Combining Cell Replacement and Cell Ablation to Slow Aging

The authors of this paper propose that suitably tailored periodic destruction of cells combined with cell therapies to replace lost cells could have an impact on many of the forms of cell and tissue damage that cause aging. This is not something that can be achieved today with suitable control over the results at the detail level, but that level of control is a plausible target to aim for in the decades ahead. While looking this over, it might be worth recalling a study published last year in which researchers caused low-quality cells to be continuously destroyed in flies. There is an existing mechanism by which cells compare quality, connected to the triggering of programmed cell death, and the operation of these processes can be adjusted, as was the case in that study. The result was flies that lived 50% longer, an interesting result in this context.

In both biomedicine in general and biomedical gerontology in particular, cell replacement therapy is traditionally proposed as an intervention for cell loss. This paper presents a proposed intervention - Whole-body Induced Cell Turnover (WICT) - for use in biomedical gerontology that combines cell replacement therapy with a second therapeutic component so as to broaden the therapeutic utility of cell therapies and increase the categories of age-related damage that are amenable to cell-based interventions. In particular, WICT may allow cell therapies to serve as an intervention for accumulated cellular and intracellular damage, such as telomere depletion, gDNA and mtDNA damage and mutations, replicative senescence, functionally-deleterious age-related changes in gene expression, accumulated cellular and intracellular aggregates and functionally-deleterious post-translationally modified gene products.

WICT consists of the gradual ablation and subsequent replacement of a patient's entire set of constituent cells gradually over the course of their adult lifespan via the quantitative and qualitative coordination of targeted cell ablation with exogenous cell administration. The aim is to remove age-associated cellular and intracellular damage present in the patient's endogenous cells. Here we outline the underlying techniques and technologies by which WICT can be mediated, describe the mechanisms by which it can serve to negate or prevent age-related cellular and intracellular damage, explicate the unique therapeutic components and utilities that distinguish it as a distinct type of cell-based intervention for use in biomedical gerontology and address potential complications associated with the therapy.

Link: http://dx.doi.org/10.1089/rej.2015.1763

Comments

Yes I have a copy of this paper it is an interesting idea and something we talked about in the context of AGE.

We are also looking at Senolytics followed by Stem cell replacement as one of our combination tests in later phases of the MMTP. Considering our line of work and that we have a world class stem cell researcher on our team this is certainly plausible for us to try.

Posted by: Steve H at January 26th, 2016 4:58 AM

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