AI Article Synopsis
- Aging is associated with functional decline and mitochondrial dysfunction, largely due to decreased NAD levels and increased activity of the enzyme CD38.
- Research indicates that inhibiting CD38 can improve mitochondrial function in various tissues, but its specific impact on NAD levels and metabolism in the aging brain is still unclear.
- This study reveals that while CD38 does not affect overall NAD levels or mitochondrial oxygen consumption in aging brains, it plays a crucial role in regulating hydrogen peroxide production related to mitochondrial function, suggesting a new link between CD38 and brain energy metabolism in aging.
Article Abstract
Aging is a time-related functional decline that affects many species. One of the hallmarks of aging is mitochondrial dysfunction, which leads to metabolic decline. The NAD decline during aging, in several tissues, correlates with increase in NADase activity of CD38. Knock out or pharmacological inhibition of CD38 activity can rescue mitochondrial function in several tissues, however, the role of CD38 in controlling NAD levels and metabolic function in the aging brain is unknown. In this work, we investigated CD38 NADase activity controlling NAD levels and mitochondrial function in mice brain with aging. We demonstrate that NADase activity of CD38 does not dictate NAD total levels in brain of aging mice and does not control mitochondrial oxygen consumption nor other oxygen parameters markers of mitochondrial dysfunction. However, for the first time we show that CD38 regulates hydrogen peroxide (HO) generation, one of the reactive oxygen species (ROS) in aging brain, through regulation of pyruvate dehydrogenase and alfa-ketoglutarate dehydrogenase, as mitochondria HO leakage sites. The effect may be related to mitochondrial calcium handling differences in CD38 absence. Our study highlights a novel role of CD38 in brain energy metabolism and aging.
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| http://dx.doi.org/10.1016/j.freeradbiomed.2023.09.035 | DOI Listing |
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