Whole-Body Induced Cell Turnover: A Proposed Intervention for Age-Related Damage and Associated Pathology.

Abstract

In both biomedicine in general and biomedical gerontology in particular, cell replacement therapy is traditionally proposed as an intervention for cell loss. This article 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 (targeted cell ablation) 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, genomic DNA and mitochondrial DNA damage and mutations, replicative senescence, functionally deleterious age-related changes in gene expression, accumulated cellular and intracellular aggregates, and functionally deleterious posttranslationally 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 life span through 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. In this study, 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.