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Ink4a/Arf expression is a biomarker of aging
Janakiraman Krishnamurthy1, Chad Torrice, Matthew R Ramsey
1Department of Medicine, The Lineberger Comprehensive Cancer Center, The University of North Carolina School of Medicine, Chapel Hill, North Carolina, 27599-7295, USA.
The Journal of Clinical Investigation
|November 3, 2004
Summary
Cellular senescence, mediated by Ink4a/Arf, increases with age in rodents. Caloric restriction reduces this Ink4a/Arf expression, suggesting it
Area of Science:
- Molecular Biology
- Cell Biology
- Gerontology
Background:
- The Ink4a/Arf locus encodes tumor suppressors p16INK4a and Arf, key mediators of cellular senescence.
- Cellular senescence is implicated in the aging process.
Purpose of the Study:
- To investigate the relationship between senescence and aging in vivo.
- To examine Ink4a/Arf expression in rodent models across the lifespan.
Main Methods:
- Analysis of Ink4a/Arf gene expression in various rodent tissues.
- Assessment of gene expression changes in response to caloric restriction.
- Correlation of Ink4a/Arf expression with senescence markers and organ pathology.
Main Results:
- p16INK4a and Arf expression significantly increases in most rodent tissues with age.
- This age-associated increase is localized to specific cellular compartments and cell types.
- Caloric restriction attenuates Ink4a/Arf expression in the kidney, ovary, and heart, correlating with reduced senescence and pathology.
- Ets-1 and other coregulatory molecules contribute to age-related Ink4a/Arf expression.
Conclusions:
- Ink4a/Arf expression serves as a reliable biomarker for mammalian aging.
- Ink4a/Arf may play a direct role in the aging process.
- Caloric restriction can modulate senescence pathways associated with aging.