Bases celulares del envejecimiento en colon y páncreaspapel del tratamiento con melatonina

Resum

Evidence for aging-induced functional changes in colon and the mechanisms underlying those changes is lacking. This study is aimed: 1.- To characerize the role of mucosal and submucosal layers on the control of colonic motility and the effects of aging and melatonin treatment in colonic motor patterns. 2.- To study age-related changes in markers of oxidative stress, immflammation and apoptosis, and alterations of mitochondria status and its role as energetic support. 3.- To determine whether neurodegenerative diseases such as Parkinson's disease develops early colonic dysfunctions that could be used as biomarkers for early diagnostic. 4.- To know age-associated changes in the polarization of intracellular calcium signalling and its propagation as calcium wave in the pancreas. The results of this thesis allow us to conclude that: 1.- Mucosa and submucosa layers should be considered as players in the control of colonic motility. Aging is associated to a decrease in myogenic and subtle alterations in neurogenic contractions, alterations of ca2 signalling and m-Tor over-expression that translates into changes on the speed and progression of the peristaltic waves. Melatonin treatment ameliorates these age-related changes. 2.- Melatonin effects are related to the normalizations of markers for oxidative stress, inflammation and apoptosis and improves mitochondria function. 3.- The animal model of Parkinson�s disease does not develop any colonic dysfunction that could be used as biomarker. 4.- Aging alters the polarized Ca2+ signal in pancreatic acini due to changes in mitochondria function an modifications of acidic Ca2+ stores and ryanodine receptors.