Ageing as developmental decay: insights from p16(INK4a.).
Nadine Martin1, David Beach2, Jesús Gil1
1Cell Proliferation Group, Medical Research Council (MRC) Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London W12 0NN, UK.
Trends in Molecular Medicine
|October 4, 2014
Summary
Ageing may be driven by the decay of developmental pathways, as shown by the cell cycle regulator p16(INK4a). This biomarker
Area of Science:
- Gerontology
- Developmental Biology
- Molecular Biology
Background:
- The p16(INK4a) protein is a key cell cycle regulator.
- p16(INK4a) levels are low in early development and increase with age.
- It influences cellular senescence and stem cell behavior, processes linked to aging.
Purpose of the Study:
- To propose the "developmental decay hypothesis" of aging.
- To link the regulation of p16(INK4a) to developmental pathways.
- To suggest that aging damage may be secondary to pathway decay.
Main Methods:
- Review of existing literature on p16(INK4a) regulation.
- Analysis of the role of p16(INK4a) in aging and development.
- Synthesis of data to support the developmental decay hypothesis.
Main Results:
- p16(INK4a) regulation pathways overlap with those in early development.
- Ageing involves progressive induction of p16(INK4a).
- The functional decay of developmental pathways could drive aging.
Conclusions:
- Aging may result from the gradual decline of fundamental developmental processes.
- The observed damage in aging might be a consequence of this decay.
- p16(INK4a) serves as a critical biomarker connecting development and aging.
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