Pro-Longevity Role of SIRT6 to Promote Life Span and Delay Ageing – An Integrated Review Towards Healthy Ageing

Ageing is an outcome of insufficient maintenance of the internal environment. Over time, each component of the internal environment changes from the molecular level to the organismal level to maintain homeostasis. These changes occur through several biological pathways, such as adenosine monophosphate-activated protein kinase (AMPK), nuclear factor erythroid 2-related factor (Nrf), mitogen-activated protein kinase (MAPK), mechanistic target of rapamycin (mTOR), and several others. Researchers are vigorously focused on these pathways and their gene regulators. In the past discovery, sirtuin came into play for improving cellular activity and promoting healthy ageing through these pathways of ageing. Out of seven isoforms of sirtuin, sirtuin 6 (SIRT6) is constantly gaining importance for its involvement in reducing oxidative stress, promoting nicotinamide adenine dinucleotide (NAD + ) activity, cardiovascular health, etc. It is shown to play a significant role in regulating the diverse functions of multiple organ systems at the cellular and molecular level through its unique enzymatic activity. Similar to SIRT1, SIRT6 is also seen in anti-ageing pathways and disease discovery. However, its function and target pathways are not yet clear. This review will attempt to evaluate the existing literature and formulate a framework for its role in longevity, which can be considered as a novel target for promoting healthy ageing.