|dc.description.abstract||The past century has seen remarkable advancements in the areas of science, health,
and longevity. However, as science progresses and lifespan continues to increase, age-related
metabolic diseases, such as hypertension and diabetes type 2, also continue to increase in
prevalence. It is imperative upon modern society to investigate and understand metabolic
pathways so that the diseases may be treated and human lifespan may continue to increase.
For years, calorie restriction has been known to slow aging and increase lifespan.
Previous experiments have shown that the enzyme SIRT6 increases in response to calorie
restriction, indicating that the enzyme may regulate the metabolic response to calorie
restriction (Gertler 2013). This study focuses on SIRT6 in order to understand its role in the
metabolic pathways during caloric restriction and starvation and thus, its role in increasing
During caloric restriction and starvation, glycolysis is inhibited and beta oxidation is
turned on. This study seeks to investigate the role of SIRT6 in beta oxidation. PPARA, a
protein that regulates beta oxidation gene expression, may be utilized to help establish the
connection between SIRT6 and beta oxidation.
Mice were treated with WY 14643, a PPARA agonist, to investigate SIRT6’s role in
beta oxidation and its relationship with PPARA. The WY treatment activates beta oxidation
and mimics starvation. The metabolites of treated wildtype mice were compared to those of
treated transgenic mice that were overexpressing SIRT6. Acylcarnitine intermediates and
organic acid were the two types of metabolites that were analyzed, as they both indicate beta
oxidation. Results showed that levels of pyruvate, an organic acid, were higher in the
transgenic mice than in the wildtype during the treatment, indicating that SIRT6 regulates
beta oxidation through PPARA. In addition, acylcarnitine levels of transgenic mice were
lower than those of wildtype mice, while levels of two-carbon molecules were higher in
transgenic mice than in wildtype mice. This data again demonstrates a SIRT6 regulatory role
in beta oxidation through PPARA.
The research establishes that SIRT6 plays a role in beta oxidation, specifically
through regulating PPARA. SIRT6 thus holds much promise for future metabolic disease