Aging alters tissue resident mesenchymal stem cell properties

Abstract

Tissue resident mesenchymal stem cells (MSCs) are known to participate in tissue regeneration that follows cell turnover, apoptosis, or necrosis. It has been long known that aging impedes an organism's repair/regeneration capabilities. In order to study the age associated changes, the molecular characteristics of adipose tissue derived MSCs (ASCs) from three age groups of healthy volunteers, i.e., young, middle aged, and aged were investigated. The number and multilineage differentiation potential of ASCs declined with age. Aging reduces the proliferative capacity along with increases in cellular senescence. A significant increase in quiescence of G2 and S phase was observed in ASCs from aged donors. The expression of genes related to senescence such as CHEK1 and cyclin-dependent kinase inhibitor p16(ink4a) was increased with age, however genes of apoptosis were downregulated. Further, an age-dependent abnormality in the expression of DNA break repair genes was observed. Global microRNA analysis revealed an abnormal expression of mir-27b, mir-106a, mir-199a, and let-7. In ubiquitously distributed adipose tissue (and ASCs), aging brings about important alterations, which might be critical for tissue regeneration and homeostasis. Our findings therefore provide a better understanding of the mechanism(s) involved in stem cell aging and regenerative potential, and this in turn may affect tissue repair that declines with aging.

Influence of Donor Age and Passage Number on Angiogenic Activity in Human Adipose-Derived Stem Cell-Conditioned Media

“…The results are in agreement with previous studies showing an age-associated decline in proliferative and clonogenic capacities in human bone marrow MSCs [37,38] and human ASCs [24,39,40]. The expression of the senescence-related genes p16…”

“…INK4a and CHK1 increases with age in human ASCs [24]. Bone marrow MSCs from patients aged over 40 years show increased levels of reactive oxygen species (ROS) and nitric oxide (NO) and impaired stress responses [37].…”

“…The proliferation and differentiation potential of MSCs/ASCs is known to be affected by in vitro aging (passage number in culture) [18][19][20][21] and by in vivo aging (donor age) [18,20,[22][23][24][25]. On the other hand, limited information is currently available regarding the angiogenic potential of aged ASCs [26][27][28].…”

Adipose-Derived Mesenchymal Stromal Cells From Aged Patients With Coronary Artery Disease Keep Mesenchymal Stromal Cell Properties but Exhibit Characteristics of Aging and Have Impaired Angiogenic Potential

“…Most of the data regarding ADSC regenerative potential were obtained from cells delivered from relatively healthy young donors; however, it was known that aging and disease itself may negatively affect MSC activities [21][22][23][24][25][26], including proliferation and differentiation potential [27][28][29][30] as well as angiogenic properties [29,31]. Because MSCs are considered to be components of the vessel wall and take part in its reparation after injury, their cellular modification due to aging can be an important pathogenic factor of agerelated diseases such as atherosclerosis, diabetes, and arterial hypertension [32].…”

Local delivery of tetramethylpyrazine eliminates the senescent phenotype of bone marrow mesenchymal stromal cells and creates an anti‐inflammatory and angiogenic environment in aging mice

“…However, the proliferation and function of MSCs are largely impaired during aging (Alt et al., 2012; Fehrer, Laschober, & Lepperdinger, 2006). Bonyadi et al.…”