Nice piece Emanuele, I felt that I actually got what LEV was and why we should aim to get there more after reading this post than I did after reading your previous ones. A general comment is that from what the Lifespan.io roadmap shows, it really seems like anti-aging research has progressed quite far (i.e. quite a few on going and some late-stage clinical trials) relative to the fields fringe nature and apparently limited funding.
In terms of questions, there is one thing that I think is fairly critical—how well do multiple interventions combine?
What SRF claims is that solving all the seven categories will probably lead to lifespans longer than the current maximum.
As I understand this, treatments for all of the categories are being developed in independently. Is anybody looking to see if they can all be used in parallel? Could there be interactions between treatments that prevent this? It seems that the expected value of the anti-aging research is only realised if it will, at some point, be possible to treat all the categories in parallel. Research into a treatment for one category that wouldn’t be compatible with other treatments seems like it should receive much lower priority.
It seems like there could be ways to test this already. For instance, the roadmap shows many treatments are already at the pre-clinical in-vivo stage. If we start applying multiple therapies in-vivo, we can start to test how compatible they are. Do you know if that has been done?
Starting to test multiple therapies in-vivo could also provide some fundamental evidence about how the benefits of multiple therapies combine. At the moment the assumption seems to be that, say, individually treating mitochondrial mutations and extracellular aggregates, prolongs expected life by X and Y years, respectively, so treating them both in combination will prolong life by X + Y years, but both negative or positive returns on the combination could occur. To be honest, I have some general scepticism about anti-aging research because ageing is very widely conserved in the animal kingdom (there are only a few animals with negligible senescence). It could be that there is some evolutionary path way negligible senescent animals went down that is hard to cross-over to even if we treat all the categories, so I have a weak prior that senescent animals will get diminishing returns from multiple therapies.
Another point that I think is worth discussing is how the damage repair approach effects the metabolic processes causing the damage?
Dr. de Grey always stresses how the damage repair approach, which he also calls “the maintenance approach”, has a big advantage over geriatrics and the kind of biogerontology aimed at targeting the metabolic processes that are causing this damage.
For instance, if we treat an 80 year olds telomere attrition, are we going to need to treat them again in the future? Are consecutive treatments going to need to occur at more regular intervals? I don’t know much about how treatments effect the underlying metabolic processes (as noted, metabolism is very complicated), but it could be that these continue picking up pace even as the damage they cause is repaired. Knowing about this could also be important in assessing the value of LEV as a whole, particularly if treatments have dose dependent side-effects. For instance, it may be that we can treat ageing out to 200 or so, but then rate of damage is so high that treatment dose required is too strong to tolerate. This is probably an issue for SENS 2.0, but it also seems like an area where some in-vivo testing can provide some useful information. If nothing else, finding that regularity of therapy is expected to increases suggests that treatments with more tolerable side-effects might be preferred (where there is a choice).
This are both fairly technical issues compared to the other questions you proposed in the post, but I think they point towards some fairly crucial considerations about how the additivity and repeatability of therapies will effect the goal of LEV.
Thanks Gavin, there are some great questions in here.
I’m only able to answer two of them pretty conclusively:
For instance, if we treat an 80 year olds telomere attrition, are we going to need to treat them again in the future? Are consecutive treatments going to need to occur at more regular intervals?
The answer is simply: absolutely, yes.
If you condense the most crucial questions I will add them in the interview, and we will see what Aubrey de Grey has to say.
-Of the treatments currently being developed (in reference to the list on lifespan.io), is it likely that treatments for multiple hallmarks can be used in parallel?
--Are there currently any observed or expected interactions between different treatments?
--Has any effort been made to see if the effects of multiple treatment are additive, in terms of improved lifespan, in a pre-clinical study?
-What side effects have been observed for the treatments currently in clinical trials?
It’s interesting to know that recurring and more frequent treatments are going to be needed. That point hasn’t been obvious to me before, but it could be important to consider in relation to the economics of scaling up mass anti-aging treatment—it’s not like a one of vaccination against a specific type of ageing damage, but still a ‘condition’ that requires ongoing, and perhaps increasing, care.
You are correct. I will also add a question about how much time he estimates will need to pass between one treatment and its repetition. This could be fairly calculable from the informations the scientific community already has (the rate of damage in the elderly). I will get back to you with another reply in case I come up with other questions in light of your comment and if I modify or add something to your questions.
Nice piece Emanuele, I felt that I actually got what LEV was and why we should aim to get there more after reading this post than I did after reading your previous ones. A general comment is that from what the Lifespan.io roadmap shows, it really seems like anti-aging research has progressed quite far (i.e. quite a few on going and some late-stage clinical trials) relative to the fields fringe nature and apparently limited funding.
In terms of questions, there is one thing that I think is fairly critical—how well do multiple interventions combine?
As I understand this, treatments for all of the categories are being developed in independently. Is anybody looking to see if they can all be used in parallel? Could there be interactions between treatments that prevent this? It seems that the expected value of the anti-aging research is only realised if it will, at some point, be possible to treat all the categories in parallel. Research into a treatment for one category that wouldn’t be compatible with other treatments seems like it should receive much lower priority.
It seems like there could be ways to test this already. For instance, the roadmap shows many treatments are already at the pre-clinical in-vivo stage. If we start applying multiple therapies in-vivo, we can start to test how compatible they are. Do you know if that has been done?
Starting to test multiple therapies in-vivo could also provide some fundamental evidence about how the benefits of multiple therapies combine. At the moment the assumption seems to be that, say, individually treating mitochondrial mutations and extracellular aggregates, prolongs expected life by X and Y years, respectively, so treating them both in combination will prolong life by X + Y years, but both negative or positive returns on the combination could occur. To be honest, I have some general scepticism about anti-aging research because ageing is very widely conserved in the animal kingdom (there are only a few animals with negligible senescence). It could be that there is some evolutionary path way negligible senescent animals went down that is hard to cross-over to even if we treat all the categories, so I have a weak prior that senescent animals will get diminishing returns from multiple therapies.
Another point that I think is worth discussing is how the damage repair approach effects the metabolic processes causing the damage?
For instance, if we treat an 80 year olds telomere attrition, are we going to need to treat them again in the future? Are consecutive treatments going to need to occur at more regular intervals? I don’t know much about how treatments effect the underlying metabolic processes (as noted, metabolism is very complicated), but it could be that these continue picking up pace even as the damage they cause is repaired. Knowing about this could also be important in assessing the value of LEV as a whole, particularly if treatments have dose dependent side-effects. For instance, it may be that we can treat ageing out to 200 or so, but then rate of damage is so high that treatment dose required is too strong to tolerate. This is probably an issue for SENS 2.0, but it also seems like an area where some in-vivo testing can provide some useful information. If nothing else, finding that regularity of therapy is expected to increases suggests that treatments with more tolerable side-effects might be preferred (where there is a choice).
This are both fairly technical issues compared to the other questions you proposed in the post, but I think they point towards some fairly crucial considerations about how the additivity and repeatability of therapies will effect the goal of LEV.
Thanks Gavin, there are some great questions in here.
I’m only able to answer two of them pretty conclusively:
The answer is simply: absolutely, yes.
If you condense the most crucial questions I will add them in the interview, and we will see what Aubrey de Grey has to say.
Sure, I think the key questions would be:
-Of the treatments currently being developed (in reference to the list on lifespan.io), is it likely that treatments for multiple hallmarks can be used in parallel?
--Are there currently any observed or expected interactions between different treatments?
--Has any effort been made to see if the effects of multiple treatment are additive, in terms of improved lifespan, in a pre-clinical study?
-What side effects have been observed for the treatments currently in clinical trials?
It’s interesting to know that recurring and more frequent treatments are going to be needed. That point hasn’t been obvious to me before, but it could be important to consider in relation to the economics of scaling up mass anti-aging treatment—it’s not like a one of vaccination against a specific type of ageing damage, but still a ‘condition’ that requires ongoing, and perhaps increasing, care.
You are correct. I will also add a question about how much time he estimates will need to pass between one treatment and its repetition. This could be fairly calculable from the informations the scientific community already has (the rate of damage in the elderly). I will get back to you with another reply in case I come up with other questions in light of your comment and if I modify or add something to your questions.