Δ133p53α, a senescence-inhibitory p53 isoform, attenuates accelerated aging in progeria mice

Abstract Research on progeria not only contributes to the development of treatments for the disease but also enhances our understanding of physiological aging. In a mouse model of Hutchinson-Gilford progeria syndrome (HGPS), transgenic expression of Δ133p53α, a senescence-inhibitory human p53 isoform, reduced the expression of p21 Waf1/Cip1 (a mediator of cellular senescence), IL-6 (a proinflammatory cytokine), and γ-H2AX (a marker of DNA double-strand breaks) across multiple tissues. In the tissues primarily affected in HGPS, Δ133p53α prevented characteristic pathological changes, represented by preservation of aortic vascular smooth muscle cells, skin dermis and dermal white adipose tissue, and a hair follicle stemness marker. Δ133p53α also mitigated spinal kyphosis and led to a modest increase in median lifespan. We also present preliminary data supporting beneficial effects of Δ133p53α in naturally aged mice and its possible relevance to human aging. This study warrants further investigation of Δ133p53α-based approaches for HGPS, and potentially for physiological aging.