This was a great video on the importance of paradigms in science and an interesting discussion about the hallmarks! Well done! We were very happy to work with you on this topic :)
@TheSheekeyScienceShow
3 жыл бұрын
Thank you!! Likewise, was an interesting topic to discuss! Make sure you check out LifeXtenShow's video too!
@AiternusCorp
3 жыл бұрын
Love it! 👏
@rejuvenecer_atlas
3 жыл бұрын
Just like your videos!
@waiminglee8672
Жыл бұрын
ez3z
@BrentNally
3 жыл бұрын
Great video as always! We definitely need consensus on how to solve the human aging problem ASAP so there’s much work to be done 😬
@AiternusCorp
3 жыл бұрын
Hey Brent! Love your work!
@SolvingAging
3 жыл бұрын
You did an amazing interview with Eleanor! I learned so much and love Eleanor even more now!
@BrentNally
3 жыл бұрын
@@SolvingAging Thanks. It was an honor to interview Eleanor
@kral3046
3 жыл бұрын
So glad to see Aubrey's work in this channel! His main criticism of the Hallmarks of Aging paper has been that there is 0 mention of Extracellular Matrix Stiffening (Advanced Glycation End Products that form when sugar interacts with proteins and creates crosslinks that are problematic when not cleaved, main one in Humans being Glucosepane which accounts for %90 of AGE's at least in the skin, SENS Foundation spun-off a company called Ravel Pharmaceuticals that have made some but appreciable progress in the last few years.). Also quite surprised that you haven't read his book yet as it was the first book that i read when i for the first time got serious and went down the rabbit hole of aging last year :D He has infamously been giving a time line for the Longevity Escape Velocity (which he has lowered down to just 15 years with %50 now!) but he also states that there is a %10 chance that we won't reach L.E.V in 100 years which would most likely be because of a major global catastrophe or if the Types of Damage table (or Hallmarks of Aging it is called after that paper) doesn't stand the test of time. Although i have seen him on Quora say that he is a little more confident about the %50 chance and even the %10 chance of not happening is closer to %5.
@TheSheekeyScienceShow
3 жыл бұрын
Thanks! Yeah, one thing i find fascinating is how physical forces e.g like tissues stiffness affect cellular signalling. I actually was doing a bit of a side project trying to understand how ot influences senescence but i use in vitro models which makes it harder to interpret and study since most protocols are based on using hard cell culture plates. Anyway, abandoned the project for now, but for sure is something that needs to be considered and hopefully better methods of testing them can be developed
@higreentj
3 жыл бұрын
Looks like everything is on track for ending aging by 2036. Drugs targeting telomerase to combat cancer looks like a possible cancer cure, and the vaccine against amyloid plaque is moving us closer to a cure for Alzheimers.
@darrenwalshe8513
3 жыл бұрын
@@higreentj amyloid protects the brain from inflammation
@higreentj
3 жыл бұрын
@@darrenwalshe8513 Genes that are beneficial when we are young become destructive as we age. Ending aging is a cure for Alzheimers and so many other disorders. We should aim for under thirty years of age as Africans have high blood pressure and diabetes in their mid to late thirties.
@davidwelburn5950
Жыл бұрын
@@higreentj That's very specific. If it does happen, will it help people who are already in their 70s, or is it too late by then?
@ssiddarth
3 жыл бұрын
Great video, glad to have found this channel & yes next video on Sheekey's theory of aging please 😬🤗
@JM-us3fr
3 жыл бұрын
The hallmarks have definitely helped me understand this stuff much better, but I’m just a mathematician and have no background in biology. None of that compares to how much better of a perspective I get when I watch your videos though!
@tomsport4537
3 жыл бұрын
Very interesting. Thank you so much!
@brewhog
3 жыл бұрын
Right on time! Thanks guys!
@lennihe
3 жыл бұрын
Wow, that's the third video released in one week! Just catching up here. I like the hallmarks of aging. For me, and I suspect a lot of other laymen, it broke through the misconception of aging as a linear process we are all going through at a more or less genetically predetermined rate. What's more exciting is the idea that we might be able to do something about it. That the hallmarks may not be accurate does not concern me that much. After all, isn't science the pursuit of being less wrong? One step at a time, then. Perfection remains forever beyond the horizon.
@ericrandolph7654
7 ай бұрын
Great presentation. López-Otín et al 2023 expands on the hallmarks of aging. I need to reread the original but I never considered the hallmarks a paradigm, more of a consensus. Like you said, a starting off point. Great job and great channel.
@Celtokee
3 жыл бұрын
Thank you, Sheekey, for aptly distinguishing the hallmarks of cancer from hallmarks of aging. Ms. Henrietta Lacks, the largest organism on planet Earth, would heartily agree with said distinction. Only thing missing in your brief but excellent overview--i.e., missing from the otherwise competent paradigms of de Gray and Sinclair-is that aging is fundamentally neither aberration nor an accumulation of errors, albeit accumulated errors is certainly a factor. By contrast, evolution from its very beginning was never about extending lifespan of individuals but rather upon maximizing biotic potential of a species. That is, to get as many of a particular species as possible to reproductive age. Period. End of story. That is “evolution” in a nutshell. Many cellular processes we are born with are evolved to help get us to reproductive age, after which age many of those same processes work against us, i.e., they cause what we term “aging.” Btw, with respect to evolution, regarding the theories of the honorable Gregor Mendel and Charles Darwin, it happens that I’ve staunchly argued since high school (in the 1960s) that canonical Mendelian and Darwinian mechanics cannot possibly explain evolution, cannot explain the explosion of biotic diversity, cannot explain the rapidity of adaptation to environmental change evidenced by the evolutionary record. That entire, tiresome meme of “adaptation to random errors in DNA” e.g. supposed random DNA errors caused by cosmic rays--never washed with me. I did the math. If evolution were a “response to random errors,” it would have taken not billions, not quadrillions, but rather quintillions of years. I’ve always argued that direct mechanisms of feedback from the environment to the genome must exist. Yes, I’m sorry, but I’m talking about long-pilloried Lamarkian mechanisms. Then, the explosion of understanding of epigenetics in the 1990s at long-last provided the missing evidence. For example, it has been demonstrated that repeated methylation of a gene causes a sequence change in that gene. I argue that that is a patently Lamarkian mechanism. Even if no one else does. Re: p53, you might find of passing interest my 2014 article, “Multiple Cytoproliferative Effects of Elevated Pyrimidines are DNA-Synthesis-Independent, and Include p53 Repression.”
@TheSheekeyScienceShow
3 жыл бұрын
Thanks! Is there a pdf you could send through, my uni doesnt grant me access to it? Also, you may find this recent article interesting, at least i did t.co/pDZOr8lOr8?amp=1
@Celtokee
3 жыл бұрын
@@TheSheekeyScienceShow You are welcome. I'm not sure how to send a pdf via youtube, but feel free to contact me via email: robertgipson@comcast.net and I'll send the pdf of my 2014 peer-reviewed article. Blessings 2 U, Sheekey.
@paulkabrna345
3 жыл бұрын
Paradigms are a solid foundation throughout the sciences. Where would we be without them. Mine is the Plate Tectonic paradigm :)
@titititi2022
3 жыл бұрын
After doing my personal reasearch on aging and trying many supplements that purported to halt and slow aging, I come to realize that most of them if not all are useless to say the least. It's probably because the aging field is in its infancy. Or maybe we will never get to know the real cause of aging as human organism is so complex and enigmatic. I find following the aging field is so frustrating as sometimes it's hard to differentiate between real scientists and fad scientists. Or even worse, sometimes those reputable scientists themselves get involved with brands of supplements in the shape of advisor or board member. I think all these things doesn't bode well with believability of aging field. Plus, the claims those supplement companies do is utter nonsence, clear lies as none of it came close to the expectation at least in my case.
@tomsport4537
3 жыл бұрын
I think you did‘t listen to her. You might have a completely wrong understanding of biology.
@AiternusCorp
3 жыл бұрын
I follow aging research closely and I generally agree
@Health.First.
3 жыл бұрын
I understand your points. Aging is a mess
@higreentj
3 жыл бұрын
SENS foundation see it as seven forms of damage and they have to be treated at the same time for reversal of aging to occur. They seem to be on track to ending aging in 2036.
@Patrick-bu5vy
3 жыл бұрын
Great work as always. I would be interested in seeing a video on why you think circadian rhythm disruption should be considered a hallmark of ageing. Keep up the good work.
@AyubKhan-el9kk
3 жыл бұрын
A timely reminder that we need a paradigm shift! The work over the past 30 years has been focused on the justification of individual markers and then attempting to cobble them together.... Not very smart! Humans are a complex organism, we follow a development pathway from birth and progress through distinct phases such as puberty etc... We have master regulators within systems such as the sympathetic, parasympathetic and endocrine systems which manage two way communications... Our longevity framework should primarily focus on strategies that extend the early adulthood phases and as secondary strategy use rejuvenation where early phases are past. For example strategies to minimise thymus gland entropy could have significant downstream impacts on organ vitality and is much more plausible than thymus regeneration at age 50 or 60. In a nutshell maintenance has a higher multiple than repair! Keep up the good work..
@livics610
3 жыл бұрын
How do you prevent the thymus atrophy?
@gkile6566
2 жыл бұрын
I appreciate your clear discussion of scientific paradigms, the distinction between hallmarks of cancer and hallmarks of aging makes sence but needs more exploration.
@BrentsTreehouse
3 жыл бұрын
Evolution does not create topologies. Human minds do. Natural emergence has complex interrelationships that surpasses our topological and paradigmatic thinking. AI may help us make sense.
@alwayslearning8365
3 жыл бұрын
Chances are the AI will use a paradigm to condense and hold the information in a form that can be interpreted and understood by humans. Humans love metafors and paradims are very similar to metafors.
@bennguyen1313
3 жыл бұрын
Regarding David Gems "The Hoverfly and the Wasp: A Critique of the Hallmarks of Aging as a Paradigm", and the more recent paper "The long lives of primates and the ‘invariant rate of ageing’ hypothesis" on I understand that aging involves hundreds of genes that get expressed differently throughout your life... however, repairing the normal cellular damage caused by living doesn't seem to rely on knowing exactly how the damage was caused. So would love to hear a friendly discussion on damage-repair vs epigenetics/methylation between Michael Rose (Hamilton Theory), Steven Austad , Joanna Mase, and Aubrey de Grey, David Sinclair, Nir Barzilai.. to determine what cellular damage is not in theory repairable. For example, Joanna suggests cells can either cooperate (which includes going silent/scenescent), or they become cancerous... if you try to undo scenescence, cancer will emerge!
@bennguyen1313
3 жыл бұрын
BTW, I recommend George Williams Reserve-Capacity-Hypothesis, that explains the antagonistic pleiotropy theory of aging . See Bret Weinstein's interview either on the Lex Fridman podcast (2h7m).. or on the Portal podcast (59m mark).
@markveen1373
3 жыл бұрын
My favorite hallmark of aging is "Luck". Dont think most people realise how many lotteries you need to win to be a supercentenarian. Even with the best genes. You would still be extremely fragile. Any fall, bacteria or virus could be the end long before you reach that point. And you probably dodged many bullets cell wise.
@ChessMasterNate
2 жыл бұрын
I had my own list I made in 2002. I called them "engines of aging"...but maybe that was overreach. Hallmarks, does not assume causation...merely accompaniment. I grouped things differently, and perhaps exaggerated the effects of hormones, and did not understand the significance of methylation at all. Other than that, it holds up reasonably. And perhaps we have neglected hormones a bit..given the thalamus regeneration stuff. My thinking has changed quite a bit, though. In the last year or two, I have been thinking more about reversing aging organ by organ, tissue by tissue, rather than assuming the things we do will just return everything to a youthful state. This, in part, was due to changes in my own health, where it appears my kidneys have reverted to a healthier state, my liver too, to some degree. And I have been impressed by the thalamus regeneration study. My brain has also improved in a few respects, and I have data going back 15 years or so. Over 200,000 data points AKA chess games ;) My biggest bone to pick with the “The hallmarks of aging” list is the omission of accumulations and damages to intercellular stuff. And not just the accumulations of cross-links and protein aggregations. I also think accumulation of pathogens has deleterious effects. So-called latent infections, likely are doing more damage than recognized by the anti-aging community. Toxins likely also accumulate that the kidneys and liver don't have a way to clear out. I think this may explain the plasma thinning positive effects in mouse studies. Then there is the accumulation of scar tissue, where repairs did not really restore function, it just plugged the holes. Some aging is more macro and less micro.
@unholyquail4560
3 жыл бұрын
Right now I am keeping to the Information theory of aging as main explanation, it explains the hallmarks but more and gives a better paradigm because it also shows how we should interpretate findings and explain them.
@AhmedAliNizamani
3 жыл бұрын
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@its1me1cal
3 жыл бұрын
Thank you, very thought-provoking
@MarmaladeINFP
3 жыл бұрын
The hallmarks of aging are probably not only similar to and overlapping with the hallmarks of cancer but probably also the hallmarks of inflammation, metabolic syndrome, hormonal dysfunction, autoimmune disorders, degenerative diseases, etc. Basically, the entire body is systems within systems. There are at least three connections between the gut and brain, one of which is direct. All of the body is interconnected. The hallmarks are simply ways for people to isolate mechanisms in ways that can be more easily observed, measured, and analyzed.
@livics610
3 жыл бұрын
Anyway, I think we age because life is based on Carbon, which is stable in binding with other molecules, but also pretty unstable. Maybe we just need Silicium mixed with Carbon to be more resilient... What about Thymus gland prevention of atrophy and what about Epitalon? What about diet? Which one is best for healthy longer life? Plant based with whole grains and legumes, or keto? Plus I.F. Plus what do you think of the Blue Zones? What about supplements or lifestyle for healthy prolonged lifespan?
@Sid-bc8pn
2 жыл бұрын
Great video as allways. But I am not so sure about the paradigm issue. Following the science about non linear systems, complexity and behavioral psychology there could also the opposite be true: Humans look for simple concepts and factors and this often stops or slows down their success (see Dietrich Dorner, "The logic of failure"). It is simple to stop a complex system with one factor (..e.g. with a vaccine) but it is not simple to stabilize or develop it. Of course you can always find simple words like "loss of information in the cells" or hallmark lists of symptoms (in a complex iterative system everything is a symptom) - but playing for example Conways simple "game of life" shows that success to "handle" complex systems is based on the opposite of a paradigm-evolution process. This may be the reason, why fast training in artificial neural networks starts to be more successful in understanding complex systems than we humans are..... perhaps it easier to stop aging if we do not try to find a simple theory first.
@monnoo8221
Жыл бұрын
Very nice presentation, indeed. well, they are called hallmarks. which is nothing else than downstream phenotypic classes, and as such they as categories to communicate between researchers. However, Grey's suggestions are a step back, because he talks about Causes", whether primary or secondary does not matter. A "claimed cause" is certainly a more restrictive basis for communication than a hallmark. The basic question though is NOT abut aging, or cancer, or p53, or PGs. It is quite important to identify the proper level of abstraction, and, as a researcher, to locate oneself within the edifice of layered abstractions. Kuhn is great, but did not go far enough in that direction. The basic question that would enable such a placement is, and each area of interest is marked by an enumeration: How (1) does it come (2) that a considerably large set (3) of biochemical reactions (4) produces (5) a dynamic body that is able to establish a self-generating (6) and self-maintaining (7) complexity (8)? This question is far more productive than asking "What is life?" And it is clear that (a) the question about life necessarily must be answered external to bio-chemistry, an (b) the question about aging is settling under the umbrella of the question proposed before. Without reference to the extra-biological schemes, research about aging (and cancer) will not make ground-braking progress. The paradigm of information certainly offers a promising horizon. You have already created a few episodes that are touching it. Yet, "information" is not very well understood by researchers in biology. Biology, eg of aging, is still conceptually very flat, and positivistic. It is largely unknown that research and biological systems unfold in a space of transcendental necessities, such as abstraction, generalization, associative storage of information. Mr. Goult seems to have developed a faint intuition what is lying ahead, but currently he still fails to get a grasp. Trying to address questions like aging from within bio-chemistry is like the gerbil that spins around in its little cage, because it developed a serious behavioral condition known as stereotype.
@jgarma
3 жыл бұрын
Eleanor, it would be useful to ascertain one primal cause of aging, which inevitably would have several downstream pathologically identifiable effects, but we’re not there yet. I agree with you that paradigms like the 9 “hallmarks” and de Grey’s 7 are useful, they don’t sufficiently tie things together, not only (in the hallmark’s case) the antagonistic/secondary and integrative/tertiary effects, but as you point out, the role of the microbiome and immunosupressants/inflammaging. Seems to me, from the perspective of aging interventions currently available to the public, we need to focus on nutrient cellular signaling; specifically, mTOR, AMPK and sirtuin pathways, as well as senescent cells. As you know, there are compounds that may be helpful with each of these.
@DessicatedCadaver
3 жыл бұрын
Famous quote: “ Nothing in biology makes sense, except in light of evolution.” Theodosius Dobzhansky All organisms, including the human, are a collection of adaptations to the environment . Aging must be seen in the light of evolution specific to homo sapiens. The paradigm of aging in humans flows entirely from that. In building such a paradigm, you must start with and continue with the evolutionary perspective.
@Earwaxfire909
3 жыл бұрын
What about protein glycosylations (advanced glycosylation end AGE products, and fetuin glycosylations)? Also what is the simplest way to monitor aging?
@johnvercellone1988
3 жыл бұрын
You are a very intelligent and talented person Dr Sheekey
@TheSheekeyScienceShow
3 жыл бұрын
Thanks but not a doctor.. At least not yet 😁
@altargull
3 жыл бұрын
New Paradigm called the Sheeky theory of aging. Put that in the history books everyone! It's settled.
@TheSheekeyScienceShow
3 жыл бұрын
Lol, well I hope it is *Sheekey, but we shall see
@siddoo6778
3 жыл бұрын
Do you think that the hallmarks of cancer might not be as genetically thorough as it could be? Would it be good enough to differentiate a premalignant lesion from cancer? I know that a lot of cancerous traits are seen in precancers, but the key differences are the types of mutated genes, e.g apc in a precancer, vs p53 in a putatively "true" cancer
@TheSheekeyScienceShow
3 жыл бұрын
For sure, i mean it was already updated once. But as an explanatory framework i think it still concurs much better with our current understanding than for aging. That said, the hallmarks of cancer is not something i think much about when doing my research, but i focus on the pre-neoplasia & senescence... So you make a very good point
@diamond_s
3 жыл бұрын
Don't the methylation clocks start from embryology and continue all throughout development and aging, and a good portion of these changes is also shared among multiple species? I think this points to programmed aging.
@rsberryalta
2 жыл бұрын
It would be interesting to see you approach the topic of the role of paradigms from the theory of knowledge advanced by David Deutsch, grounded in the ideas of Karl Popper. But another well done video!
@monnoo8221
Жыл бұрын
they have nothing to say here.... It would be detrimental for research taking those as guides
@SlamminGraham
3 жыл бұрын
Now watch as the field comes up with a much more abstract, complicated theory of aging, spends 30 years working with that model and doing experiments surrounding it, comes up with nothing useful, and then abandons it and comes all the way back to the Hallmarks. Meanwhile, we're all 30 years older and no closer to a cure for aging or age-related disease. It's happened plenty of times before in various scientific fields.
@rejuvenecer_atlas
3 жыл бұрын
👏👏👏👏👏👏👏👏👏👏I love your show!
@acousticmotorbike2118
2 жыл бұрын
Love your videos. Really useful.
@gravelman5789
3 жыл бұрын
as a Life Extender from 1982... i use Chronological Age/Physical Activity/Quality of Life as my metric. all this science stuff is good if you have the equipment, i do not. 😉
@neilchristensen538
3 жыл бұрын
Great video!
@Kreuzauge
3 жыл бұрын
The events of the last year and a half have caused me to question both the usefulness of scientific models, and the morals of the scientific community.
@AiternusCorp
3 жыл бұрын
Same
@livics610
3 жыл бұрын
Good luck being a conspirationist
@jefflittle8913
2 жыл бұрын
TLDR: ...and if you had trouble understanding all that, it is probably because we still don't really understand it either.
@norahlinehan4729
3 жыл бұрын
Can i ask...is it okay to take a multivitamin along with l carnitine, carnosine and berberine all at one meal. Would they be compatable with each other.
@robertsmyk4102
3 жыл бұрын
Is "aging" (frail and infirm) the next stage after maturing to adulthood or is there another stage as the baby grows past adulthood?
@littlevoice_11
3 жыл бұрын
What I find so confusing is the research on aging and how different macros accelerate particular markers. E.g. carbs for aging via inflammation and brain atrophy, protein (specifically igf1), now new research shows fats cause mitochondrial dysfunction and cancer metastasis. Research then shows that a combination of high fat and carbs is even worse. What is the optimal macro ratio? Over recent years I have believed a lower carb, high fat (from omega 3 and whole foods plants such as avocado, nuts, seeds, olives,cacao) with lots of colourful non starchy vegetables aiming for 35-50g fibre (without grains) and and plant based protein was best. Macros 25-30% protein 25% carbs 45%-50 fat. I'm moving beyond confused to feeling increasingly scared
@littlevoice_11
3 жыл бұрын
@@TheSheekeyScienceShow thank you. I think my worries stem from higher than desired hgA1c (5.7) despite being grain free and added sugar free. Also I feel better higher protein and higher fat but my blood urea has been high constantly in my life which makes me wonder... do I just have abnormal blood markers or is it diet driven. Doctors don't seem to advise on the matter nor do dieticians on the NHS.
@fennadikketetten1990
3 жыл бұрын
where in the UK specifically is your accent from?
@marcelotemer
3 жыл бұрын
In short: WFPB DIET
@livics610
3 жыл бұрын
Or keto? Or any diet with I.F.?
@elenatereshina7319
7 ай бұрын
Это старая статья. В этом году вышла новая.
@coffeeracer5777
2 жыл бұрын
Very interestig lecture, however please consider speaking in normal peace. It certainly would help in understanding the message.
@rui-9-cs315
3 жыл бұрын
❤️
@billirvine9078
3 жыл бұрын
systemic poisoning is a good fit.
@JBulsa
3 жыл бұрын
BNGO$
@tangan6228
3 жыл бұрын
Maybe switch to pyramid for a while, so we can see most to least.
@gravelman5789
3 жыл бұрын
as a Life Extender from 1982... i use Chronological Age/Physical Activity/Quality of Life as my metric. all this science stuff is good if you have the equipment, i do not. 😉
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