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Senolytics, to clear senescent cells, is a fundamentally different and more theoretically sound approach in comparison to trying to override signaling that is p

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?
    - reasonattlm 9y ago
      From other somatic cells, and ultimately from the tissue stem cell population. That population is impacted by aging, as you point out. However, the effects of replacing 1% of tissues over some period of time are going to be negligible in comparison to the effects of having 1% senescent cells, given that those senescent cells and the inflammatory, harmful signaling they generate are one of the reasons why the stem cell population is less active, and regeneration less effective.
      - nonbel 9y ago
        I guess no one knows for sure, but assuming errors accumulate after each cell division it'd make a lot of sense if, after some number of them, cell turnover slows and stops in order to avoid any further replication. In that case your plan would be treating the symptom, not the cause (accumulated genetic errors and whatever other junk in the stem cells). I would also expect it to lead to cancer.

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?
  - reasonattlm 9y ago
    From other somatic cells, and ultimately from the tissue stem cell population. That population is impacted by aging, as you point out. However, the effects of replacing 1% of tissues over some period of time are going to be negligible in comparison to the effects of having 1% senescent cells, given that those senescent cells and the inflammatory, harmful signaling they generate are one of the reasons why the stem cell population is less active, and regeneration less effective.
    - nonbel 9y ago
      I guess no one knows for sure, but assuming errors accumulate after each cell division it'd make a lot of sense if, after some number of them, cell turnover slows and stops in order to avoid any further replication. In that case your plan would be treating the symptom, not the cause (accumulated genetic errors and whatever other junk in the stem cells). I would also expect it to lead to cancer.