The flip side of sirtuins: the emerging roles of protein acetyltransferases in aging

Abstract

Protein N-ε-lysine acetylation is is an important post-translational modification that plays critical roles in the regulation of many cellular processes. A role for this modification in the process of aging goes back two decades to the discovery that the yeast NAD +-dependent histone deacetylase Sir2 regulates lifespan in yeast. While the Sirtuin family of protein deacetylases has been intensively studied in many model systems and is definitively linked to aging, the enzymes responsible for protein acetylation, protein acetyltransferases (KATs), have not received a similar level of attention. However, a series of recent studies have directly explored the role of specific KATs in aging. These studies have shown that modulation of KAT activity can influence cellular pathways important for aging and directly effect organismal lifespan.

The role of NAD and NAD precursors on longevity and lifespan modulation in the budding yeast, Saccharomyces cerevisiae

“…Studies on yeast S. cerevisiae lifespan extension have continuously pointed to Sirtuin activity, calorie response, and general cell redox balance (Nagarajan and Parthun 2020 ; Vatner, et al 2020 ). This however excuses the continuous changing state of NAD which activates or inhibits Sir2, resulting in downstream changes on aging and lifespan related conditions (McCleary and Rine 2017 ).…”

The Mechanistic Roles of Sirtuins in Breast and Prostate Cancer

“…By virtue of the above enzymatic functions, mammalian sirtuins are involved in a myriad of biological processes, including apoptosis, proliferation, differentiation, epithelial-mesenchymal transition (EMT), aging, DNA repair, senescence, viability, survival, and stress response, among other biological functions [ 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. Thus, deregulation of sirtuins can be involved in perturbations found in metabolic disorders and cancer.…”