Figure 3.

Common autophagy signaling pathways shared between skeletal muscle contraction (i.e., acute exercise) and caloric restriction. Perturbations in calcium (Ca⁺⁺), adenosine monophosphate (AMP), and nicotinamide adenine dinucleotide (NAD⁺) activate calcineurin, 5′ adenosine monophosphate kinase (AMPK), and sirtuin‐1 (SIRT1), respectively. AMPK induces autophagosome formation through ULK1 while AMPK and SIRT1 act to upregulate expression of Atgs by increasing forkhead box transcription factors (FOXOs) and peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC1α) and downregulate mammalian target of rapamycin complex 1 (mTORC1). Calcineurin activation and mTORC1 inhibition activate transcription factor EB (TFEB) which activates the CLEAR (coordinated lysosomal expression and regulation) gene network and the transcription of Atgs