D-galactose induces a mitochondrial complex I deficiency in mouse skeletal muscle: potential benefits of nutrient combination in ameliorating muscle impairment

J Med Food. 2014 Mar;17(3):357-64. doi: 10.1089/jmf.2013.2830. Epub 2014 Jan 29.


Accumulating research has shown that chronic D-galactose (D-gal) exposure induces symptoms similar to natural aging in animals. Therefore, rodents chronically exposed to D-gal are increasingly used as a model for aging and delay-of-aging pharmacological research. Mitochondrial dysfunction is thought to play a vital role in aging and age-related diseases; however, whether mitochondrial dysfunction plays a significant role in mice exposed to D-gal remains unknown. In the present study, we investigated cognitive dysfunction, locomotor activity, and mitochondrial dysfunction involved in D-gal exposure in mice. We found that D-gal exposure (125 mg/kg/day, 8 weeks) resulted in a serious impairment in grip strength in mice, whereas spatial memory and locomotor coordination remained intact. Interestingly, muscular mitochondrial complex I deficiency occurred in the skeletal muscle of mice exposed to D-gal. Mitochondrial ultrastructure abnormality was implicated as a contributing factor in D-gal-induced muscular impairment. Moreover, three combinations (A, B, and C) of nutrients applied in this study effectively reversed D-gal-induced muscular impairment. Nutrient formulas B and C were especially effective in reversing complex I dysfunction in both skeletal muscle and heart muscle. These findings suggest the following: (1) chronic exposure to D-gal first results in specific muscular impairment in mice, rather than causing general, premature aging; (2) poor skeletal muscle strength induced by D-gal might be due to the mitochondrial dysfunction caused by complex I deficiency; and (3) the nutrient complexes applied in the study attenuated the skeletal muscle impairment, most likely by improving mitochondrial function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Electron Transport Complex I / deficiency*
  • Electron Transport Complex I / metabolism
  • Female
  • Galactose / adverse effects*
  • Galactose / metabolism
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Mitochondrial Diseases / diet therapy
  • Mitochondrial Diseases / enzymology
  • Mitochondrial Diseases / etiology*
  • Mitochondrial Diseases / metabolism
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*


  • Electron Transport Complex I
  • Galactose

Supplementary concepts

  • Mitochondrial complex I deficiency