6 years ago

This stuff could be BIG deal. Currently, most of therapies involve taking the cells out to reprogram them back to ipsc and trying to stuff them back again. IF this is viable in humans - adenoviruses work for us, too - or nanolipid vesicles. So, it should. Source: wife epigenetics postdoc in ipsc therapy

daemonk• 6 years ago

I think one of the guys who founded Moderna originally wanted to inject mRNA to induce pluripotent stem cells. It would be great if that can somehow work for this. Instead of using an adenovirus to insert the genes, we can inject mRNA to induce expression of the transcription factors long enough for it to take effect.

mensetmanusman• 6 years ago

Look how large a collaboration effort:

Affiliations Department of Genetics, Blavatnik Institute, Paul F. Glenn Center for Biology of Aging Research, Harvard Medical School, Boston, MA, USA Yuancheng Lu, Xiao Tian, Daniel L. Vera, Qiurui Zeng, Doudou Yu, Michael S. Bonkowski, Jae-Hyun Yang, Michael B. Schultz, Alice E. Kane, Karolina Chwalek, Luis A. Rajman & David A. Sinclair

Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USA Benedikt Brommer, Chen Wang, Songlin Zhou & Zhigang He

Department of Ophthalmology, Harvard Medical School, Boston, MA, USA Benedikt Brommer, Anitha Krishnan, Chen Wang, Songlin Zhou, Emma M. Hoffmann, Margarete M. Karg, Ekaterina Korobkina, Meredith S. Gregory-Ksander, Bruce R. Ksander & Zhigang He

Schepens Eye Research Institute of Mass Eye and Ear, Harvard Medical School, Boston, MA, USA Anitha Krishnan, Emma M. Hoffmann, Margarete M. Karg, Ekaterina Korobkina, Meredith S. Gregory-Ksander & Bruce R. Ksander

Division of Genetics, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA Margarita Meer & Vadim N. Gladyshev

Department of Pathology, Yale School of Medicine, New Haven, CT, USA Margarita Meer & Morgan E. Levine

Department of Genetics, Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA Noah Davidsohn & George M. Church

Department of Molecular Biology, Cancer Center and Center for Regenerative Medicine, Massachusetts General Hospital, Boston, MA, USA Konrad Hochedlinger

Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA Steve Horvath

Laboratory for Ageing Research, Department of Pharmacology, School of Medical Sciences, The University of New South Wales, Sydney, New South Wales, Australia David A. Sinclair

Metacelsus2• 6 years ago

I previously posted this: https://www.nature.com/articles/s41586-020-2975-4

Maybe because I included (in mice) in the title, it didn't get upvoted as much as this post.

justinclift2• 6 years ago

Looking at both, your link seems to go to a much less readable version of the article?

pkaye• 6 years ago

There is also some drugs being tested for some types of tinnitus and hearing loss. One of them is FX-322 by Frequency Therapeutics.

https://www.biospace.com/article/releases/frequency-therapeu...

iandanforth• 6 years ago

IN MICE.

luckman212• 6 years ago

I am not trying to diminish the work being reported on here. I just want to comment that I see these kinds of articles posted frequently, and they always leave me feeling like

Experimental "foo" results in NN% improvement in "quux" in new study. Possible human trials scheduled for "someday far far away" and could "one day" lead to rainbow colored pet unicorns for all humans.

Basically, some amazing thing may happen someday and I'll never hear about it and will likely be dead and gone well before it bears fruit.

It would be wonderful if there was a site that summarized these kinds of breakthrough research projects in a way that was practical for laypeople. E.g. disease, research being done, possible treatment/cure, stage of testing, availability to general public / how to get it or become part of trial group, cost, risks etc. E.g. I'd love to be able to star & watch this like a Github repo and be notified of progress...

xiphias2• 6 years ago

There is, it’s called lifespan.io

https://www.lifespan.io/road-maps/the-rejuvenation-roadmap/

rubicon334• 6 years ago

I assume that foundation was started by David A. Sinclair? Same author of this book?

https://www.amazon.com/Lifespan-audiobook/dp/B07QGH1Q43/ref=...

Very interesting research in that book but honestly, very little actionable paths for the reader. We aren't yet to a point where it's possible to just pop a pill and live another 100 years. Probably the most effective thing you can do right now is caloric restriction, but that can kind of suck. The holy grail would be some way to eat normally, and slow the aging process.

jradd• 6 years ago

is this why big–pharma harvest blue bloods? i'm not sure i believe this hoopla about the tree of life.

but i'm interested in the biomedical applications from obscure species that feature bioluminescence, magic pheromones and how to test the quality of Eel I just put on back order.

i loved your italicized block. don't down vote this one.

dehrmann• 6 years ago

Sounds like battery research.

WoodenChair• 6 years ago

I feel this way too, but I often find those circulating articles are in mainstream media by people who don't understand what they're reporting on or in "science will cure everything" blogs. However, this is a summary posted on one of the most respected journals in the world's website. The article/study it is summarizing was peer reviewed and developed by scientists at some of the world's top institutions. Sure, we shouldn't get caught up in reputation as a marker of quality, but at the same time it does count for something... this is not the same as most of the breathless articles that I see circulate on social media.

saurik• 6 years ago

I didn't feel like the comment was arguing about the quality of the articles, but more the notion of how reading an article about some point in time progress of some early thing feels useless: what you want is to follow the thing. It is like if you hear about some new piece of software when it is just some proof of concept and it won't be a "real thing" for three years but you want to follow it so you can keep learning about it and watch its progress... so you watch its git repository or subscribe to its mailing list or whatever, and you can do that; but with science, the process--which at the milestones of publishing feels very open--is usually some weird closed competitive process.

elric3• 6 years ago

I agree with the sentiment, but I don't think it's actually as gloomy as that. Those kinds of articles help keep science in the news, which in turn keeps people interested in science, which hopefully leads to people considering careers in science.

Maybe these things bear fruit, maybe they don't, but at least now we know about them, and maybe it'll inspire someone somewhere.

probably_wrong• 6 years ago

I have a relative that went blind due to double corneal tear. Every time one of these articles comes up, they forward me the link and ask whether that's something they could use. Of course, I always have to be the one giving the bad news.

I rarely see any of those articles materialize in a way where I could say "yes, this is something I can get right now". The only one I remember actually making it is the Argus II, and even then there is no way I could afford the $150K price.

aent• 6 years ago

Closest you can get are probably podcasts with those researches, for example https://peterattiamd.com/podcast/

alex-lx• 6 years ago

I am a glaucoma patient for 2 years and I'm 30. I hope there will be a cure before I lose my sight.

Sight restored by turning back the epigenetic clock

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