Longevity & AgingMRAP Protein Drives Thymus-to-Fat Conversion Behind Age-Related Immune Decline
As we age, the thymus — the organ responsible for producing T cells — progressively fills with fat, crippling immune function. This study identifies MRAP (melanocortin-2 receptor accessory protein) as a critical driver of this transformation. Thymic mesenchymal stromal cells (tMSCs) were found to preferentially differentiate into fat cells rather than bone, unlike MSCs from other tissues. MRAP expression surges in tMSCs during adipogenesis, and knocking it out dramatically reduces fat cell formation. The thymic peptide thymosin-α1 was found to trigger MRAP expression via the FoxO1 signaling pathway. Single-cell RNA sequencing of human thymus tissue confirmed that tMSCs and adipocytes accumulate with age, pointing to MRAP as a promising target to slow thymic fat deposition and preserve immune function during aging.
