Hello Darul Raiyaan

Thymic involution is a physiological process that occurs naturally and progressively with aging. Atrophy occurs by a gradual and progressive decline in the number of thymocytes, and known mechanisms of physiological atrophy are mediated by either thymic epithelial cell (TEC) or thymocytes. Age-related TEC influencing factors such as sex steroids, cytokines, transcription factors, and microRNAs are involved. But the single most predominant mechanistic factor is the TEC autonomous transcription factor FOXN1, which is uniquely expressed in epithelial cells of the thymus. Gradual loss of FOXN1, which primarily regulates TEC differentiation and homeostasis, has been shown to be associated with age-related thymic involution.

It has been shown that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional TECs. In Rb family mutant TECs, increased activity of E2F transcription factors drives increased expression of FOXN1, a central regulator of the thymic epithelium. Increased FOXN1 expression is required for thymic expansion observed in Rb family mutant mice. Thus, the Rb family promotes thymic involution and controls T cell production via a bone marrow-independent mechanism.

The major consequence of thymic involution is the diminished production of naïve T lymphocytes. As a result, the peripheral immune repertoire is not replenished, and this is thought to contribute to impaired immunity in the elderly.

Attached below are a few references that you may want to refer.

Article Contributions of Age-Related Thymic Involution to Immunosene...

Article Transcriptional profile of human thymus reveals IGFBP5 is co...

Article Inactivation of the RB family prevents thymus involution and...

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