6 ms·

Safe, yes, but I think "promising" is more aimed at the investors than a reflection of reality. Both Alkahest and Ambrosia's results are essentially ambiguous,

Safe, yes, but I think "promising" is more aimed at the investors than a reflection of reality. Both Alkahest and Ambrosia's results are essentially ambiguous, which reflects the equally ambiguous animal data for plasma transfusion. This isn't going to stop other people from trying analogous things. The Conboys are trying apheresis to strip out harmful factors from old blood ( https://www.leafscience.org/conboy-interview/ https://www.leafscience.org/conboy-interview/ ), which seems to me unlikely to move the needle either, and other groups are trying to identify and deliver signals from young blood. What all of these things have in common is that they are failing to address root causes. Why does signaling change in old blood and tissues? Because the cells that generate that signaling are either damaged or reacting to damage. Trying to force the signaling to be more youthful has very definite limits - it might compensate a little for one consequence of the damage, but that damage is still there, still producing all of the other problems that it causes. The "change the signaling" approach requires the research community to map every single one of potentially hundreds or thousands of individual changes, then understand which are relevant, and then run individual projects for each one. It just won't happen - look at the cancer research community for a guide as to how slowly that sort of scenario progresses. The plausible outer limits of signaling adjustment are probably indicated by the effects of first generation stem cell therapies, which largely work through the signals introduced by the transplanted cells. Assume that something somewhat better than that can be achieved: meaning temporarily improved regeneration, less increased cancer risk than was originally suspected, but not much of an impact on aging and age-related disease, when considered in the context of the bigger picture of what is possible. (What is possible if people would just stop tinkering with downstream consequences and start repairing the root cause damage. At least the flurry of interest in senolytics is a start in that direction, and should hopefully prove the point by being so very much better and more cost-effective than just about everything else on the market when it comes to treating age-related conditions).

JPLeRouzic 9y ago
Using senolytics is also trying the brute force approach. And what about targeting the level of cytokines? The immune system is sometimes running on free wheels (aging, autoimmune, etc) Let the body regulates itself.
- reasonattlm 9y ago
  Senolytics, to clear senescent cells, is a fundamentally different and more theoretically sound approach in comparison to trying to override signaling that is partially downstream of the presence of senescent cells. It also works far more reliably and for many more aspects of aging in mice. Senescent cells are one of the root cause of aging. Signaling changes in old blood are downstream of the root causes of aging - secondary and later consequences. Senescent cells are created by the operation of normal processes of healthy, youthful metabolism, and if their numbers can be periodically culled, then their contribution to aging will be removed. If your car is flagging, you repair the engine by replacing a damaged part, not by pressing the accelerator harder. Removing senescent cells is replacing a damaged part. Overriding signaling changes is pressing harder on the accelerator, while ignoring the damage.
  - nonbel 9y ago
    >"If your car is flagging, you repair the engine by replacing a damaged part, not by pressing the accelerator harder. Removing senescent cells is replacing a damaged part." Removing != replacing. What are you replacing the senescent cells with?
    - reasonattlm 9y ago
      They amount to a few percent of tissues in most cases. In mitotic tissues they will be replaced in the same way as any cell is replaced when it dies, by replication. In post-mitotic tissue cell therapy might be needed, but that hasn't so far been an issue in mice. It might be an issue for the human brain. Remains to be seen.
      - nonbel 9y ago
        >"In mitotic tissues they will be replaced in the same way as any cell is replaced when it dies, by replication." Replication from where though? The tissue stem cell that has already divided too many times?
danieltillett 9y ago
All of these approaches are going to run into the reason why ageing is happening in the first place - to prevent cancer. Ageing is one of the original anti-oncogenic systems and anything that messes with the rate of aging without doing something about cancer is doomed to failure. Interesting there are some human mutations that slow down the ageing rate [1]. These all cause an increased cancer rate, but if you manage to make it to old age you are physiologically much younger (20-30 years in the case of the Brazilian p53 mutation). 1. https://www.ncbi.nlm.nih.gov/pubmed/27663983 https://www.ncbi.nlm.nih.gov/pubmed/27663983
- touringcomplete 9y ago
  Exercise, sleep, socializing, sex, reducing stress and a carefully constructed diet clearly messes with the rate of aging. How would those be doomed? Also, perhaps the target and antitarget pathways of each could be isolated and modulated for maximum benefit?
- nonbel 9y ago
  >"if you manage to make it to old age you are physiologically much younger (20-30 years in the case of the Brazilian p53 mutation)." That sounds interesting, but I can't find it. Can you quote the part of that paper you are talking about?
  - danieltillett 9y ago
    Have a look at this NIH talk [1]. 1. https://youtu.be/URKJ7LLXc3E https://youtu.be/URKJ7LLXc3E
    - nonbel 9y ago
      Are you saying that info was not in your original source? I'm not willing to spend 15 minutes watching a video to possibly get this info. I have low hopes since the speaker probably cannot cite their source in that format. Can you tell me what minute of the video I should watch?
gone35 9y ago
OT: just wanted to say Fight Aging [1] is an amazing, inspiring model for how modern public interest initiatives should work IMO. Thank you. [1] https://www.fightaging.org https://www.fightaging.org

JPLeRouzic 9y ago

Using senolytics is also trying the brute force approach. And what about targeting the level of cytokines? The immune system is sometimes running on free wheels (aging, autoimmune, etc) Let the body regulates itself.

reasonattlm 9y ago
Senolytics, to clear senescent cells, is a fundamentally different and more theoretically sound approach in comparison to trying to override signaling that is partially downstream of the presence of senescent cells. It also works far more reliably and for many more aspects of aging in mice. Senescent cells are one of the root cause of aging. Signaling changes in old blood are downstream of the root causes of aging - secondary and later consequences. Senescent cells are created by the operation of normal processes of healthy, youthful metabolism, and if their numbers can be periodically culled, then their contribution to aging will be removed. If your car is flagging, you repair the engine by replacing a damaged part, not by pressing the accelerator harder. Removing senescent cells is replacing a damaged part. Overriding signaling changes is pressing harder on the accelerator, while ignoring the damage.
- nonbel 9y ago
  >"If your car is flagging, you repair the engine by replacing a damaged part, not by pressing the accelerator harder. Removing senescent cells is replacing a damaged part." Removing != replacing. What are you replacing the senescent cells with?
  - reasonattlm 9y ago
    They amount to a few percent of tissues in most cases. In mitotic tissues they will be replaced in the same way as any cell is replaced when it dies, by replication. In post-mitotic tissue cell therapy might be needed, but that hasn't so far been an issue in mice. It might be an issue for the human brain. Remains to be seen.
    - nonbel 9y ago
      >"In mitotic tissues they will be replaced in the same way as any cell is replaced when it dies, by replication." Replication from where though? The tissue stem cell that has already divided too many times?

danieltillett 9y ago

All of these approaches are going to run into the reason why ageing is happening in the first place - to prevent cancer. Ageing is one of the original anti-oncogenic systems and anything that messes with the rate of aging without doing something about cancer is doomed to failure. Interesting there are some human mutations that slow down the ageing rate [1]. These all cause an increased cancer rate, but if you manage to make it to old age you are physiologically much younger (20-30 years in the case of the Brazilian p53 mutation). 1. https://www.ncbi.nlm.nih.gov/pubmed/27663983 https://www.ncbi.nlm.nih.gov/pubmed/27663983

touringcomplete 9y ago
Exercise, sleep, socializing, sex, reducing stress and a carefully constructed diet clearly messes with the rate of aging. How would those be doomed? Also, perhaps the target and antitarget pathways of each could be isolated and modulated for maximum benefit?
nonbel 9y ago
>"if you manage to make it to old age you are physiologically much younger (20-30 years in the case of the Brazilian p53 mutation)." That sounds interesting, but I can't find it. Can you quote the part of that paper you are talking about?
- danieltillett 9y ago
  Have a look at this NIH talk [1]. 1. https://youtu.be/URKJ7LLXc3E https://youtu.be/URKJ7LLXc3E
  - nonbel 9y ago
    Are you saying that info was not in your original source? I'm not willing to spend 15 minutes watching a video to possibly get this info. I have low hopes since the speaker probably cannot cite their source in that format. Can you tell me what minute of the video I should watch?

gone35 9y ago

OT: just wanted to say Fight Aging [1] is an amazing, inspiring model for how modern public interest initiatives should work IMO. Thank you. [1] https://www.fightaging.org https://www.fightaging.org