Great post, Dan! Thanks for taking on Dr. Coughlin. Sadly, he isn't alone. Rahm Emanuel's brother Ezekiel is a self-proclaimed bioethicist who wrote a now-famous article for the Atlantic called "Why I Hope to Die at 75" (https://www.theatlantic.com/magazine/archive/2014/10/why-i-hope-to-die-at-75/379329/). I thought that article was the pinnacle of irrationality, but Coughlin's bizarre view is a contender. And this view is sadly true of other biomedical fields where problems are hard and people are failing to solve them. This attitude of "don't cure, destigmatize" is also becoming popular in regard to mental diseases and disorders. The biomedical sciences have fared so poorly in treating mental illnesses that it has become trendy to accuse scientists of "medicalizing" mental illness, and to promote destigmatization (rather than cure) of even serious mental dysfunction.
Hey Preston, great to have you here and thank you for the very interesting comments.
Regarding Ezekiel Emanuel, I have no problem with anyone who wishes to forgo longevity treatments. I just ask that they respect the fact that many people do want to live longer and they recognize that longevity biomedicine can massively reduce healthcare expenditures (something Emanuel seems completely blind to). Emanuel has suggested that many people over age 75 have lives that are no longer worth living. I don't think you can get more ageist than that. His outlook is also profoundly pessimistic and cynical. If everyone adopted his attitude medical progress would come screeching to a halt.
You make an excellent point about mental health conditions. When writing this article I was reminded of the "Hearing Voices" movement which basically says "actually having schizophrenia is always perfectly OK for both the individual and society".
Addressing the unfair bias and discrimination and raising awareness about (and addressing) important health issues are not mutually exclusive!
When Emanuel wrote this piece he was 56 yo. The average life expectancy of a 55 yo (LE55) in his demographic (college educated, white, male, etc.), is about another 27 years (about 82 years total). It is especially bizarre to desire to be less than average for the most essential feature and function of a living organism--life itself! Many people live to well over 90, and when these healthy, slowly aging people are 75 yo they are living full and meaningful lives. Hans Bethe was still publishing when he was over 90, and last I heard, Jack Strominger is still running his research lab at Harvard at age 97. Why not aspire to be above average in length of life and fulfillment? One can only conclude that despite his college education, his study of bioethics as a career, and other advantages of his circumstances, Emanuel simply has no idea what he is talking about.
Thank you for writing this and the extensive discussion. It is sad to see folks succumb to what I would call the “easy niche” allure. That’s a growing niche these days, telling folks stories they’d like to hear ... I could go on about this. Aging is real... talk to serious folks experiencing aging. Can we do better in extending what Sinclair and others call ‘youthspan’? Sure. Real world data suggests there are adaptations to be had... yes, accumulating genetic errors & decay of organ function efficiency are real.
Thank you for the comment Elan! I agree. Sadly people just want to hear about how people are living healthy into old age, and turn away from looking at the suffering going on. So, people like Coughlin with polyannish views on aging are celebrated while those speaking up about all of the suffering and problems of aging are seen as cranky "complainers" and looked down upon, shunned, and ignored.
Reviewing the Substack again. A) aging IS very real, being in my seventies I can attest to it, and identify specific changes B) aging can be stopped C) aged cells can be replaced in most cases D) the challenges are with post-mitotic cells (neurons and cardiomyocytes) these are terminally differentiated meaning most of them if not all, are those you’re born with; other cells regenerate frequently (timescales from days to a few years) neurons are the most challenging to lose. Every neuron lost changes the network it was part of (neurons connected to thousands to tens of thousands of other neurons) with enough neurons lost to a network, that network fails. I don’t know what the reserve capacity is; we know physiologically that as we age reserve capacity declines so we can’t place extra demands later in life , that one can earlier in life. I’m fully convinced THERE are ways to stop aging and actually substantially increase lifespan (there are animals that live hundreds of years and trees that live thousands of years). I’m researching this. My conclusions are that the talent required to make real progress is absent from the field. I believe also AI can help. The problem will be cracked within 20-40 years (maybe earlier with the right talent and AI); the question then will of course be: who will get access to much longer lifespan
Thanks Elan! Look into the work of Jean Hebert on literally replacing lost or aging neurons with fresh stem cells! Expensive and radical but a possible path forward…
ok, just checked (courtesy of Gemini) - Hébert acknowledges that you cannot swap out large sections of the brain at once without destroying an individual's memories, skills, and self-identity. Instead, his strategy proposes replacing the neocortex progressively over years in tiny, localized micro-sections (Hébert & Vijg, 2018).
By replacing only a fraction of a percent of the neocortex at any given time, the brain can utilize its inherent neuroplasticity. The surrounding, older neural networks are given enough time to train the newly introduced tissue, gradually transferring encoded information and functional responsibilities to the fresh cells before the next adjacent micro-patch is replaced (Hébert, 2022).
Dan, I will, thanks for the reference. The real issue with the lost neurons is the loss of experience accumulated over long periods of time; that experience is encoded in the connections already established and operating Hebbs rule (neurons that fire together wire together), so the new neurons can support new learning, which is great, but they can't mitigate lost connections and change of network topology. I am actually spending a considerable amount of time researching this (and have been doing so for a while ... part of the real challenge is how to capture /maintain / transfer knowledge that's been accumulated. One of the questions that pops up with 'fresh new neurons', that i hadn't considered, but now noted for exploration, can a network of neurons train a new neuron to maintain a robust network, if so, that would be wonderful.
Great post, Dan! Thanks for taking on Dr. Coughlin. Sadly, he isn't alone. Rahm Emanuel's brother Ezekiel is a self-proclaimed bioethicist who wrote a now-famous article for the Atlantic called "Why I Hope to Die at 75" (https://www.theatlantic.com/magazine/archive/2014/10/why-i-hope-to-die-at-75/379329/). I thought that article was the pinnacle of irrationality, but Coughlin's bizarre view is a contender. And this view is sadly true of other biomedical fields where problems are hard and people are failing to solve them. This attitude of "don't cure, destigmatize" is also becoming popular in regard to mental diseases and disorders. The biomedical sciences have fared so poorly in treating mental illnesses that it has become trendy to accuse scientists of "medicalizing" mental illness, and to promote destigmatization (rather than cure) of even serious mental dysfunction.
Hey Preston, great to have you here and thank you for the very interesting comments.
Regarding Ezekiel Emanuel, I have no problem with anyone who wishes to forgo longevity treatments. I just ask that they respect the fact that many people do want to live longer and they recognize that longevity biomedicine can massively reduce healthcare expenditures (something Emanuel seems completely blind to). Emanuel has suggested that many people over age 75 have lives that are no longer worth living. I don't think you can get more ageist than that. His outlook is also profoundly pessimistic and cynical. If everyone adopted his attitude medical progress would come screeching to a halt.
You make an excellent point about mental health conditions. When writing this article I was reminded of the "Hearing Voices" movement which basically says "actually having schizophrenia is always perfectly OK for both the individual and society".
Addressing the unfair bias and discrimination and raising awareness about (and addressing) important health issues are not mutually exclusive!
When Emanuel wrote this piece he was 56 yo. The average life expectancy of a 55 yo (LE55) in his demographic (college educated, white, male, etc.), is about another 27 years (about 82 years total). It is especially bizarre to desire to be less than average for the most essential feature and function of a living organism--life itself! Many people live to well over 90, and when these healthy, slowly aging people are 75 yo they are living full and meaningful lives. Hans Bethe was still publishing when he was over 90, and last I heard, Jack Strominger is still running his research lab at Harvard at age 97. Why not aspire to be above average in length of life and fulfillment? One can only conclude that despite his college education, his study of bioethics as a career, and other advantages of his circumstances, Emanuel simply has no idea what he is talking about.
Yes, or he's dealing with at least mild mental illness quite frankly.
Thank you for writing this and the extensive discussion. It is sad to see folks succumb to what I would call the “easy niche” allure. That’s a growing niche these days, telling folks stories they’d like to hear ... I could go on about this. Aging is real... talk to serious folks experiencing aging. Can we do better in extending what Sinclair and others call ‘youthspan’? Sure. Real world data suggests there are adaptations to be had... yes, accumulating genetic errors & decay of organ function efficiency are real.
Thank you for the comment Elan! I agree. Sadly people just want to hear about how people are living healthy into old age, and turn away from looking at the suffering going on. So, people like Coughlin with polyannish views on aging are celebrated while those speaking up about all of the suffering and problems of aging are seen as cranky "complainers" and looked down upon, shunned, and ignored.
Reviewing the Substack again. A) aging IS very real, being in my seventies I can attest to it, and identify specific changes B) aging can be stopped C) aged cells can be replaced in most cases D) the challenges are with post-mitotic cells (neurons and cardiomyocytes) these are terminally differentiated meaning most of them if not all, are those you’re born with; other cells regenerate frequently (timescales from days to a few years) neurons are the most challenging to lose. Every neuron lost changes the network it was part of (neurons connected to thousands to tens of thousands of other neurons) with enough neurons lost to a network, that network fails. I don’t know what the reserve capacity is; we know physiologically that as we age reserve capacity declines so we can’t place extra demands later in life , that one can earlier in life. I’m fully convinced THERE are ways to stop aging and actually substantially increase lifespan (there are animals that live hundreds of years and trees that live thousands of years). I’m researching this. My conclusions are that the talent required to make real progress is absent from the field. I believe also AI can help. The problem will be cracked within 20-40 years (maybe earlier with the right talent and AI); the question then will of course be: who will get access to much longer lifespan
Thanks Elan! Look into the work of Jean Hebert on literally replacing lost or aging neurons with fresh stem cells! Expensive and radical but a possible path forward…
ok, just checked (courtesy of Gemini) - Hébert acknowledges that you cannot swap out large sections of the brain at once without destroying an individual's memories, skills, and self-identity. Instead, his strategy proposes replacing the neocortex progressively over years in tiny, localized micro-sections (Hébert & Vijg, 2018).
By replacing only a fraction of a percent of the neocortex at any given time, the brain can utilize its inherent neuroplasticity. The surrounding, older neural networks are given enough time to train the newly introduced tissue, gradually transferring encoded information and functional responsibilities to the fresh cells before the next adjacent micro-patch is replaced (Hébert, 2022).
Dan, I will, thanks for the reference. The real issue with the lost neurons is the loss of experience accumulated over long periods of time; that experience is encoded in the connections already established and operating Hebbs rule (neurons that fire together wire together), so the new neurons can support new learning, which is great, but they can't mitigate lost connections and change of network topology. I am actually spending a considerable amount of time researching this (and have been doing so for a while ... part of the real challenge is how to capture /maintain / transfer knowledge that's been accumulated. One of the questions that pops up with 'fresh new neurons', that i hadn't considered, but now noted for exploration, can a network of neurons train a new neuron to maintain a robust network, if so, that would be wonderful.
Aging deniers are as obviously deluded as, for example, climate change deniers, and potentially as dangerous.