A Review of the Recent Advances Made with SIRT6 and its Implications on Aging Related Processes, Major Human Diseases, and Possible Therapeutic Targets

Biomolecules. 2018 Jun 29;8(3):44. doi: 10.3390/biom8030044.

Abstract

Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide⁺ (NAD⁺) dependent enzyme and stress response protein that has sparked the curiosity of many researchers in different branches of the biomedical sciences. A unique member of the known Sirtuin family, SIRT6 has several different functions in multiple different molecular pathways related to DNA repair, glycolysis, gluconeogenesis, tumorigenesis, neurodegeneration, cardiac hypertrophic responses, and more. Only in recent times, however, did the potential usefulness of SIRT6 come to light as we learned more about its biochemical activity, regulation, biological roles, and structure Frye (2000). Even until very recently, SIRT6 was known more for chromatin signaling but, being a nascent topic of study, more information has been ascertained and its potential involvement in major human diseases including diabetes, cancer, neurodegenerative diseases, and heart disease. It is pivotal to explore the mechanistic workings of SIRT6 since future research may hold the key to engendering strategies involving SIRT6 that may have significant implications for human health and expand upon possible treatment options. In this review, we are primarily concerned with exploring the latest advances in understanding SIRT6 and how it can alter the course of several life-threatening diseases such as processes related to aging, cancer, neurodegenerative diseases, heart disease, and diabetes (SIRT6 has also shown to be involved in liver disease, inflammation, and bone-related issues) and any recent promising pharmacological investigations or potential therapeutics that are of interest.

Keywords: Alzheimer’s Disease; SIRT6; aging; cancer; cardiac hypertrophy; diabetes; gluconeogenesis; heart disease; neurodegeneration; neurodegenerative diseases; pharmacological SIRT6 inhibitor; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Chromatin / genetics*
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Gene Expression Regulation
  • Heart Diseases / drug therapy
  • Heart Diseases / genetics
  • Heart Diseases / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Sirtuins / chemistry*
  • Sirtuins / genetics
  • Sirtuins / metabolism*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / pharmacology
  • Small Molecule Libraries / therapeutic use
  • Structure-Activity Relationship

Substances

  • Chromatin
  • Small Molecule Libraries
  • SIRT6 protein, human
  • Sirtuins