Age-related thymic involution: mechanisms of T-cell immunity remodeling

The review systematizes current concepts of the molecular, cellular, and neuroendocrine mechanisms underlying age-related thymic involution and its role in the development of immunosenescence and oncopathology. Key transcription factors (Foxn1, E2F3, Myc), signaling pathways (Notch/DLL4, PPARγ), and epigenetic regulators (miR–181a) coordinating the degradation of thymic epithelial cells and the replacement of parenchyma with adipose tissue are analyzed. Particular attention is paid to the role of sex steroids in inducing organ atrophy, the physiological characteristics of gestational involution (RANK/progesterone axis), and the protective effects of caloric restriction and the somatotropic axis (GH/IGF–1). From a clinical perspective, the impact of medullary compartment degradation on the distortion of negative selection and the accumulation of suppressive pools of regulatory T–cells (tTreg) that block antitumor surveillance in old age is characterized. The prospects of using T–cell receptor excision circles (TRECs) as a precision biomarker of true functional thymic senescence are substantiated.