{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:57:54Z","timestamp":1773925074861,"version":"3.50.1"},"reference-count":41,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T00:00:00Z","timestamp":1561075200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDB\/BBB-BQB\/3804\/2014"],"award-info":[{"award-number":["PTDB\/BBB-BQB\/3804\/2014"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/BIM\/04501\/2013"],"award-info":[{"award-number":["UID\/BIM\/04501\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007628"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007628"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["SFRH\/BPD\/123155\/2016"],"award-info":[{"award-number":["SFRH\/BPD\/123155\/2016"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Integrated Programme of SR&amp;TD","award":["CENTRO-01-0145-FEDER-000003"],"award-info":[{"award-number":["CENTRO-01-0145-FEDER-000003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Understanding how age affects fertility becomes increasingly relevant as couples delay childbearing toward later stages of their lives. While the influence of maternal age on fertility is well established, the impact of paternal age is poorly characterized. Thus, this study aimed to understand the molecular mechanisms responsible for age-dependent decline in spermatozoa quality. To attain it, we evaluated the impact of male age on the activity of signaling proteins in two distinct spermatozoa populations: total spermatozoa fraction and highly motile\/viable fraction. In older men, we observed an inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) in the highly viable spermatozoa population. On the contrary, when considering the entire spermatozoa population (including defective\/immotile\/apoptotic cells) our findings support an active mTORC1 signaling pathway in older men. Additionally, total spermatozoa fractions of older men presented increased levels of apoptotic\/stress markers [e.g., cellular tumor antigen p53 (TP53)] and mitogen-activated protein kinases (MAPKs) activity. Moreover, we established that the levels of most signaling proteins analyzed were consistently and significantly altered in men older than 27 years of age. This study was the first to associate the mTOR signaling pathway with the age impact on spermatozoa quality. Additionally, we constructed a network of the sperm proteins associated with male aging, identifying TP53 as a central player in spermatozoa aging.<\/jats:p>","DOI":"10.3390\/cells8060629","type":"journal-article","created":{"date-parts":[[2019,6,21]],"date-time":"2019-06-21T11:54:31Z","timestamp":1561118071000},"page":"629","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["mTOR Signaling Pathway Regulates Sperm Quality in Older Men"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2884-3259","authenticated-orcid":false,"given":"Joana Vieira","family":"Silva","sequence":"first","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine\u2013iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Madalena","family":"Cabral","sequence":"additional","affiliation":[{"name":"COGE-Cl\u00ednica Obst\u00e9trica e Ginecol\u00f3gica de Espinho, 4500-057 Espinho, Portugal"}]},{"given":"B\u00e1rbara Regadas","family":"Correia","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine\u2013iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]},{"given":"Pedro","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine\u2013iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"},{"name":"COGE-Cl\u00ednica Obst\u00e9trica e Ginecol\u00f3gica de Espinho, 4500-057 Espinho, Portugal"}]},{"given":"M\u00e1rio","family":"Sousa","sequence":"additional","affiliation":[{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4989-5699","authenticated-orcid":false,"given":"Pedro Fontes","family":"Oliveira","sequence":"additional","affiliation":[{"name":"i3S-Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, University of Porto, 4200-135 Porto, Portugal"},{"name":"Unit for Multidisciplinary Research in Biomedicine (UMIB), Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"},{"name":"Department of Microscopy, Laboratory of Cell Biology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7459-9173","authenticated-orcid":false,"given":"Margarida","family":"Fardilha","sequence":"additional","affiliation":[{"name":"Laboratory of Signal Transduction, Department of Medical Sciences, Institute of Biomedicine\u2013iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/j.1365-2605.2005.00639.x","article-title":"Fertility rates and future population trends: Will Europe\u2019s birth rate recover or continue to decline?","volume":"29","author":"Lutz","year":"2006","journal-title":"Int. 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