Interferon Regulatory Factor 7 (IRF7) inhibition reverts age induced transcriptional and metabolic derangement

Aging relies on incremental alterations of cell and tissue which contribute to deteriorate organ functions and progressively drives to death. We show herein that midlife brings about a massive transcriptional/metabolic reprogramming, reminiscent of a cell-autonomous activation of an ectopic anti-viral response, which impairs the biological functions on the basis of cell homeostasis and longevity, namely mitochondrial and amino acid biogenesis. Integrated transcriptional analyses indicate IRF7 to be the major driver of these changes reveling an unprecedented, cell-autonomous role of Interferon Regulatory Factor 7 (IRF7) in leading transcriptional, mitochondrial and amino acid alterations with age. We found that the inhibition of IRF7 is sufficient to revert the transcriptional profiling of “old cell”, determining diminished interferon signaling, reverted transcriptional derangement, restored mitochondrial function and partially reestablish the amino acid pool. Our results reveal IRF7 as a major regulator of aging-related transcriptional and metabolic alterations and point it out as an ideal candidate for the development of effective therapies against aging and aging-related diseases.