The role of adult mesenchymal stem cells (MSC) in tissue maintenance and regeneration has received significant attention of late. Questions arise to what extent these cells are either subject to, or causes of aging; whether age-related changes in these cells are due to intrinsic factors or induced by the somatic environment. This review collates and examines recent data in support of these different theories. By means of introduction, a brief overview is given of current MSC definitions and their basic role in tissue regeneration followed by a comparative analysis of gerontological studies involving MSC. Evidence for extrinsic aging and various aging markers relating to morphology, proliferation, signalling, senescence markers, telomeres and telomerase, and other indicators is discussed. We observe that while the literature might often appear to conflict, many apparent discrepancies are attributable to inconsistent methods of extracting and isolating MSC which in fact contains various subsets of adult stem cells, varying not only in their differentiation potential but also in their vulnerability to senescence—ranging from quasi-somatic lifespan to perennial vigour. Thus, mesenchymal stem cells emerge as both subject to and key mediators of organismal aging.