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Figure 1. Acetyltransferases and deacetylases in the regulation of acetylation and deacetylation through acetyl-CoA and NAD⁺. Diets, physical activity, and fasting influence the levels of acetyl-coenzyme A (acetyl-CoA) and NAD⁺, which modulate the activities of acetyltransferases and deacetylases, mediating acetylation and deacetylation, respectively. This is also interdependently regulated by one another, highlighting the intricate crosstalk between acetyltransferases and deacetylases in maintaining cellular homeostasis. Pathological conditions (e.g., cardiometabolic disease, cancer, and aging) and other factors (e.g., post-translational modifications, genetic, epigenetic, epitranscriptomic, and environmental factors) also impact the enzymatic activities of these proteins. Additionally, acetyl-CoA can drive non-enzymatic acetylation. Acetylation regulates diverse cellular processes, including transcription, epigenetics, DNA damage repair, proliferation, cell death, cell cycle progression, autophagy, cellular metabolism, and inflammatory responses. This regulation occurs through the control of signal transduction, subcellular localization, protein stability, catalytic activity, and protein-protein interactions. Collectively, these processes underscore the essential role of acetyltransferase-mediated acetylation and deacetylase-mediated deacetylation in maintaining healthy longevity or contributing to pathological conditions, such as cardiometabolic diseases, neurodegenerative disorders, and aging.