The AMP-activated protein kinase (AMPK) is considered a key checkpoint to ensure energy balance in both cells and organisms. AMPK is an αβγ heterotrimer controlled by allosteric regulation by AMP, ADP and ATP, auto-inhibitory features and phosphorylation, with the threonine-172 phosphorylation on the catalytic α-subunit by LKB1, CaMKKβ or Tak1 being essential for its fully activation. AMPK acts as a protective response to energy stress in numerous systems, but it is also a key player in diabetes and related metabolic diseases and cancer. Pharmacological activation of AMPK by metformin or other compounds holds a considerable potential to reverse the metabolic abnormalities associated with type 2 diabetes. In cancer, correction of the dysregulated metabolic pathway LKB1/AMPK/mTORC1 can lower the Warburg effect, suggesting AMPK as a potential target for cancer prevention and/or treatment.

In this commentary, we review recent findings that support the role and function of AMPK in normal and pathological conditions. We also discuss how the activation of AMPK by naturally occurring compounds could help to prevent the development of numerous chronic diseases contributing in such a way to the well-being of ageing population.