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Proposed mechanisms of vitamin D deficiency in skeletal muscle atrophy

Deficiency leads to raised muscle protein breakdown via the ubiquitin-proteasomal pathway (UPP) and autophagy and upregulation of AMPK and members of the renin-angiotensin system. Whilst unclear, low vitamin D states may lead to impaired mitochondrial function and increased adiposity in muscle. Permanent withdrawal from the cell cycle (senescence) is a key phenomenon in aging, and the vitamin D/VDR axis has regulatory control. Abbreviations: 25(OH)D3, 25-hydroxyvitamin D; AMPK, 5′ adenosine monophosphate-activated protein kinase; SASP, senescence associated-secretory phenotype; Ca2+, calcium ion; FFA, free fatty acids; PPARγ, peroxisome proliferator-activated receptor gamma. (Source: Bollen SE, Bass JJ, Fujita S, Wilkinson D, Hewison M, Atherton PJ. The Vitamin D/vitamin D receptor (VDR) axis in muscle atrophy and sarcopenia. Cell Signal 2022;96:110355. Creative Commons Attribution [CC BY] license, creativecommons.org/licenses/by/4.0.)