Increasing evidence suggests that the loss of functional stem cells may be important in the aging process. Our experiments were originally aimed at testing the idea that, in the specific case of age-related osteoporosis, declining function of osteogenic precursor cells might be at least partially responsible. To test this, aging female mice were transplanted with mesenchymal stem cells from aged or young male donors. We find that transplantation of young mesenchymal stem cells significantly slows the loss of bone density and, surprisingly, prolongs the life span of old mice. These observations lend further support to the idea that age-related diminution of stem cell number or function may play a critical role in age-related loss of bone density in aging animals and may be one determinant of overall longevity. O steoporosis is a disease characterized by low bone mass and deteriorating bone structure leading to increased bone fragility and risk of fractures 1, 2 . This disease, primarily affecting older population, has placed a tremendous burden on the health care system 3,4 . Although advanced age is the best predictor of osteoporosis 1, 3 , the link between aging and osteoporosis is not fully understood. Our investigations, involving the simple strategy of introducing young bone marrow mesenchymal stem cells (BMSCs) into old recipients, were intended to test the possibility that age-related loss of functional stem cells might be at least partially responsible for this disorder. Extensive evidence suggests that osteoporosis is caused by complex interactions between endogenous (genetic and hormonal) and exogenous (nutritional and physical activity) factors regulating bone tissue remodeling 1, 5 . It is therefore thought that osteoporosis may be prevented by increased daily intake of calcium and vitamin D, appropriate and persistent exercise, hormone replacement and many other alternative therapies 2, 6 . However, none of these has been shown to be completely effective in preventing age-related osteoporosis. It has recently been proposed that a decrease of osteogenic progenitor cells within the bone marrow with advancing age might be related to osteoporosis 7, 8 . In this regard, a relative increase in the proportion of osteoclasts in aged bone may tilt the delicate balance between the bone-forming activity of osteoblasts and bone resorbing activity of osteoclasts 7, 8 . A related proposal suggests that aging bone marrow cells may shift from pro-osteoblastogenesis to pro-adipogenesis phenotypes, reflected by an accumulation of bone marrow fat with aging 9 . In partial support of this possibility, stem cells isolated from older donors have been shown to have defective functions, including impaired capacity of proliferation and differentiation in vitro, compared with those isolated from young individuals [10] [11] [12] . Despite of the latter observations, it remains uncertain whether aging of stem cells is responsible for the pathogenesis of age-related osteoporosis. To test the possible impact of aging on stem cell function, we have carried out a series of studies to compare the function of BMSCs isolated from young (1-2 months old) or old (20-24 months old) mice. To test whether defective stem cells function might be responsible for the progression of osteoporosis, old female mice were irradiated then transplanted with BMSCs from young or old males. The fate and function of transplanted BMSCs and their effect on bone mineral density of elderly recipient mice were then evaluated. Bone marrow stem cell isolation and characterization. Femoral BMSCs were isolated from 1-2 months old and 20-24 months old male EGFP transgenic C57BL/6 mice and Balb/c mice. BMSCs from young and old EGFP donors showed similar fibroblast-like spindle shape and green fluorescence ( Figure 1A ) following in vitro culture with similar doubling times of ,80 hours. Flow cytometry analyses showed that second passage cells from Balb/c
Originally studying the effect of BMT on osteoporosis, REF found that transplanting mesenchymal stem cells (MSC) from young to old mice not only significantly slowed the loss of bone density, but also prolonged the life span of old mice.
Transplantation of mesenchymal stem cells from young donors delays aging in mice
Scientific Reports
Scientific Reports
Biology Medicine