Aubrey de Grey originally defined what are now known as the “hallmarks of aging” as the SENS model in his book Ending Aging, published in September 2007, a full 6 years before the 2013 paper. Let’s give credit where credit is due. As someone who’s spoken out about academic integrity, I’m sure you can respect the need to tell the true story of the origins of this model.
Why do you believe that? Aubrey's seven types of damage are partially overlapping with the Hallmarks but are obviously not identical. I have no idea whether the authors of the Hallmarks paper were influenced by SENS or not. Despite what you may hear, the idea that damage causes aging or cataloging the types of damage associated with aging was going on far before Aubrey came along and many, many people contributed to that literature. SENS made the bold claim that fixing a small number of types of damage would essentially cure aging, which I disagreed with at the time and still disagree with. I'm not trying to minimize the role Aubrey played, but the Hallmarks paper has been much more influential within the field - both good and bad - than SENS. - MK
@@mkaeberlein I appreciate your candid response. The hallmarks do seem to me very much like a slightly modified and repackaged version of SENS, and almost no one outside of Aubrey was discussing this sort of model before 2013. Having said that, I obviously can't prove that SENS inspired the 2013 paper. It just seems to me that the SENS model gets far too little attention, and credit.
The hallmarks are useful signposts with our current understanding. Eventually I'd expect a very long list of hallmarks. What we need however is a much larger network analysis of the changes in biology during aging and a rigorous assessment of the association and casual relationships between the nodes of the network.
Hello, my question, that may sound naive, is why to use Rapamycin if the same effect of downregulate Mtor pathway and promote autophagy can be achieved by fasting ? Are we using an "external" tool (Rapamycin) where we already have a "natural" one (fasting)? EDIT: I found a possible answer from an article published on 2016 : The Journals of Gerontology: Series A, Volume 71, Issue 7, July 2016, Pages 866-875, In the abstract is reported the following sentence: "Rapamycin increased relative lean mass and decreased fat mass. IF [ Intermittent Fasting] failed to alter fat mass but lowered relative lean mass. Behaviorally, rapamycin resulted in high activity levels in old animals, IF increased levels of “anxiety” for both ages, and grip strength was not significantly altered by either treatment. Rapamycin, not IF, decreased circulating leptin in older animals to the level of young animals. Glucose levels were unchanged with age or treatment. Hypothalamic AMPK and pAMPK levels decreased in both older treated groups. This pattern of results suggests that rapamycin has more selective and healthspan-inducing effects when initiated late in life."
It's so good to see you with your own podcast! I've actually been referring to you on my Tik Tok. Hopefully you'll start posting your content over there as your grounded information is so needed to reach the masses. Funnily enough I was getting reported for misinformation especially re resveratrol and your views on this. I'd actually really love to hear what constitutes healthy/balanced nutrition and your thoughts on the extreme diets out there. I started extended water fasting and keto green as an extremely healthy person based on seeing 'experts' refer to this. I've been sick ever since but rarely see anyone warning extremely healthy people about these extremes. I now feel they're perhaps better suited for those who are obese or have type 2 diabetes and that it may be detrimental for extremely healthy people. For me, it at least contributed to my severe burnout. I literally love all of what you share! Thank you.
I like this concept that includes "connect" - simply because central nervous system involvement is seminal (and central) to biological processes. Furthermore, connection implies this interaction with the most critical aspect of the environment - the self and others.
Many have searched for ways to stay healthy and live longer. The results have been disappointing. What does work is don't do things that are bad for health. Avoid nutritional deficiencies. Stay active. Most medicines for healthy people to live longer did not really work. Many centenarians tell about their way to success, but it does not result in many people becoming centenarians with those methods. Maybe there are some exceptions: In Acciaroli there are a lot of centenarians who use rosemary. The Hunzas use apricot kernel oil (cyanide, senolytic?). In China Gynostemma pentaphyllum is used in an area where many centenarians live. Any thoughts about this?
So do we have any idea what instigates aging yet? What do these very long live species do different? Better genes? More copies of certain genes? Better epigentic regulation? 🤔
Limitations are wellcome, but being simple can make us to overlook details. On the contrary, simplicity may be the best tool leading truth (Feynmann inspiration😉)
Sounds like we are "looking for the keys under the light just because it's more convenient" with hallmarks. Similar problem is with mice studies vs humans, mice are more convenient, but good luck with translating. P.S. I prefer 12 pillars of the healthspan, because imo granularity adds clarity.
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Thank you Dr. Kaeberle for another great class! Looking forward to next episode. Can't wait to see where these courses will lead us.
Amazing lecture. So clear. Thank you!
Aubrey de Grey originally defined what are now known as the “hallmarks of aging” as the SENS model in his book Ending Aging, published in September 2007, a full 6 years before the 2013 paper.
Let’s give credit where credit is due. As someone who’s spoken out about academic integrity, I’m sure you can respect the need to tell the true story of the origins of this model.
Why do you believe that? Aubrey's seven types of damage are partially overlapping with the Hallmarks but are obviously not identical. I have no idea whether the authors of the Hallmarks paper were influenced by SENS or not. Despite what you may hear, the idea that damage causes aging or cataloging the types of damage associated with aging was going on far before Aubrey came along and many, many people contributed to that literature. SENS made the bold claim that fixing a small number of types of damage would essentially cure aging, which I disagreed with at the time and still disagree with. I'm not trying to minimize the role Aubrey played, but the Hallmarks paper has been much more influential within the field - both good and bad - than SENS. - MK
@@mkaeberlein I appreciate your candid response. The hallmarks do seem to me very much like a slightly modified and repackaged version of SENS, and almost no one outside of Aubrey was discussing this sort of model before 2013.
Having said that, I obviously can't prove that SENS inspired the 2013 paper. It just seems to me that the SENS model gets far too little attention, and credit.
The hallmarks are useful signposts with our current understanding. Eventually I'd expect a very long list of hallmarks. What we need however is a much larger network analysis of the changes in biology during aging and a rigorous assessment of the association and casual relationships between the nodes of the network.
Wow, we have alot to learn. Thanks for very informative lecture.✔💯
Hello, my question, that may sound naive, is why to use Rapamycin if the same effect of downregulate Mtor pathway and promote autophagy can be achieved by fasting ? Are we using an "external" tool (Rapamycin) where we already have a "natural" one (fasting)?
EDIT: I found a possible answer from an article published on 2016 : The Journals of Gerontology: Series A, Volume 71, Issue 7, July 2016, Pages 866-875,
In the abstract is reported the following sentence:
"Rapamycin increased relative lean mass and decreased fat mass. IF [ Intermittent Fasting] failed to alter fat mass but lowered relative lean mass. Behaviorally, rapamycin resulted in high activity levels in old animals, IF increased levels of “anxiety” for both ages, and grip strength was not significantly altered by either treatment. Rapamycin, not IF, decreased circulating leptin in older animals to the level of young animals. Glucose levels were unchanged with age or treatment. Hypothalamic AMPK and pAMPK levels decreased in both older treated groups. This pattern of results suggests that rapamycin has more selective and healthspan-inducing effects when initiated late in life."
Wow you rocketing fast to 3k subscriber
It's so good to see you with your own podcast! I've actually been referring to you on my Tik Tok. Hopefully you'll start posting your content over there as your grounded information is so needed to reach the masses. Funnily enough I was getting reported for misinformation especially re resveratrol and your views on this. I'd actually really love to hear what constitutes healthy/balanced nutrition and your thoughts on the extreme diets out there. I started extended water fasting and keto green as an extremely healthy person based on seeing 'experts' refer to this. I've been sick ever since but rarely see anyone warning extremely healthy people about these extremes. I now feel they're perhaps better suited for those who are obese or have type 2 diabetes and that it may be detrimental for extremely healthy people. For me, it at least contributed to my severe burnout. I literally love all of what you share! Thank you.
I like this concept that includes "connect" - simply because central nervous system involvement is seminal (and central) to biological processes. Furthermore, connection implies this interaction with the most critical aspect of the environment - the self and others.
Pragmatic and logical.
The hallmarks of ageing are fascinating.I read the paper by Lopez truly eye opening.
Many have searched for ways to stay healthy and live longer. The results have been disappointing. What does work is don't do things that are bad for health. Avoid nutritional deficiencies. Stay active. Most medicines for healthy people to live longer did not really work. Many centenarians tell about their way to success, but it does not result in many people becoming centenarians with those methods.
Maybe there are some exceptions: In Acciaroli there are a lot of centenarians who use rosemary.
The Hunzas use apricot kernel oil (cyanide, senolytic?).
In China Gynostemma pentaphyllum is used in an area where many centenarians live.
Any thoughts about this?
So do we have any idea what instigates aging yet? What do these very long live species do different? Better genes? More copies of certain genes? Better epigentic regulation? 🤔
In 500BCE they already know that the earth is a sphere. And a in 1500BCE too and fore sure before.
Limitations are wellcome, but being simple can make us to overlook details. On the contrary, simplicity may be the best tool leading truth (Feynmann inspiration😉)
Wouldn't eating overlap dysregulated nutrient sensing?
Sounds like we are "looking for the keys under the light just because it's more convenient" with hallmarks.
Similar problem is with mice studies vs humans, mice are more convenient, but good luck with translating.
P.S. I prefer 12 pillars of the healthspan, because imo granularity adds clarity.