Stem cell aging: mechanisms, regulators and therapeutic opportunities

Abstract

Aging tissues experience a progressive decline in homeostatic and regenerative capacities, which has been attributed to degenerative changes in tissue-specific stem cells, stem cell niches and systemic cues that regulate stem cell activity. Understanding the molecular pathways involved in this age-dependent deterioration of stem cell function will be critical for developing new therapies for diseases of aging that target the specific causes of age-related functional decline. Here we explore key molecular pathways that are commonly perturbed as tissues and stem cells age and degenerate. We further consider experimental evidence both supporting and refuting the notion that modulation of these pathways per se can reverse aging phenotypes. Finally, we ask whether stem cell aging establishes an epigenetic 'memory' that is indelibly written or one that can be reset.

Conflict of interest statement

COMPETING FINANCIAL INTERESTS

The authors declare no competing financial interests.

Figures

Figure 1

Common pathways contributing to stem cell loss and dysfunction in the aging process. Common aging phenotypes within the stem cell are shown in orange, in the niche in pink, and the strategies by which to target and hopefully reverse these mechanisms in blue.

Figure 2

Types of DNA damage in the aging genome that may affect stem cell function. Products of and effectors of DNA damage known to increase and accumulate during aging are shown, along with their effects on stem cell aging. CPD, cyclobutane pyrimidine dimer; DSB, double-strand break.

Figure 3

Signaling pathways involved in aging of stem cells. Major signaling pathways related to aging of stem cells are listed in groups according to stem cell functions that they regulate.