Calorie restriction modulates redox-sensitive AP-1 during the aging process

Area of Science:

• Gerontology
• Molecular Biology
• Biochemistry

Background:

• Oxidative stress is implicated as a primary driver of aging.
• Calorie restriction (CR) shows potential in extending lifespan by retarding aging, possibly via redox regulation.
• The impact of aging and CR on the redox-sensitive transcription factor activator protein-1 (AP-1) remains underexplored.

Purpose of the Study:

• To investigate the age-dependent changes in AP-1 status within the kidney.
• To determine if CR modulates the effects of aging on AP-1 activity.
• To elucidate the molecular mechanisms underlying AP-1 regulation by age and CR.

Main Methods:

• Utilized male Fischer 344 rats aged 6, 12, 18, and 24 months.
• Compared rats fed ad libitum (AL) with those on a CR diet.
• Assessed AP-1 binding activity, c-Jun and c-Fos protein levels, and c-Jun phosphorylation in kidney tissue.
• Examined the expression of AP-1 target genes, matrix metalloproteinase-13 (MMP-13) and heme oxygenase-1 (HO-1).

Main Results:

• AP-1 binding activity significantly increased with age in rat kidneys.
• CR maintained AP-1 activity at levels observed in young (6-month-old) rats.
• Aging led to elevated c-Jun and c-Fos protein levels and increased c-Jun phosphorylation.
• CR blunted AP-1 activation in aged rats by reducing c-Jun/c-Fos levels and inhibiting c-Jun phosphorylation.
• AP-1 target genes (MMP-13, HO-1) exhibited expression patterns mirroring AP-1 binding activity.

Conclusions:

• Kidney AP-1 activity escalates with age in rats.
• Calorie restriction effectively attenuates age-associated AP-1 activation in the kidney.
• These findings highlight AP-1 as a key molecular target modulated by aging and CR, potentially influencing longevity and age-related decline.