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Published on: September 28, 2017
NAD+ controls circadian rhythmicity during cardiac aging
Bryce J Carpenter1,2,3, Margaux Lecacheur1,2,3, Yannick N Mangold1,3
1Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
Aging disrupts the heart's daily rhythms and lowers NAD+. Supplementing with nicotinamide riboside (NR) restores NAD+ levels, resets the cardiac clock, and reverses age-related heart enlargement in mice.
Area of Science:
- Gerontology and Cardiovascular Science
- Circadian Biology and Metabolism
Background:
- Aging is characterized by circadian clock disruption and decreased NAD+ levels.
- The interplay between circadian rhythms and NAD+ metabolism in cardiac aging remains poorly understood.
Purpose of the Study:
- To investigate the relationship between cardiac circadian rhythms and NAD+ metabolism during aging.
- To determine the effects of NAD+ precursor supplementation on cardiac aging.
Main Methods:
- Analysis of diurnal gene expression in the aging mouse heart.
- Long-term supplementation with nicotinamide riboside (NR) in aged female mice.
- Assessment of NAD+ levels and PER2::luc oscillations in cardiomyocytes.
- Investigation of SIRT1 activity in response to NR treatment.
Main Results:
- Aging disrupts diurnal gene expression patterns in the heart.
- NR supplementation restored NAD+ levels, reprogrammed the cardiac transcriptome, and reversed cardiac enlargement in aged mice.
- Reduced NAD+ impaired cardiomyocyte circadian oscillations, which were rescued by NR.
- NR-induced transcriptomic changes were partially dependent on SIRT1 activity.
Conclusions:
- NAD+ plays a critical role in regulating the cardiac circadian clock during aging.
- NR supplementation offers a potential therapeutic strategy to counteract age-related cardiac dysfunction.
- This research highlights novel avenues for addressing cardiovascular disorders associated with aging.
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