Production Quality is over the top, the Animations are great, the Pacing is fast yet allows time for intuition... I really don´t understand how the Algorithm could have missed such a sure hit... I really hope this Channel gets the momentum it deserves!
It's funny because in the 8 days since you left this comment--the algorithm really started picking up this whole channel. Just in time for me to launch season 2 next month. Kudos!
@@Clockworkbio the algorithm really seems to like you now because i just got recommended your video on atp synthase and was blown away by your great videos and how they were missed. at the same time i was kinda sad when i saw that the last upload has been 3 years so hearing abvout season 2 is great news! Great content! Thank you
Telomerase is not only found in cancer cells but in most cells that need to divide a lot for some purpose. Here are some exmples: stem cells have, the cells just before your nails have telomerase, the ones from the basal skin layer, intestinal crypt proliferative zone, all hair follicles and etc
@@narrativeless404 Your skin, hair and nails also grow thinner(one of the reasons causing balding) and why old people has skin that tears easier. There are a couple of reason the main one is this: Changes in Stem Cell Microenvironment: Stem cells reside in specialized microenvironments within tissues known as niches. The aging process can alter these niches, affecting the signals and support structures that regulate stem cell function. Changes in the stem cell microenvironment can impair stem cell activity and reduce their regenerative potential. If you want the other reasons too just say and I will comeback but the answer will be around 4x as big
@@narrativeless404 Even though stem cells have telomerase and can in theory divide forever, they aren't invulnerable. Other factors can impact their ability to divide, and they can get damaged, and killed, by other things. Replacing lost stem cells still requires energy and time (and most stem cells are SLOW dividing cells.They actually take more time to divide and replace themselves than many other cell types, even if they have the capacity to do so without a numerical limit), and as we get older our ability to provide that energy and time diminishes, for a variety of reasons. As a result the rate of stem cell loss eventually exceeds the rate of stem cell replacement, so total stem cell numbers go down. Hair and nails, on the other hand, aren't made of cells, but rather BY cells. They are composed on non-living materials that certain cells produce and secrete, and assemble into the hair and nail structures outside of the cells. So their continued growth is not directly dependent on continued cell division. So long as the cells making the hair and nails are still around, alive, and doing their thing, they will make more hair and nail materials, and the hair and nails will grow, even if the cells themselves aren't dividing into more cells.
Why does this video have soo little views!?!??! Oh my god you're an absolute meiracle worker! I love learning about this! I found your ATP synthase video first... this is my 3rd video... I hope your whole channel is filled with these!
that little quieting, the chilly forboding feeling... that's existential dread. I had to turn to antidepressants when that exact thing crippled me mentally.
Antidepressants do nothing for existential dread. That's the kind of thing you just have to come to terms with by reshaping your cognitive beliefs. Trust me I've been on em. Antidepressants also don't keep me from being depressed about as often. It just makes depression more of an empty numbness instead of a crushing unbearable weight of suffering. If you're managing to just numb that out, what else are you numbing out? Antidepressants are good for not killing your self but they won't really change your outlook on life.
@@Dude8718 I respect your experiences, especially given how often the experiences of someone on an antidepressant will be both subjective and vary wildly between different modes of effect, but I gotta say that your experience here isn't quite universal (though it is likely quite common and worth respecting). It is definitely worth pointing out though, since a good few folk are just... very resistant to most practical antidepressants and share the experience you describe. Your experience sounds reasonably similar to my first time on an antidepressant - a first-line SSRI - and i stopped that one a year in after determining it wasn't helping and i felt just numb and empty. other lifestyle changes like diet, exercise, etc were more effective as they often will be, though i struggled to make those changes due to the combination of mental effects i was fighting. I would like to add that I've tried three different medications - two were SSRIs which for me didn't really help much, and then after some deep research into modes of effect, and a year of being absolutely crippled with existential crisis related panic attacks (despite extensive therapy and genuine effort) I took a chance on a SNRI based solely on an ADHD friend who had a good experience with one and, honestly, because i had nothing left to lose. It has a couple side effects but i can live with them - and i was fortunate enough that by 4 weeks in i was genuinely noticing a huge positive change. Intrusive existential dread and panic attacks started rapidly becoming easier to channel and diffuse, coming less often and with less severity, without crippling my emotions at all. It absolutely saved my life, and enabled me to start making exactly those changes to lifestyle and mindset that you mentioned helping you. It was literally a night and day difference and without it I have zero doubt that I'd be just as crippled now as I was before i tried it. It takes a lot of patience, trust and luck to get access to an antidep that actually helps for a lotta folk, and while some folk aren't able to, sometimes it's worth trying a different kind to see if there's a difference.
@@Dude8718 the tl;dr is: it absolutely worked for me, but only after i switched from SSRI to SNRI out of desperation. If you've tried both and had equally bad experiences on both, i feel for ya, that sucks :c
Don't worry too much,,, be happy the universe gave u a chance to experience life happiness and fulfillment,,,,, with time you will realise how much potential you have and how much positive stuff life has to offer,, A lot of times it's about the mindset one has. , If one thinks life sucks and everything is useless, life will suck, you will not even get a chance to see the good because youre seeing life through a polarising fulter that cuts out the happy stuff, , if one tries to see the good, if one tries to be humble, without letting the ego dissatisfy you about everything and ruin everything, you will learn to accept yourself , the world , life is not fair , but you will be grateful for what you have. Sorry, I don't know you but I just wanted to help, if this made you feel bad, ignore what I said
About the telomerase causing cancer though - I've read papers about testing the upregulation of TERT in-vivo (usually in mice), and all of them that I recall reported an increase in lifespan with no increase in cancer risk at all. So maybe it's correlation, not causation? Though if I understand correctly, just increasing telomerase still isn't enough to make you completely immortal, as the mice only ever got around a 20-30% increase in lifespan from the control. Other issues like thymus involution and DNA damage accumulation end up happening regardless of telomere length, so there's definitely more issues that need to be worked out before an immortality pill comes to market. But, I'm still hopeful that we'll figure it out. Supposedly germline cells (the ones that make gametes) have no trouble maintaining their genome at all, so maybe we can borrow some of their goofy shenanigans to use in our other cells?
There are potential medical ideas around it. Maybe we copy a person's DNA into artificial storage, then medical aging reversal by artificially infusing cells with the original DNA and long telomeres into your body. It would require regular medical treatments, but I'd be ok with that.
A big issue with those mouse studies is they use breeds that have unusually short lifespans compared to a normal mouse. This makes sense, as otherwise studies would take 2-3x longer than they could have. The issue is, a lot of these studies aren’t reproducible in the native mouse breeds that have a normal lifespan, which throws into question whether these sorts of treatments have a fundamental benefit, or are only counteracting the accelerated aging of those certain breeds.
yes it isnt enough, other than DNA damage theres also epigenetic alteration due to side effect of DNA repair process, so suppres DNA damage itself still not suificient, we need to keep everything back after some shit strike
how are you not getting millions of views? You are close to kugrzact level of quality, more informative, with so many more good defining features, like exploring life not just from a science view, but a philosophical one too. Love your channel, man
Good to see your channel getting the attention it deserves! I can tell you seriously put so much effort and quality work into these videos and I look forward to someday when I search a bio term on UA-cam and yours is the first to show up like some of the other big science channels!
fixing problems in our biology like this to fight ageing. is something I hope to dedicate my life to one day. as Isaac Arthur once said either cure ageing or die trying.
In the opening 30 seconds of the intro monolog, I find your word choice interesting... "The evolutionary process that designed us." It is striking in its fundamental meaning with a twist of poetic irony.
I know that smell. It is the smell of hard-work and success. Great video. Really interesting in all its aspect. I won't pretend I understood everything about the dna replication concept, but I sure learned a lot of other things
Really inspiring video, your enthusiasm and wonder with regards to biochemistry is really infectious! I love how the video is based mostly on the audio and content with the figures and animations used as just visual aid, something that I can definitely think about in my videos. Keep up the awesome work!
UA-cam needs more of this (this is an elaborate bump)! A great blend of accessible intracellular biology info and the artistic knowledge to keep people engaged.
Naw friend--you're just beating the algorithm! UA-cam is slow, but fair enough eventually. Feel free to share this video around if you want to help push the algo in the right direction!
For me this video was not a downer at all, for me it was a reminder that life is imperfect, there is room for more, we can fix it, it gives me hope of sorts
If this is the type of content and knowledge I'm getting from you. I am 100% ready for you to take all of my life's time so that untill all my telemerase are gone , I want to know as much about life and consciousness that I'm having throughout my life. ❤❤❤🥰🥰.. please comeback to youtube and make more contents like these
if there was some sort of fault detect that deactivated telomerase, perhaps a non-indefinite extension of cell lifespan could occur, where a cell replicates, gets told to stop after a chemical signal, like normal, but telomerase is still enabled to prevent dna destruction until a break detection signal is found, and then it is deactivated. telomerase seems good on paper until you realize it works against the dna damage protection methods if it is always active. just a thought, but if it could be modified to dynamically activate and deactivate based on existing fault detection, it might be able to safely slow cellular aging processes, then again that's just a hypothesis, and would be beyond my understanding to test in a lab.
Is telomerase used during meiosis or fertilisation then? I've always wondered how babies are born with full telomeres when their parents must have accumulated quite a bit of telomere damage already. I guess the germ cells set aside to become sperm or eggs could be set aside early on and not divide until they're needed, but still, over generations those cell divisions would build up... does telomerase reset the clock, so to speak, when gametes are made?
Oh dang I remember OBSESSING over this when I was writing the script. I've been working so much on plant biology that it kinda pushed the memory of this out of my head. Let me roll through my research and I'll reply again!
You're right on the money. Basically telomerase is only active in gametes and cancerous cells, with very little expression in somatic cells (possibly haematopoietic stem cells and activated B-cells).
@@kafuuchino3236 probably both, so it'll have to be very speciically delivered and dosed. I see more possibilities for regrowing nerves and tissues with telomerase than fighting all encompassing ageing.
Great video! Found it over on /r/mealtimevideos. Very informative in the EILI10 manner which I think you intended, which is about the limits of my capabilities of understanding. Subbed. I love what you said about consciousness at the end. Still going to fight off the existential doom feelings for the rest of the day, but thats not completely your fault
Oh my god you have no idea how valuable this comment is. I've been so nervous posting on r/mealtimevideos because I have no idea if this style will be valuable to anyone outside of the bio subreddits. Thank you so much for being so generous with your time. I won't forget this.
This whole issue of DNA replication being unable to copy that last bit of the chromosome ultimately exists because we eukaryotes have linear chromosomes. Prokaryotes have circular chromosomes, and in a circular chromosome there is no problem, as there will always be leading DNA for those RNA primers to stick to. DNA replication almost certainly first evolved in proto-prokaryotes with circular chromosomes, so this issue of DNA loss with replication would not have come up. When the first eukaryotes emerged after their two bacterial and archaean ancestor prokaryotes merged, somehow the original prokaryotic circular chromosome got chopped up into multiple lineage chromosomes, giving rise to this problem. The whole system with telomeres and telomerase was a kluge that early eukaryotes came up with to deal with the new problem. This may also be one of the reasons Eukaryotes have a lot of junk DNA, while Prokaryotes don't. Because telomeres are basically a type of junk DNA that happens to exist at the end of chromosomes, and very likely evolved out of the same mutational mechanisms that produce certain classes of junk DNA, and the telomerase gene very likely a descendant of a type of selfish parasitic jumping gene that produces junk DNA as a byproduct of its activity. The same mechanisms that prokaryotes use to identify and remove junk DNA from their genomes would very likely recognize telomeres as junk and remove them too, so eukaryotes would have had to turn them off/decrease their activity to avoid losing their telomeres prematurely.
I learned a lot in this video! RNA primers on the lagging strand, the T-loop at the end of chromosomes, and the TTAGGG sequence in telomeres (I was taught it was AAAAAA). Great educational merit, and your diagrams really helped. Thanks for doing the work of assembling and sharing this video!
The AAAAAA sequence you're thinking of is the Poly-A tail, which gets added to the 3' end of mRNA after eukaryotic transcription. I can definitely see why it's easy to get confused between the two haha-- they're both sequences that are "added" after a polymerization reaction regarding DNA
I am going through theese fascinating videos made 3 years ago, which somehow surfaced again right now and it makes me sad that this channel produced only a dozen or so videos and then stopped. Any chance for a reboot?
@Clockworkbio That's great news! I didn't dare to hope that, I thought you must be busy with some kickass project. But how is it possible for the old videos to resurface now? Is it because of new scheduled videos?
What an awesome video! I have one question though: why does senescence not occur in every eukaryotic cell that ever divides? Such as sex cells? The key difference between sex cells and every other cell is meiosis and recombination, and since any life posessing linear chromosomes did not go extinct after 50 generations, there must be some regulated repair going on at some point in our life cycles.
In order to make sure that I'm making videos that are actual valuable to folks teaching Biochem--I had to make the transition to animating in 3d. That took WAY longer than expected. But I am making new videos and Season 2 will launch in June. See you then!
It's actually goddamn amazing that "life just works". The more I learn about it, the more I realise that it's just a MASSIVE hack. It's like a junior programmer trying to get shit done before a tight deadline... Oh, the copying process is a bit buggy - ok, let's invent the DNA police Oh but wait, now we have these bits over here that shouldn't be repaired - ok, let's just HIDE them from the DNA police lol Oh but everything is still buggy - ok, let's just limit self replication to 50 times haha I mean come on it's ridiculous :D
Maybe, from the viewpoint of evolution, there is some reason or even necessity that an individual does not live forever. But right here, right now, it is our time 💪
Sorry to be that guy (🤓☝️) but I was a little bothered by 2:38 because you imply that the 3' OH is the leaving group when it's actually the nucleophile, which attacks an NTP and kicks out PPi to energetically drive the reaction forward. It's a small detail, but seeing the phosphate kick out a hydroxyl just feels wrong lmao. Otherwise, amazing video! I look forward to watching more of your stuff
If it theory than maybe life itself is side product but paradoxically the universe has all the fine tuning to produce a side product and a really good self repairing one
And all I gotta do is keep up with your upload pace and then we'll REALLY be in business. Thanks so much--it really means a lot. I love this comment section so much--check out all these biotubers y'all!
Great video! I really appreciate your work and your want to educate people. However, sometimes the narrator talk too fast, like in 5:58. It would be good if they slowed down a little bit.
I can confirm the narrator has significantly reduced their caffeine intake before recording all future videos and is recording these at a more measured pace.
So to add a kind of dark humor twist on it, we just need to invent a better biochemical spell checker to make the padding on the end of the chromosomes obsolete so it doesn't have to get lopped off every time a cell divides.
It is interesting that the only normal thing that can replicate all the necessary information when it is made is the egg. It contains pretty much everything which will then cause the (positive) domino effect.
I do a lot of mutagenisis in my undergrad and I hope to do more as I go further but kinda "playing god" with DNA has really taught me how fragile life is and how amazingly optimized most life is after the massive amount of time evolution needed to take place. I would love to live forever and work on understanding life and how we exist but hopefully death can be used more as a way to appreciate that existence and complexity instead of driving fear
Maybe consciousness is not a side effect of evolution, maybe consciousness is the central thing in the universe. Maybe we are the main thing in the universe (including all consciousness beings) Can you do something on subjective experience? I think we all think about death and I would like to know more about perception and therefore what happens at death, I think it would be cool if you made a video like that. I think the universe is very mysterious and fundamentally unknownable, I don't really accept that we are just a side thing that happend, maybe we are all good Yeah subjective Experience video pls, i think your stuff is so cool ❤
Just subscribed, great stuff. Life, the why and how is indeed the latest great frontier of science. The molecular level boggles the mind, and then there is the question of macrostructures. How can these cells communicate to consistently build a hand, foot, or body? There ought to be many more folks working on this but our form of Capitalism prefers to develop GLP-1 instead.
10:31 At 40.... 🤷🏽♂️ ... I don't *_want to die,_* but I'm not scared of it. I feel 'blessed' to be a conscious part of the universe. That's enough for me. It's been a great life thus far (and hope it continues for a long time) but.... realistically: I feel like I'm doing better than I likely deserve (what did I do to deserve such a great life while other people suffer? nothing. so, all things considered, they likely deserve the luxuries I have...especially those I'm not aware that I take for granted. It's not a bad thing, just a different way to look at how lucky I am).
So cells *do* have a set amount of times they can divide. Many years ago when I was a kid, I had it in my mind from somewhere that cells had these little tails and when those ran out, they couldn’t divide anymore. I’m sure whatever that was originated from someone telling me the basic idea of this process.
That short lifespan is/was mostly recorded in cities, where young disperse to and where exposure to communicable diseases vastly increases. numerous other events, like increased competition, violence, resultant depression and other phenotypic events induce difficulties, dysfunction, malassociations with/as organized perpetrators and targets, of violence, toxins, polluting chemicals. (increased
makes me wonder if there could be any way of perserving conciousness in cancer (probably with cybernetics or something), but i imagine even if you could stay alive as cancer you may end up just as a blob able to experience nothing but pain. some real "i have no mouth and i must scream" type shit
Cancer is cells that both induce greater formation of blood vessels, and turn off apoptosis-related genes. They hog your energy. Consciousness happens to be a brain's self monitoringin relation to novel sensory information, and when parts of a brain die, self-monitoring diminishes until cessation. There is NO consciousness outside that monitoring of change, even when consciousness is described as actions in a single cell, which consciousness can be described as continuing organized metabolism. Pain is a brain's monitoring of hpc neural reports of toxic heat, toxic cold, and toxic pressure or pinch. Glutamate signaling to other neurons, activating certain connected cells in specific parts of a brain, are involved in pain sensing. There is NO separate recognition or separate consciousness. This is why psychopaths and narcissists will NEVER imagine nor feel your pain for you. If you have ever been healing from injury or surgery, drugs interfering with pain sensing block it. From the comment, a few more years of biology, from atomic charges up through experiments and records of brain lesions are in order for its writer.
So to sum that shit up: It needs some actual intelligence to interfere and find how to fix things up so it doesn't look like a bunch of broken buggy code Basically a bunch of useless "0xFF" instructions in the end of the programs that exist only for alignment or some other niche shitty purpose and without which it can totally function fine, except if it wasn't actually crashing at some point when they aren't there anymore because it was meant to have them Everything would've been fine if the same program didn't occasionally just OVERWRITE some portion of them with zeros every once in a while Removing this without knowing what it does is not great either, because even if you want less old cells, you don't want cells to reproduce out of control either Evolution just patched the shit in the most hacky, lazy and inefficient way possible - by just cutting the replication code off until it stops working
You just asked an awesome question that leads to hundreds of other really interesting little problems. Keep asking that same kind of question enough and you'll end up with a PhD in Molecular Biology or something.
I think there are cancer prevention mechanisms too so just crank cancer prevention to maksimum make replicating bit inefficient and this turn off this planned death thing
The constalation of enzymes at what point in time did they evolve because seemingly dna could not have functioned properly without, everything hase to be in place for it to work
8:00 life expectancy 25... well yes, but that is the average and vast majority died as infants and toddlers, well before reproduction. If you survived to age of 15 years, you would have expected to live as 50 - 60 years old. So, that is not the explanation.
@@user255 I don't think he was talking about the mechanism, he gave the mechanism in the first half of the video and even then, he mentioned that it could just be a whole big coincidence. The statement about life expectation in itself isn't an explanation but a supportive argument saying 'If you look at it from the evolutionary perspective, it makes sense that our cells are only trying to get us to the point when we're old enough to reproduce'. This is what I interpreted, I'd love to know why you said what you said.
if your telomeres are just repeating instructions... why not... just rebuild those instructions once every decade... boom ive solved aging. no cancer since the telomerase isnt permanant
"Each little nucleotide also has an OH group on the side here... like right here."
Me: OH
Ugh I knew somebody was gonna dunk on me if I didn't re-record that line -_-
Love this!❤
Production Quality is over the top, the Animations are great, the Pacing is fast yet allows time for intuition... I really don´t understand how the Algorithm could have missed such a sure hit... I really hope this Channel gets the momentum it deserves!
It's funny because in the 8 days since you left this comment--the algorithm really started picking up this whole channel. Just in time for me to launch season 2 next month. Kudos!
@@Clockworkbio the algorithm really seems to like you now because i just got recommended your video on atp synthase and was blown away by your great videos and how they were missed. at the same time i was kinda sad when i saw that the last upload has been 3 years so hearing abvout season 2 is great news!
Great content! Thank you
Best find of 2024🎉
@@Clockworkbio i got your videos recommended too and i shared link to them with a friend
We are eagerly waiting for season 2!!!
"A machine can still work even if it has busted instructions" LMAO yeah
I mean, most software is just that
"It just works" until it breaks for a stupid reason that's written in it, yet comes out unexpected
Only discovered this channel now ??
This deserves way more likes and views.
This is quality peak !
"Consciousness is a bizarre and unintended side effect of evolution" - best line I've heard today
True
Telomerase is not only found in cancer cells but in most cells that need to divide a lot for some purpose. Here are some exmples: stem cells have, the cells just before your nails have telomerase, the ones from the basal skin layer, intestinal crypt proliferative zone, all hair follicles and etc
If that's the case, why do we get less stem cells as we grow older, but the useless shit like nails and hair keeps growing?
@@narrativeless404 Your skin, hair and nails also grow thinner(one of the reasons causing balding) and why old people has skin that tears easier.
There are a couple of reason the main one is this:
Changes in Stem Cell Microenvironment: Stem cells reside in specialized microenvironments within tissues known as niches. The aging process can alter these niches, affecting the signals and support structures that regulate stem cell function. Changes in the stem cell microenvironment can impair stem cell activity and reduce their regenerative potential. If you want the other reasons too just say and I will comeback but the answer will be around 4x as big
@@nicholasfigueiredo3171 Yes, i know
But they do somewhat still grow as far as I know
Nah, I'm good with that, thanks 👍
@@narrativeless404 Even though stem cells have telomerase and can in theory divide forever, they aren't invulnerable. Other factors can impact their ability to divide, and they can get damaged, and killed, by other things. Replacing lost stem cells still requires energy and time (and most stem cells are SLOW dividing cells.They actually take more time to divide and replace themselves than many other cell types, even if they have the capacity to do so without a numerical limit), and as we get older our ability to provide that energy and time diminishes, for a variety of reasons. As a result the rate of stem cell loss eventually exceeds the rate of stem cell replacement, so total stem cell numbers go down.
Hair and nails, on the other hand, aren't made of cells, but rather BY cells. They are composed on non-living materials that certain cells produce and secrete, and assemble into the hair and nail structures outside of the cells. So their continued growth is not directly dependent on continued cell division. So long as the cells making the hair and nails are still around, alive, and doing their thing, they will make more hair and nail materials, and the hair and nails will grow, even if the cells themselves aren't dividing into more cells.
Why does this video have soo little views!?!??! Oh my god you're an absolute meiracle worker! I love learning about this! I found your ATP synthase video first... this is my 3rd video... I hope your whole channel is filled with these!
that little quieting, the chilly forboding feeling... that's existential dread. I had to turn to antidepressants when that exact thing crippled me mentally.
Antidepressants do nothing for existential dread. That's the kind of thing you just have to come to terms with by reshaping your cognitive beliefs. Trust me I've been on em. Antidepressants also don't keep me from being depressed about as often. It just makes depression more of an empty numbness instead of a crushing unbearable weight of suffering. If you're managing to just numb that out, what else are you numbing out? Antidepressants are good for not killing your self but they won't really change your outlook on life.
@@Dude8718 I respect your experiences, especially given how often the experiences of someone on an antidepressant will be both subjective and vary wildly between different modes of effect, but I gotta say that your experience here isn't quite universal (though it is likely quite common and worth respecting).
It is definitely worth pointing out though, since a good few folk are just... very resistant to most practical antidepressants and share the experience you describe.
Your experience sounds reasonably similar to my first time on an antidepressant - a first-line SSRI - and i stopped that one a year in after determining it wasn't helping and i felt just numb and empty. other lifestyle changes like diet, exercise, etc were more effective as they often will be, though i struggled to make those changes due to the combination of mental effects i was fighting.
I would like to add that I've tried three different medications - two were SSRIs which for me didn't really help much, and then after some deep research into modes of effect, and a year of being absolutely crippled with existential crisis related panic attacks (despite extensive therapy and genuine effort) I took a chance on a SNRI based solely on an ADHD friend who had a good experience with one and, honestly, because i had nothing left to lose.
It has a couple side effects but i can live with them - and i was fortunate enough that by 4 weeks in i was genuinely noticing a huge positive change. Intrusive existential dread and panic attacks started rapidly becoming easier to channel and diffuse, coming less often and with less severity, without crippling my emotions at all.
It absolutely saved my life, and enabled me to start making exactly those changes to lifestyle and mindset that you mentioned helping you.
It was literally a night and day difference and without it I have zero doubt that I'd be just as crippled now as I was before i tried it.
It takes a lot of patience, trust and luck to get access to an antidep that actually helps for a lotta folk, and while some folk aren't able to, sometimes it's worth trying a different kind to see if there's a difference.
@@Dude8718 the tl;dr is: it absolutely worked for me, but only after i switched from SSRI to SNRI out of desperation. If you've tried both and had equally bad experiences on both, i feel for ya, that sucks :c
Don't worry too much,,, be happy the universe gave u a chance to experience life happiness and fulfillment,,,,, with time you will realise how much potential you have and how much positive stuff life has to offer,, A lot of times it's about the mindset one has. , If one thinks life sucks and everything is useless, life will suck, you will not even get a chance to see the good because youre seeing life through a polarising fulter that cuts out the happy stuff, , if one tries to see the good, if one tries to be humble, without letting the ego dissatisfy you about everything and ruin everything, you will learn to accept yourself , the world , life is not fair , but you will be grateful for what you have.
Sorry, I don't know you but I just wanted to help, if this made you feel bad, ignore what I said
@@emigoldber this is really well spoken
About the telomerase causing cancer though - I've read papers about testing the upregulation of TERT in-vivo (usually in mice), and all of them that I recall reported an increase in lifespan with no increase in cancer risk at all. So maybe it's correlation, not causation?
Though if I understand correctly, just increasing telomerase still isn't enough to make you completely immortal, as the mice only ever got around a 20-30% increase in lifespan from the control. Other issues like thymus involution and DNA damage accumulation end up happening regardless of telomere length, so there's definitely more issues that need to be worked out before an immortality pill comes to market.
But, I'm still hopeful that we'll figure it out. Supposedly germline cells (the ones that make gametes) have no trouble maintaining their genome at all, so maybe we can borrow some of their goofy shenanigans to use in our other cells?
True
Shit's getting corrupted eventually still
So does that mean senescence is just a stupid glitch with no purpose?
There are potential medical ideas around it.
Maybe we copy a person's DNA into artificial storage, then medical aging reversal by artificially infusing cells with the original DNA and long telomeres into your body.
It would require regular medical treatments, but I'd be ok with that.
A big issue with those mouse studies is they use breeds that have unusually short lifespans compared to a normal mouse. This makes sense, as otherwise studies would take 2-3x longer than they could have. The issue is, a lot of these studies aren’t reproducible in the native mouse breeds that have a normal lifespan, which throws into question whether these sorts of treatments have a fundamental benefit, or are only counteracting the accelerated aging of those certain breeds.
yes it isnt enough, other than DNA damage theres also epigenetic alteration due to side effect of DNA repair process, so suppres DNA damage itself still not suificient, we need to keep everything back after some shit strike
I've always been so fascinated with this part of biology and how messy this effective process actually is. Thank you and keep going please.
how are you not getting millions of views?
You are close to kugrzact level of quality, more informative, with so many more good defining features, like exploring life not just from a science view, but a philosophical one too.
Love your channel, man
came from John Green.,, loved this video!
Thank you so much! Completely blown away by the response from the rest of nerdfighteria! Hope you like the rest of them too!
love the script as well.. connecting humane and human..
@@Clockworkbio remember you human species with a bit broken and beautiful DNA... you deserve this.
Good to see your channel getting the attention it deserves! I can tell you seriously put so much effort and quality work into these videos and I look forward to someday when I search a bio term on UA-cam and yours is the first to show up like some of the other big science channels!
“I am the middle of an unfinished process” unexpectedly profound and I appreciate your insight, thanks for the surprise philosophy lol
Great video as always! (And it def raises the bar for me haha since I'm also in the midst of making a DNA vid atm >.
Miss you bud. Hope you start posting again soon!
@@Clockworkbioyikes! Telemere transplant?
fixing problems in our biology like this to fight ageing. is something I hope to dedicate my life to one day. as Isaac Arthur once said either cure ageing or die trying.
In the opening 30 seconds of the intro monolog, I find your word choice interesting... "The evolutionary process that designed us." It is striking in its fundamental meaning with a twist of poetic irony.
Yep
It mocks religion
What about that?
Found your video on the biochemistry subreddit and I love it, gonna watch each video every day or so and hope you make more in the future!
I know that smell. It is the smell of hard-work and success.
Great video. Really interesting in all its aspect. I won't pretend I understood everything about the dna replication concept, but I sure learned a lot of other things
For those of you interested, look up the trombone model of DNA replication to understand the physics of how weird lagging strand synthesis actually is
Really inspiring video, your enthusiasm and wonder with regards to biochemistry is really infectious! I love how the video is based mostly on the audio and content with the figures and animations used as just visual aid, something that I can definitely think about in my videos. Keep up the awesome work!
This video is so good. I love the chaos that makes us alive. Thank you. 🙏
UA-cam needs more of this (this is an elaborate bump)!
A great blend of accessible intracellular biology info and the artistic knowledge to keep people engaged.
Sacrificing this comment to the algorithm
Here's another one from me
Take mine too
So much for the Intelligent Design theory!
youtube algo failing this video
Naw friend--you're just beating the algorithm! UA-cam is slow, but fair enough eventually. Feel free to share this video around if you want to help push the algo in the right direction!
For me this video was not a downer at all, for me it was a reminder that life is imperfect, there is room for more, we can fix it, it gives me hope of sorts
If this is the type of content and knowledge I'm getting from you. I am 100% ready for you to take all of my life's time so that untill all my telemerase are gone , I want to know as much about life and consciousness that I'm having throughout my life. ❤❤❤🥰🥰.. please comeback to youtube and make more contents like these
10:53 This is deep. Respect
Hey, i only found you because of John Green, now you got a new Follower!
Very deep analysis.
if there was some sort of fault detect that deactivated telomerase, perhaps a non-indefinite extension of cell lifespan could occur, where a cell replicates, gets told to stop after a chemical signal, like normal, but telomerase is still enabled to prevent dna destruction until a break detection signal is found, and then it is deactivated. telomerase seems good on paper until you realize it works against the dna damage protection methods if it is always active. just a thought, but if it could be modified to dynamically activate and deactivate based on existing fault detection, it might be able to safely slow cellular aging processes, then again that's just a hypothesis, and would be beyond my understanding to test in a lab.
Is telomerase used during meiosis or fertilisation then? I've always wondered how babies are born with full telomeres when their parents must have accumulated quite a bit of telomere damage already. I guess the germ cells set aside to become sperm or eggs could be set aside early on and not divide until they're needed, but still, over generations those cell divisions would build up... does telomerase reset the clock, so to speak, when gametes are made?
Oh dang I remember OBSESSING over this when I was writing the script. I've been working so much on plant biology that it kinda pushed the memory of this out of my head. Let me roll through my research and I'll reply again!
I think that telomerase is functional in gametes and not functional in somatic cells? Just guessing.
You're right on the money. Basically telomerase is only active in gametes and cancerous cells, with very little expression in somatic cells (possibly haematopoietic stem cells and activated B-cells).
@@Tinky1rs Could telomerase help with anti-ageing then or would that just leave us too susceptible to cancer?
@@kafuuchino3236 probably both, so it'll have to be very speciically delivered and dosed. I see more possibilities for regrowing nerves and tissues with telomerase than fighting all encompassing ageing.
Incredible videos. Thank you for making these
Great video! Found it over on /r/mealtimevideos. Very informative in the EILI10 manner which I think you intended, which is about the limits of my capabilities of understanding. Subbed.
I love what you said about consciousness at the end. Still going to fight off the existential doom feelings for the rest of the day, but thats not completely your fault
Oh my god you have no idea how valuable this comment is. I've been so nervous posting on r/mealtimevideos because I have no idea if this style will be valuable to anyone outside of the bio subreddits. Thank you so much for being so generous with your time. I won't forget this.
this is amazing! I love your animations for the DNA and the proteins in the beginning
Great video!
I'm sure we'll fix this mess eventually
This whole issue of DNA replication being unable to copy that last bit of the chromosome ultimately exists because we eukaryotes have linear chromosomes. Prokaryotes have circular chromosomes, and in a circular chromosome there is no problem, as there will always be leading DNA for those RNA primers to stick to. DNA replication almost certainly first evolved in proto-prokaryotes with circular chromosomes, so this issue of DNA loss with replication would not have come up. When the first eukaryotes emerged after their two bacterial and archaean ancestor prokaryotes merged, somehow the original prokaryotic circular chromosome got chopped up into multiple lineage chromosomes, giving rise to this problem. The whole system with telomeres and telomerase was a kluge that early eukaryotes came up with to deal with the new problem.
This may also be one of the reasons Eukaryotes have a lot of junk DNA, while Prokaryotes don't. Because telomeres are basically a type of junk DNA that happens to exist at the end of chromosomes, and very likely evolved out of the same mutational mechanisms that produce certain classes of junk DNA, and the telomerase gene very likely a descendant of a type of selfish parasitic jumping gene that produces junk DNA as a byproduct of its activity. The same mechanisms that prokaryotes use to identify and remove junk DNA from their genomes would very likely recognize telomeres as junk and remove them too, so eukaryotes would have had to turn them off/decrease their activity to avoid losing their telomeres prematurely.
I like how you still pronounced the full dna meaning. Can you do more of that?
Found your videos through reddit. They're great! Keep making more.
I learned a lot in this video! RNA primers on the lagging strand, the T-loop at the end of chromosomes, and the TTAGGG sequence in telomeres (I was taught it was AAAAAA). Great educational merit, and your diagrams really helped. Thanks for doing the work of assembling and sharing this video!
The AAAAAA sequence you're thinking of is the Poly-A tail, which gets added to the 3' end of mRNA after eukaryotic transcription. I can definitely see why it's easy to get confused between the two haha-- they're both sequences that are "added" after a polymerization reaction regarding DNA
So, just commenting to tell you to keep it up. So, keep it up, I guess. Mission accomplished!
I am going through theese fascinating videos made 3 years ago, which somehow surfaced again right now and it makes me sad that this channel produced only a dozen or so videos and then stopped. Any chance for a reboot?
The only reason the videos are resurfacing right now is because season 2 is coming out in June!
@Clockworkbio That's great news! I didn't dare to hope that, I thought you must be busy with some kickass project. But how is it possible for the old videos to resurface now? Is it because of new scheduled videos?
@@Clockworkbio it is July, i still have hope, but i will of course wait!!!!
What an awesome video! I have one question though: why does senescence not occur in every eukaryotic cell that ever divides? Such as sex cells? The key difference between sex cells and every other cell is meiosis and recombination, and since any life posessing linear chromosomes did not go extinct after 50 generations, there must be some regulated repair going on at some point in our life cycles.
telomerase is especially expressed in gametes =)
tysm for this video
Why are you not making any new videos, I love your videos
In order to make sure that I'm making videos that are actual valuable to folks teaching Biochem--I had to make the transition to animating in 3d. That took WAY longer than expected. But I am making new videos and Season 2 will launch in June. See you then!
It's actually goddamn amazing that "life just works". The more I learn about it, the more I realise that it's just a MASSIVE hack. It's like a junior programmer trying to get shit done before a tight deadline...
Oh, the copying process is a bit buggy - ok, let's invent the DNA police
Oh but wait, now we have these bits over here that shouldn't be repaired - ok, let's just HIDE them from the DNA police lol
Oh but everything is still buggy - ok, let's just limit self replication to 50 times haha
I mean come on it's ridiculous :D
Maybe, from the viewpoint of evolution, there is some reason or even necessity that an individual does not live forever.
But right here, right now, it is our time 💪
Sorry to be that guy (🤓☝️) but I was a little bothered by 2:38 because you imply that the 3' OH is the leaving group when it's actually the nucleophile, which attacks an NTP and kicks out PPi to energetically drive the reaction forward. It's a small detail, but seeing the phosphate kick out a hydroxyl just feels wrong lmao. Otherwise, amazing video! I look forward to watching more of your stuff
This is really good explanation and motivation. How we being gratefull in life scientifically. Awesome work guys. Peace love and polymerase
God. this is a masterpiece.
If it theory than maybe life itself is side product but paradoxically the universe has all the fine tuning to produce a side product and a really good self repairing one
I'm so glad you posted! I love this and your animations are AMAZING 😍
And all I gotta do is keep up with your upload pace and then we'll REALLY be in business.
Thanks so much--it really means a lot. I love this comment section so much--check out all these biotubers y'all!
If 'is' follows 'ought'
it will do what they thought
In the end, we all do what we must
Great video! I really appreciate your work and your want to educate people. However, sometimes the narrator talk too fast, like in 5:58. It would be good if they slowed down a little bit.
I can confirm the narrator has significantly reduced their caffeine intake before recording all future videos and is recording these at a more measured pace.
So to add a kind of dark humor twist on it, we just need to invent a better biochemical spell checker to make the padding on the end of the chromosomes obsolete so it doesn't have to get lopped off every time a cell divides.
how to write the perfect plot twist 9:00
It is interesting that the only normal thing that can replicate all the necessary information when it is made is the egg. It contains pretty much everything which will then cause the (positive) domino effect.
Great stuff dude! Was my pleasure to have assisted in the proof-reading.
How does this "problem" not transmit through reproduction?
I do a lot of mutagenisis in my undergrad and I hope to do more as I go further but kinda "playing god" with DNA has really taught me how fragile life is and how amazingly optimized most life is after the massive amount of time evolution needed to take place. I would love to live forever and work on understanding life and how we exist but hopefully death can be used more as a way to appreciate that existence and complexity instead of driving fear
I LOVE BIOCHEMISTRY
6:00 if we somehow find a way to elongate the leading strand during replication wouldn't it connect with the single overhanging strand remained
awesome video- especially the animations! what software do you use?
Maybe consciousness is not a side effect of evolution, maybe consciousness is the central thing in the universe. Maybe we are the main thing in the universe (including all consciousness beings)
Can you do something on subjective experience? I think we all think about death and I would like to know more about perception and therefore what happens at death, I think it would be cool if you made a video like that. I think the universe is very mysterious and fundamentally unknownable, I don't really accept that we are just a side thing that happend, maybe we are all good
Yeah subjective Experience video pls, i think your stuff is so cool ❤
The life expectancy was so low in the past because a lot of babies and small children died.
Great !
Just subscribed, great stuff. Life, the why and how is indeed the latest great frontier of science. The molecular level boggles the mind, and then there is the question of macrostructures. How can these cells communicate to consistently build a hand, foot, or body? There ought to be many more folks working on this but our form of Capitalism prefers to develop GLP-1 instead.
The world is lucky to have Peter Starr Northrop.
10:31 At 40.... 🤷🏽♂️ ... I don't *_want to die,_* but I'm not scared of it. I feel 'blessed' to be a conscious part of the universe. That's enough for me. It's been a great life thus far (and hope it continues for a long time) but.... realistically: I feel like I'm doing better than I likely deserve (what did I do to deserve such a great life while other people suffer? nothing. so, all things considered, they likely deserve the luxuries I have...especially those I'm not aware that I take for granted. It's not a bad thing, just a different way to look at how lucky I am).
So cells *do* have a set amount of times they can divide. Many years ago when I was a kid, I had it in my mind from somewhere that cells had these little tails and when those ran out, they couldn’t divide anymore. I’m sure whatever that was originated from someone telling me the basic idea of this process.
This is exactly what I wanted to know
Happy to help! Feel free to drop another comment if you'd like some follow-up resources or want a deeper dive!
Enjoy Life 😊
That short lifespan is/was mostly recorded in cities, where young disperse to and where exposure to communicable diseases vastly increases. numerous other events, like increased competition, violence, resultant depression and other phenotypic events induce difficulties, dysfunction, malassociations with/as organized perpetrators and targets, of violence, toxins, polluting chemicals.
(increased
No, it was mainly due deaths of infants and toddlers. They just get sick a lot, everywhere.
Visual studio code-powered dna
It's weird that there are like 65% from four years and 30% from this week
I just need one more life? ... now, I can get it right this time. Telomerase me!
makes me wonder if there could be any way of perserving conciousness in cancer (probably with cybernetics or something), but i imagine even if you could stay alive as cancer you may end up just as a blob able to experience nothing but pain. some real "i have no mouth and i must scream" type shit
Cancer is cells that both induce greater formation of blood vessels, and turn off apoptosis-related genes. They hog your energy.
Consciousness happens to be a brain's self monitoringin relation to novel sensory information, and when parts of a brain die, self-monitoring diminishes until cessation. There is NO consciousness outside that monitoring of change, even when consciousness is described as actions in a single cell, which consciousness can be described as continuing organized metabolism.
Pain is a brain's monitoring of hpc neural reports of toxic heat, toxic cold, and toxic pressure or pinch. Glutamate signaling to other neurons, activating certain connected cells in specific parts of a brain, are involved in pain sensing.
There is NO separate recognition or separate consciousness. This is why psychopaths and narcissists will NEVER imagine nor feel your pain for you.
If you have ever been healing from injury or surgery, drugs interfering with pain sensing block it.
From the comment, a few more years of biology, from atomic charges up through experiments and records of brain lesions are in order for its writer.
stem cells express telomerase they are not cancer
So to sum that shit up:
It needs some actual intelligence to interfere and find how to fix things up so it doesn't look like a bunch of broken buggy code
Basically a bunch of useless "0xFF" instructions in the end of the programs that exist only for alignment or some other niche shitty purpose and without which it can totally function fine, except if it wasn't actually crashing at some point when they aren't there anymore because it was meant to have them
Everything would've been fine if the same program didn't occasionally just OVERWRITE some portion of them with zeros every once in a while
Removing this without knowing what it does is not great either, because even if you want less old cells, you don't want cells to reproduce out of control either
Evolution just patched the shit in the most hacky, lazy and inefficient way possible - by just cutting the replication code off until it stops working
NICE! highlight of the week!
I have faith before 9:00
Amazing 😻
Why can't I just inject telomerase then to fix the problem?
You just asked an awesome question that leads to hundreds of other really interesting little problems. Keep asking that same kind of question enough and you'll end up with a PhD in Molecular Biology or something.
what about naked mole rats bro. Please make a video it's very cool
I think there are cancer prevention mechanisms too so just crank cancer prevention to maksimum make replicating bit inefficient and this turn off this planned death thing
Wow
i love you clockwork,,,, mwah
yay!
Ah shit we gonna die 😂 shit hits hard at 30 bro
Life…er…finds a way…
Way do hydra's don't age
Gotta make the tumor work.
“They’re called cancer cells” 😭😭😭
The constalation of enzymes at what point in time did they evolve because seemingly dna could not have functioned properly without, everything hase to be in place for it to work
Amor Fati
Memento Mori
Bump
You're doing God's work, purple. Thanks so much for the help!
Just doing my part :P
God's work?? Interesting comment from a neodarwinist@@Clockworkbio
8:00 life expectancy 25... well yes, but that is the average and vast majority died as infants and toddlers, well before reproduction. If you survived to age of 15 years, you would have expected to live as 50 - 60 years old. So, that is not the explanation.
Explanation of what?
@@xyz8697 Explanation for mechanisms that cause aging.
@@user255 I don't think he was talking about the mechanism, he gave the mechanism in the first half of the video and even then, he mentioned that it could just be a whole big coincidence. The statement about life expectation in itself isn't an explanation but a supportive argument saying 'If you look at it from the evolutionary perspective, it makes sense that our cells are only trying to get us to the point when we're old enough to reproduce'. This is what I interpreted, I'd love to know why you said what you said.
if your telomeres are just repeating instructions... why not... just rebuild those instructions once every decade... boom ive solved aging. no cancer since the telomerase isnt permanant
If the telomere's nucleotides do not make a functioning gene, it does not contain "instructions"
You haven't solved anything at all.