The forkhead transcription factor, Foxo1, coordinates an adaptive, pro-survival response to calorie restriction in T cells (47.3)

Abstract

Abstract In addition to longevity enhancement, calorie restriction has been reported to slow the appearance of aging-related T cell abnormalities. However, the molecular mechanism underlying this phenomenon in T cells is ill-defined. We report that short-term calorie restriction in wild type mice inhibited the spontaneous apoptosis of naïve CD8+ T cells by approximately three fold, as compared to cells isolated from mice fed ad libitum. An ortholog of the forkhead transcription factor, Foxo1, is required for the longevity benefits of calorie restriction in C. elegans. Therefore, mice with a conditional, T cell-specific deficiency of Foxo1 (Foxo1 cKO) were also subjected to calorie restriction. Indeed, the pathway through which calorie restriction results in reduced naïve CD8+ T cell apoptosis appears to involve Foxo1, as calorie restriction in the absence of Foxo1 did not result in reduced naïve CD8+ T cell apoptosis. Instead, naïve CD8+ T cell apoptosis was similarly high for cells isolated from ad libitum wild type, ad libitum Foxo1 cKO, and calorie restricted Foxo1 cKO mice. Thus, Foxo1 coordinates an adaptive, pro-survival transcriptional response to calorie restriction. To our knowledge, Foxo1 is the first transcription factor identified to contribute to this process in mice.