The interest on ageing & stress has led us to foccus on patterns of expression in human cells and tissues. Stress-induced cell senescence mimicks replicative senescence of cells and is known to result from the action of a very limited number of physical or chemical agents. Recently, we added copper as one new such agent, and are now searching specific mechanisms involved, which may underlie copper related human disorders. Reproductive ageing presents a very peculiar aspect of human ageing. In fact, whereas middle aged males evidence age-related deterioration of the penile structure and vascular remodelling (as reduced smooth muscle cells and enhanced lipid cells deposition in the corpus cavernosum and VEGF receptor variation), the reduced antioxidant protection offered to oocytes by the surrounding cumulus cells is already noticed in younger females and associates to reduced number of successful pregnancies. Ageing thus imparts an oxidative stress upon cells which may be due to enhanced protein carbonylation, a point under investigation. Specific conditions impinging on stress receptors, as melanocortin-5 receptor, start a transductive process which activates cAMP/PKA and MAPK pathways. An unexpected lypolitic effect recently observed, became a point of interest. IMAGE: c-myc tagged melanocortin 5 receptor (green) and Con-A (red)in HeLa cells. Mol Cell Endoc, 2009 Future research goals: While exploring mechanisms that make copper induce cell senescence, we are now extending the range of oxidative stress regulation of human oocytes along reproductive ageing, through a major grant from an international pharmaceutical company. In addition, we are including the study to oocyte derived growth factors which work as cumulus oophorus cells modulators. To explore further the atherosclerosis-prone high fat diet effect upon the rat corpus cavernosum, we are testing the use of antioxidants and their putative targets or modulators. To examine the role of carbonylated proteins as intermediates in the modulation of metal induced oxidative stress on human fibroblasts and enlarge the prospects in ageing cell research, we are using now a human T cell line. The lypolitic effect under stressful conditions that was found is now being explored, employing a human adipose cell line (SGBS). Selected References: Tomada N, Tomada I, Botelho F, Cruz F, Vendeira P. (2011) Are all metabolic syndrome components responsible for penile hemodynamics impairment in patients with erectile dysfunction? The role of body fat mass assessment. J Sex Med. 8:831-839. Tomada I, Tomada N, Almeida H, Neves D. (2011) Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1-eNOS axis. AGE 2011 Nov 4 [Epub ahead of print], doi:10.1007/s11357-011-9328-z Tomada, I, Tomada, N, Almeida, H, and Neves, D (2011) Energy restriction and exercise modulate Angiopoietins and Vascular Endothelial Growth Factor expression in cavernous tissue of high-fat fed rat. Asian J Androl Matos, L, Gouveia, A, and Almeida, H (2011) Copper ability to induce premature senescence in human fibroblasts. AGE. Figueiredo A, Cordeiro AL, Tomada N, Tomada I, Rodrigues A, Gouveia A, Neves D (2011) Real-time PCR study of Ang1, Ang2, Tie-2, VEGF and KDR expression in human erectile tissue during aging. J Sex Med 8(5):1341-51. N. Tomada, I. Tomada, P, Vendeira, F. Cruz, D. Neves (2010) Characterization of VEGF and Angiopoietins expression in human corpus cavernosum during aging. J. Sex. Med. 7 (4): 1410-1418 Rodrigues AR, Pignatelli D, Almeida H, Gouveia AM (2009) Melanocortin 5 receptor activates ERK1/2 through a PI3K-regulated signaling mechanism. Molecular and Cellular Endocrinology, 303(1-2):74-81. L. Matos, D. Stevenson, F. Gomes, J.L. Silva-Carvalho, H. Almeida (2009) Superoxide Dismutase expression in human cumulus oophorus cells. Mol Hum Reprod. 15 (7): 411-419

Ageing and Stress