Restoring aged stem cell functionality: Current progress and future directions

Abstract

Stem cell dysfunction is a hallmark of aging, associated with the decline of physical and cognitive abilities of humans and other mammals [Cell 2013;153:1194]. Therefore, it has become an active area of research within the aging and stem cell fields, and various techniques have been employed to mitigate the decline of stem cell function both in vitro and in vivo. While some techniques developed in model organisms are not directly translatable to humans, others show promise in becoming clinically relevant to delay or even mitigate negative phenotypes associated with aging. This review focuses on diet, treatment, and small molecule interventions that provide evidence of functional improvement in at least one type of aged adult stem cell.

Keywords: adult stem cells; aged stem cells; aging; hematopoietic stem cells; interventions; intestinal stem cells; mesenchymal stem cells; muscle stem cells; neural stem cells; rejuvenation; skin stem cells; stem cells.

FIGURE 1

Aging phenotypes in adult stem cell compartments. ↑ indicates increase; ↓ indicates decrease; = indicates no change. ROS, reactive oxygens species

FIGURE 2

Targeted pathways by each treatment type based on cell-extrinsic and cell-intrinsic effects. Each unique target or pathway seen in multiple treatments has been highlighted in a unique color. HBE, Heterochronic Blood Exchange; YPI, Young Plasma Injections

FIGURE 3

We propose that progress in stem cell rejuvenation will be made by utilizing a combination of various strategies such as combining drugs, longitudinal studies, secretome isolation and amplification, nanoparticle delivery, single cell characterization, large scale drug screening, and artificial intelligence and machine learning guided targeting, discovery, and optimization of drugs