Senescence-inhibitory Δ133p53α counteracts accelerated ageing and mortality

Area of Science:

• Gerontology
• Molecular Biology
• Genetics

Background:

• Progeria research offers insights into physiological aging.
• Progeria mouse models exhibit aging phenotypes like cardiovascular defects and shortened lifespan.
• The p53 isoform Δ133p53α inhibits senescence and inflammation in Hutchinson-Gilford progeria syndrome (HGPS) cells.

Purpose of the Study:

• To investigate the in vivo effects of transgenic Δ133p53α expression in a mouse model of HGPS.
• To determine if Δ133p53α can ameliorate aging phenotypes and extend lifespan in vivo.
• To explore the potential of Δ133p53α as a therapeutic strategy for HGPS and aging.

Main Methods:

• Transgenic expression of Δ133p53α in a heterozygous HGPS mouse model.
• Assessment of pathological changes in multiple organs, including aorta and skin.
• Evaluation of lifespan extension and various aging-counteracting mechanisms.

Main Results:

• Transgenic Δ133p53α expression extended median lifespan by 11% in HGPS mice.
• Δ133p53α abrogated progeria-associated pathological changes in aorta and skin.
• Δ133p53α demonstrated potential to promote bone homeostasis, metabolic fitness, and tissue stemness.

Conclusions:

• Δ133p53α reproduces in vitro anti-aging effects in vivo, extending lifespan in an HGPS mouse model.
• Δ133p53α preserves tissue integrity and may counteract broad aging mechanisms.
• Δ133p53α-based therapies show promise for treating HGPS and potentially delaying aging in general.