Hormonal
Overexpression of the short p53 isoform (p44) in mice accelerates aging and reduces lifespan by hyperactivating the IGF signaling axis, which triggers a kinase cascade that clamps cell proliferation via p21Cip1 induction.
This research highlights the complexity of the p53 pathway in aging. While reducing IGF signaling is often associated with longevity, this study shows that hyperactivating it via specific p53 isoforms can accelerate aging. This suggests that maintaining a balance between p53 isoforms is crucial for longevity, rather than simply maximizing or minimizing p53 activity.
Hyperactivation of the insulin-like growth factor (IGF) signaling axis by p44 sets in motion a kinase cascade that clamps potentially unimpeded growth through p21Cip1. This suggests that pathways of gene activity known to regulate longevity in lower organisms are linked in mammals via p53 to mechanisms for controlling cell proliferation.
Why this rating
High-quality genetic manipulation (transgenic mice) with clear phenotypic outcomes, though specific to a mouse model and not a human intervention.
Source
Modulation of mammalian life span by the short isoform of p53
Bernhard Maier et al. · Genes & Development · 2004
DOI 10.1101/gad.1162404
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