Induction of the Transcription Factor FOXM1 Drives Healthspan Extension in Progeroid and Naturally Aged Mice

Elsa Logarhino

Dr. Elsa Logarinho, i3S Association, University of Porto, Portugal, will join Skin Ageing & Challenges 2022 to give a presentation entitled “Induction of the Transcription Factor FOXM1 Drives Healthspan Extension in Progeroid and Naturally Aged Mice”.

Aging is characterized by a gradual loss of function occurring at the molecular, cellular, tissue, and organismal levels, which represents a major risk factor for prevalent chronic conditions and declining overall health. Accumulating evidence has pointed that genomic instability affects most, if not all, aspects of the aging phenotype, thus targeting genomic instability appears a logical rationale for developing unified interventions to counteract age-related dysfunction and disease.

Dr. Logarinho’s team hypothesized that induction of FOXM1 transcription factor perfectly fits in this rationale since this gene influences a wide spectrum of biological functions (pleiotropy), including genomic stability. Indeed, they previously found that 60% of the aging-associated transcriptional changes in human dermal fibroblasts are FOXM1-dependent, with FOXM1 induction preventing genomic instability and the premature onset of cellular senescence.

Thus, the team asked if FOXM1 transgene (FOXM1tg) expression could also amend organismal aging, in both pathological and physiological contexts. We found that FOXM1tg cyclic induction offsets aging-associated repression of endogenous FoxM1, translating into mitigation of several cellular aging hallmarks, including genomic instability, epigenetic shifts, and senescence. The cyclic induction scheme ameliorated the severe skeletal defects, lipodystrophy and cardiac dysfunction of the short-lived Hutchison-Gilford progeria mice, attenuating senescence-associated histopathology and pro-inflammatory factors in the serum. Moreover, they found that FOXM1tg counteracts physiological aging phenotypes by modulating tissue-specific molecular signatures of pro-inflammatory and metabolic pathways, that positively correlate with some established lifespan-extension interventions.

Dr. Logarinho and her team conclude that FOXM1tg induction could be an effective therapy for progeria and age-related diseases.

Skin Ageing & Challenges 2022
November 17-18, 2022 – Lisbon, Portugal