5 ms·

We are living in the midst of the early phases of a biotechnology revolution every bit as profound and transformative as the computing revolution from the 1970s

We are living in the midst of the early phases of a biotechnology revolution every bit as profound and transformative as the computing revolution from the 1970s on. It is less apparent than it might be to the average person in the street because (a) next to no-one really spends much time thinking about medical research unless they have to, which is a whole massive issue with our society in and of itself, (b) regulatory burdens on medical technology ensures that the clinic is 10-20 years behind the bounds of the possible in the labs. Medical tourism does its part to help keep that delay lower than it might, but it's still a huge burden, and a huge cost in life - especially now that the upward curve of progress is potentially so steep. The potential to be able to treat aging and begin to bring it under medical control within the next 20 years - IF the right research fields begin to dominate the mainstream, IF the funding arises, IF the public wakes up and regards aging research in the same was as they regard cancer research - is very real. That is why people like me spend time and effort to bang the drum, conduct grassroots fundraisers, and support progress in SENS-like rejuvenation research focused on repair of the cellular and tissue damage thought to cause aging. For example, clearance of senescent cells, an approach which has just now reached the point of credible demonstrations in normal mice, but needs much more support to make it into the mainstream. Is Calico funding this? No, not yet, and they won't until it gets more support: http://www.scripps.edu/news/press/2015/20150309agingcell.html http://www.scripps.edu/news/press/2015/20150309agingcell.htm... Advocates and the research community are making progress, great progress when you look at 2015 in comparison to the state of things in 2005, but we need more people to take the step, become philanthropists, and materially support this and other early-stage research with the aim of bringing medicine under medical control. That support really does make a difference.

farresito 11y ago
Thank you for your answer and for supporting this research! I know it's very hard to do, especially with things in such a young state, but do you think you could provide any more information of where we might be in 10, 20 or 50 years?
- reasonattlm 11y ago
  My takes: ---------- How long until life-extending medical therapies are developed? How long is a piece of string? Questions of time depend on questions of money. Over the past decade the rough estimates for a fully funded crash research program to realize SENS in mice as rapidly as possible have floated around $1-2 billion over ten to twenty years. It might cost less than that now, given the rapid advance of biotechnology, but not enormously less. Unfortunately SENS is nowhere near as well funded as this: the current budget for the SENS Research Foundation has only recently reached $5 million / year. So it will certainly take time to increase funding to the optimal levels of $100 million / year or more; this is a major undertaking involving the creation of many new major programs of medical research throughout the world. That in and of itself might require decades, and it is hard to estimate the pace of growth in the early stages of a new industry. Any number of small, happenstance choices made by today's investors and researchers might gain or lose years of future progress. Meanwhile on the other side of the fence drug discovery programs are undertaken in search of ways to modestly slow aging. We know that it can take a decade and $1 billion to push a good drug candidate through validation and regulatory hurdles, all the way from early tests to clinical use. There are no good candidates at this time, but every sign that some may emerge in the next few years based on analogs to rapamycin. So it's not unreasonable to think that a first generation drug that might slightly slow aging in humans could emerge in the mid to late 2020s. Even at that point the research community may not be able to say whether it in fact actually slows aging in humans, however, versus definitively knowing that it produces positive changes in short-term measures of health. ----------
- reasonattlm 11y ago
  A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field. While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering: 1) Destruction of Senescent Cells Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features. The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism. 2) Selective Pruning and Support of the Immune System One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule. Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient's immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells - or more adventurous processes such as cultivating thymic cells in a patient's lymph nodes. 3) Mitochondrial Repair Our mitochondria sabotage us. There's a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems. There are any number of proposed methods for dealing with this component of the aging process - either repairing or making it irrelevant - and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrary therapies to the interior or mitochondria. It all looks very promising. Further, the study of mitochondria is very broad and energetic, and has a strong presence in many areas of medicine and life science research. While few groups in the field are currently engaged in work on mitochondrial repair, there is an enormous reservoir of potential funding and workers awaiting any method of repair shown to produce solid results.
xaa 11y ago
Does SENS get NIA funding? Have they put forward any candidates to NIA's ITP?
- reasonattlm 11y ago
  SENS and SENS-like work outside the area of cancer and stem cell research is generally at the pre-animal-testing stage, so not something you can run via the ITP. Senescent cell clearance is there, so could be making in that direction in the years ahead. Nothing moves fast of course. I'm not sure where the ITP stands on things like stem cell treatments. They are very focused on diet, drugs, supplements, and resulting complex changes in the operation of normal metabolism. i.e. things that don't matter if you want meaningful results in extended healthy life. Good for scientific rigor though, going back through all the studies in the past that failed to control for inadvertent calorie restriction and showing that they were wrong.
  - xaa 11y ago
    Well, they don't allow interventions that require daily injections, etc, but the implication seems to be that something that requires a once-a-month injection, such as senescent cell clearance, would likely be allowed. Some of the "senolytics" are small molecules as well (Jim Kirkland's work, for example). Actually the ITP is not just interested in metabolism. They do hormones and anti-inflammatories as well. But I don't get the impression that they're solely focused on those things: anyone who can make a good case for a non-labor-intensive intervention can get in. That's why I asked if SENS has applied to the ITP: because I know they have some different ideas than academia, but I'd like to know more about specific interventions they've proposed or tested. Are you by chance going to the AAA meeting in Marina del Rey in a few weeks? I'd buy you a beer there and we could continue the conversation then ;)

farresito 11y ago

Thank you for your answer and for supporting this research! I know it's very hard to do, especially with things in such a young state, but do you think you could provide any more information of where we might be in 10, 20 or 50 years?

reasonattlm 11y ago
My takes: ---------- How long until life-extending medical therapies are developed? How long is a piece of string? Questions of time depend on questions of money. Over the past decade the rough estimates for a fully funded crash research program to realize SENS in mice as rapidly as possible have floated around $1-2 billion over ten to twenty years. It might cost less than that now, given the rapid advance of biotechnology, but not enormously less. Unfortunately SENS is nowhere near as well funded as this: the current budget for the SENS Research Foundation has only recently reached $5 million / year. So it will certainly take time to increase funding to the optimal levels of $100 million / year or more; this is a major undertaking involving the creation of many new major programs of medical research throughout the world. That in and of itself might require decades, and it is hard to estimate the pace of growth in the early stages of a new industry. Any number of small, happenstance choices made by today's investors and researchers might gain or lose years of future progress. Meanwhile on the other side of the fence drug discovery programs are undertaken in search of ways to modestly slow aging. We know that it can take a decade and $1 billion to push a good drug candidate through validation and regulatory hurdles, all the way from early tests to clinical use. There are no good candidates at this time, but every sign that some may emerge in the next few years based on analogs to rapamycin. So it's not unreasonable to think that a first generation drug that might slightly slow aging in humans could emerge in the mid to late 2020s. Even at that point the research community may not be able to say whether it in fact actually slows aging in humans, however, versus definitively knowing that it produces positive changes in short-term measures of health. ----------
reasonattlm 11y ago
A toolkit for producing true rejuvenation in humans will require a range of different therapies, each of which can repair or reverse one of the varied root causes of degenerative aging. Research is underway for all of these classes of therapy, but very slowly and with very little funding in some cases. The funding situation spans the gamut from that of the stem cell research community, where researchers are afloat in money and interest, to the search for ways to break down advanced glycation endproducts (AGEs), which is a funding desert by comparison, little known or appreciated outside the small scientific community that works in that field. While bearing in mind that progress in projects with little funding is unpredictable in comparison to that of well-funded projects, I think that we can still take a stab at a likely order of arrival for various important therapies needed to reverse aging. Thus an incomplete list follows, running from the earliest to the latest arrival, with the caveat that it is based on the present funding and publicity situation. If any one of the weakly funded and unappreciated lines of research suddenly became popular and awash with resources, it would probably move up in the ordering: 1) Destruction of Senescent Cells Destroying specific cells without harming surrounding cells is a well-funded line of research thanks to the cancer community, and the technology platforms under development can be adapted to target any type of cell once it is understood how to target its distinctive features. The research community has already demonstrated benefits from senescent cell destruction, and there are research groups working on this problem from a number of angles. A method of targeting senescent cells for destruction was recently published, and we can expect to see more diverse attempts at this in the next few years. As soon as one of these can be shown to produce benefits in mice that are similar to the early demonstrations, then senescent cell clearance becomes a going concern: something to be lifted from the deadlocked US regulatory process and hopefully developed quickly into a therapy in Asia, accessed via medical tourism. 2) Selective Pruning and Support of the Immune System One of the reasons for immune system decline is crowding out of useful immune cells by memory immune cells that serve little useful purpose. Here, targeted cell destruction can also produce benefits, and early technology demonstrations support this view. Again, the vital component is the array of mechanisms needed to target the various forms of immune cell that must be pruned. I expect the same rising tide of technology and knowledge that enables senescent cell targeting will lead to the arrival of immune cell targeting on much the same schedule. Culling the immune system will likely have to be supported with some form of repopulation of cells. It is already possible to repopulate a patient's immune system with immune cells cultivated from their own tissues, as demonstrated by the limited number of full immune system reboots carried out to cure autoimmune disorders. Alternatives to this process include some form of tissue engineering to recreate the dynamic, youthful thymus as a source of immune cells - or more adventurous processes such as cultivating thymic cells in a patient's lymph nodes. 3) Mitochondrial Repair Our mitochondria sabotage us. There's a flaw in their structure and operation that causes a small but steadily increasing fraction of our cells to descend into a malfunctioning state that is destructive to bodily tissues and systems. There are any number of proposed methods for dealing with this component of the aging process - either repairing or making it irrelevant - and a couple are in that precarious state of being just a little more solidity and work away from the point at which they could begin clinical development. The diversity of potential approaches in increasing too. Practical methods are now showing up for ways to put new mitochondria into cells, or target arbitrary therapies to the interior or mitochondria. It all looks very promising. Further, the study of mitochondria is very broad and energetic, and has a strong presence in many areas of medicine and life science research. While few groups in the field are currently engaged in work on mitochondrial repair, there is an enormous reservoir of potential funding and workers awaiting any method of repair shown to produce solid results.

xaa 11y ago

Does SENS get NIA funding? Have they put forward any candidates to NIA's ITP?

reasonattlm 11y ago
SENS and SENS-like work outside the area of cancer and stem cell research is generally at the pre-animal-testing stage, so not something you can run via the ITP. Senescent cell clearance is there, so could be making in that direction in the years ahead. Nothing moves fast of course. I'm not sure where the ITP stands on things like stem cell treatments. They are very focused on diet, drugs, supplements, and resulting complex changes in the operation of normal metabolism. i.e. things that don't matter if you want meaningful results in extended healthy life. Good for scientific rigor though, going back through all the studies in the past that failed to control for inadvertent calorie restriction and showing that they were wrong.
- xaa 11y ago
  Well, they don't allow interventions that require daily injections, etc, but the implication seems to be that something that requires a once-a-month injection, such as senescent cell clearance, would likely be allowed. Some of the "senolytics" are small molecules as well (Jim Kirkland's work, for example). Actually the ITP is not just interested in metabolism. They do hormones and anti-inflammatories as well. But I don't get the impression that they're solely focused on those things: anyone who can make a good case for a non-labor-intensive intervention can get in. That's why I asked if SENS has applied to the ITP: because I know they have some different ideas than academia, but I'd like to know more about specific interventions they've proposed or tested. Are you by chance going to the AAA meeting in Marina del Rey in a few weeks? I'd buy you a beer there and we could continue the conversation then ;)