Age-related changes in mesenchymal stem cells derived from rhesus macaque bone marrow

Area of Science:

• Stem cell biology
• Gerontology
• Regenerative medicine

Background:

• Mesenchymal stem cells (MSCs) possess regenerative potential that declines with age.
• This age-related decline is linked to altered cellular functions.
• Understanding these changes is crucial for optimizing stem cell therapies in aging populations.

Purpose of the Study:

• To investigate the impact of aging on rhesus bone marrow mesenchymal stem cells (rBMSCs).
• To analyze age-related changes in MSC proliferation, differentiation, circadian rhythms, stress response, miRNA expression, and histone modifications.

Main Methods:

• Comparison of rBMSCs from young (<5 years), middle (8-10 years), and old (>12 years) rhesus monkeys.
• Analysis of proliferation and differentiation capacities.
• Measurement of heat shock proteins (HSP70, HSF1), circadian protein (Rev-erb α), and miRNA expression profiles.
• Assessment of global histone modifications (H2A, H2B, H3, H4).

Main Results:

• rBMSCs showed reduced proliferation and differentiation with increasing age.
• Heat shock protein 70 (HSP70) and heat shock factor 1 (HSF1) levels decreased in older rBMSCs.
• Core circadian protein Rev-erb α levels increased in aged rBMSCs.
• Specific miRNAs (mir-766, mir-558) were upregulated, while others (mir-let-7f, mir-125b, mir-222, mir-199-3p, mir-23a, mir-221) were downregulated in older rBMSCs.
• No significant age-related changes were observed in global histone modifications.

Conclusions:

• Aging significantly impairs rBMSC function, affecting key cellular processes.
• Altered circadian rhythms and miRNA expression are novel indicators of MSC aging.
• These findings provide insights into the aging process and have implications for autologous stem cell therapy in elderly patients.