title: Age-related changes in mitochondrial function of mouse colonic smooth muscle: beneficial effects of melatonin.
abstract: Aging is a multifactorial process that involves biochemical, structural, and functional changes in mitochondria. The ability of melatonin to palliate the alterations induced by aging is based on its chronobiologic, antioxidant, and mitochondrial effects. There is little information about the effects of melatonin on the in situ mitochondrial network of aging cells and its physiological implications. We have studied the ability of melatonin to prevent the functional alterations of in situ mitochondria of smooth muscle cells and its impact on contractility. Mitochondrial membrane potential was recorded in isolated colonic smooth muscle cells from young mice (3 month old), aged mice (22-24-month old), and aged mice treated with melatonin (starting at 14-month age). Aging induced a partial mitochondrial depolarization in resting conditions and reduced the depolarizing response to cellular stimulation. Use of oligomycin indicated that aging enhanced the resting activity of the mitochondrial ATP synthase, whereas in young cells, the enzyme operated mainly in reverse mode. Melatonin treatment prevented all these changes. Aging reduced both spontaneous and stimulated contraction of colonic strips and shifted the metabolic dependence of contraction from mitochondria to glycolysis, as indicated the use of mitochondrial and glycolysis inhibitors. These functional alterations were also palliated by melatonin treatment. Aging effects were not related to a decrease in Ca2+ store mobilization, because this was enhanced in aged cells and restored by melatonin. In conclusion, melatonin prevents the age induced in situ mitochondrial potential alterations in smooth muscle cells and the associated changes in contractility and metabolism.
authors: Department of Physiology, Faculty of Nursing and Occupational Therapy, University of Extremadura, Cáceres, Spain.
authors: Francisco E
authors: FE
authors: Martin-Cano
authors: Cristina
authors: C
authors: Camello-Almaraz
authors: Dario
authors: D
authors: Acuña-Castroviejo
authors: Maria J
authors: MJ
authors: Pozo
authors: Pedro J
authors: PJ
authors: Camello
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D008550:Melatonin; D002118:Calcium
keywords: aging; colon; mitochondria