Characterization of transcriptional landscape in bone marrow-derived mesenchymal stromal cells treated with aspirin by RNA-seq

Abstract

Introduction Aspirin is a common antipyretic, analgesic, and anti-inflammatory drug, which has been reported to extend life in animal models and application in the treatment of aging-related diseases. However, it remains unclear about the effects of aspirin on bone marrow-derived mesenchymal stromal cells (BM-MSCs). Here, we aimed to analyze the influence of aspirin on senescence and young BM-MSCs. Methods BM-MSCs were serially passaged to construct a replicative senescence model. SA-β-gal staining, PCR, western blot, and RNA-sequencing were performed on BM-MSCs with or without aspirin treatment, to examine aspirin’s impact on bone marrow-derived mesenchymal stem cells. Results SA-β-gal staining, PCR, and western blot revealed that aspirin could alleviate the cellular expression of senescence-related indicators of BM-MSCs, including a decrease of SA-β-gal-positive cells and staining intensity, and downregulation of p16, p21, and p53 expression after aspirin treatment. RNA-sequencing results shown in the biological processes related to aging, aspirin could influence cellular immune response and lipid metabolism. Conclusion The efficacy of aspirin for retarding senescence of BM-MSCs was demonstrated. Our study indicated that the mechanisms of this delay might involve influencing immune response and lipid metabolism.

Differentially Expressed Genes and Molecular Susceptibility to Human Age-Related Diseases

“…The total number of DEGs found in 22 original works [ 30 , 32 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ] was 37,834 in 17 tissues of five animal species. Figure 2 shows our procedure of comparison of 37,834 animal ARD-linked DEGs ( Table 4 ) with the 39 PAG-related DEGs of the tame and aggressive rats ( Table 2 ).…”

“…As can be seen from this table, only one of the 39 novel DEGs in the PAG of the tame and aggressive rats is linked with PC1, namely Fcgr2b encoding Fcγ receptor IIb, which suppresses the hyperactivation of immune cells [ 199 ] ( Table 7 ). Entries in this table suggest that the immunoregulatory DEGs homologous to rat Fcgr2b are significantly overexpressed in ARD-susceptible human and animal subjects compared to their ARD-resistant peers [ 35 , 39 , 43 , 51 , 55 , 56 , 58 ]. This leads us to propose that an excess of the immunoregulators homologous to rat Fcgr2b might be regarded as a candidate theranostic molecular marker for human ARDs.…”

“…Furthermore, some diets enriched for fat [ 29 ], calcium [ 30 ], or citrates [ 31 ] can provoke ARDs, as do long-term hunger, malnutrition, anorexia, and appetite loss [ 32 ]. By contrast, moderate physical exercise [ 33 ], short-term fasting [ 34 ], and low-dose aspirin [ 35 ] can prevent such diseases.…”

“…This could be why mainstream transcriptome-profiling studies of ARD susceptibility versus ARD resistance in human volunteers [ 33 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] and animals [ 30 , 32 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 ] are focused on the differentially expressed genes (DEGs) that are specific to gender, age, tissues, and pathogeneses. All previous research contributes to progress in predictive, preventive, personalized, participatory (4P) medicine [ 65 ] and helps us understand where, how, why, when, and what disorders can affect people depending on their genetic background, medical history, and lifestyle.…”

“…Furthermore, we have recently profiled transcriptomes in the hippocampus [ 74 ] of tame versus aggressive rat strains, in which deficient β-protocadherins and β-hemoglobin were found to be the statistically significantly most common theranostic molecular markers for ARD-related hypertension. That is why we sequenced, in the same way, one more transcriptome, that of the periaqueductal gray matter (PAG), in the tame versus aggressive rats, identified the corresponding behavior-related PAG-associated DEGs in them, and compared these DEGs with their homologous PubMed-based [ 75 ] ARD-linked DEGs in animals [ 30 , 32 , 35 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 68 , 74 ] and humans [ 33 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ] to find out whether there are invariant molecular markers for such diseases among them.…”