Impaired SIRT1 nucleocytoplasmic shuttling in the senescent heart during ischemic stress

Increases in heart-related conditions have shifted the focus of the medical community towards protecting this all-important organ. Literally the engine of life, the heart undergoes tremendous stress at all times, making it a wonder it is able to do all that it can for as long as it does. However, the heart, not surprisingly, is not immune to aging. Over time, functionality decreases due to a number of factors, and this heightened vulnerability makes diseases and conditions far more likely. To be able to counteract this process with effective pharmacological treatments, researchers need to better understand exactly what goes on when the heart ages, and this was the focus of the study conducted by Tong et al. Specifically, they sought to determine the role of sirtuin 1 (SIRT1) in the tolerance of an aged heart to ischemic insults, largely because SIRT 1 has long been assumed to be an anti-aging protein due to the finding that Sir2 prolongs the life span of S. cerevisiae, C. elegans, and D. melanogaster. With this, they hoped to better understand the process of ischemic/reperfusion (I/R) stress, a leading cause of degrading heart function in older hearts.

To conduct this study, Tong's team used C57BL/6 male mice to study the interactions SIRT 1 with other important mitochondrial enzymes to see if they could better understand the process of I/R stress and what could be done about it. The results they obtained are rather interesting. First, they found that I/R stress leads to desumoylation and translocation of SIRT1 into the cytoplasm in aged hearts but not in young ones, and SIRT1 activity was actually 3.2 times higher than in aged hearts. One of the ways that Tong's team was able to conduct this study was by measuring NAD+, a substrate of SIRT1, because NAD+ plays a critical role in the function of SIRT1. The did this by using the Amplite Fluorimetric Total NAD and NADH Assay Kit. This is significant because the assay kit is able to produce far more accurate results than similar kits. Instead of measuring NAD by monitoring NADH or NADPH absorption, this kit uses a set of enzymes that specifically recognize NAD in an enzyme cycling reaction. This makes it far more sensitive and therefore produces results that are more accurate and reliable.

In the end, Tong et al. found that SIRT1 is predominantly expressed in cardiomyocyte nuclei as a sumoylated form that is integral to the heart's tolerance for ischemic stress. Specifically, the aged heart possesses lower SIRT1 protein levels and is less capable of activating SIRT1 in response to I/R. This is significant because this depressed reaction can be reversed with proper pharmacological treatment, suggesting a new way forward for treating certain conditions arising from the aging of the heart. The results of this study would not have been possible if it had not been for the accurate NAD measurements provided by the Amplite Fluorimetric Total NAD and NADH Assay Kit. The sensitivity of this assay allows for accurate results that can be used to make reliable conclusions that stand to dramatically improve the chances of combating certain life-threatening conditions.

References

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1. Tong, Chao, et al. "Impaired SIRT1 nucleocytoplasmic shuttling in the senescent heart during ischemic stress." The FASEB Journal 27.11 (2013): 4332-4342.