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Temporal linkage between the phenotypic and genomic responses to caloric restriction
Joseph M Dhahbi1, Hyon-Jeen Kim, Patricia L Mote
1BioMarker Pharmaceuticals, Incorporated, 900 East Hamilton Avenue, Campbell, CA 95008, USA.
Summary
Caloric restriction (CR) initiated in older mice significantly extends lifespan and reduces mortality. CR rapidly alters gene expression, suggesting potential therapeutic mimics for aging.
Area of Science:
- Gerontology
- Molecular Biology
- Genetics
Background:
- Caloric restriction (CR) is known to slow aging and age-related diseases.
- Its effectiveness in older individuals and impact on gene expression were previously unclear.
Purpose of the Study:
- To investigate the effects of initiating CR in aged mice on lifespan and gene expression.
- To determine if CR-induced gene expression changes correlate with health and longevity benefits.
Main Methods:
- CR was initiated in 19-month-old mice.
- Lifespan, mortality rates, and causes of death (including tumors) were analyzed.
- Genome-wide microarray analysis of liver gene expression was performed at various time points.
Main Results:
- CR increased mean lifespan by 4.7 months and maximum lifespan by 6.0 months.
- Age-associated mortality decreased 3.1-fold, and tumor-related deaths decreased significantly.
- CR rapidly shifted gene expression profiles toward those seen in long-term CR, correlating with health benefits.
Conclusions:
- CR initiated late in life can significantly extend lifespan and improve healthspan in mice.
- CR-induced gene expression changes are rapidly induced and reversible, suggesting a causal link to aging.
- Therapeutics mimicking CR's gene expression biomarkers may offer similar physiological benefits.