{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T19:14:43Z","timestamp":1789845283567,"version":"4.0.1"},"reference-count":220,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T00:00:00Z","timestamp":1636502400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002923","name":"National Scientific and Technical Research Council","doi-asserted-by":"publisher","award":["PIP 11220150100267CO"],"award-info":[{"award-number":["PIP 11220150100267CO"]}],"id":[{"id":"10.13039\/501100002923","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2015 2337"],"award-info":[{"award-number":["PICT 2015 2337"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2018 1221"],"award-info":[{"award-number":["PICT 2018 1221"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003074","name":"Agencia Nacional de Promoci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2017 1327"],"award-info":[{"award-number":["PICT 2017 1327"]}],"id":[{"id":"10.13039\/501100003074","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005363","name":"University of Buenos Aires","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/501100005363","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundaci\u00f3n Roemmers","award":["MEM-SPR-MBF"],"award-info":[{"award-number":["MEM-SPR-MBF"]}]},{"DOI":"10.13039\/501100010413","name":"Fundaci\u00f3n Ren\u00e9 Bar\u00f3n","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/501100010413","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003033","name":"Ministry of Science, Technology and Productive Innovation","doi-asserted-by":"publisher","award":["."],"award-info":[{"award-number":["."]}],"id":[{"id":"10.13039\/501100003033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["NIA R21-AG062985"],"award-info":[{"award-number":["NIA R21-AG062985"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000041","name":"American Diabetes Association","doi-asserted-by":"publisher","award":["ADA 1-19-IBS-126"],"award-info":[{"award-number":["ADA 1-19-IBS-126"]}],"id":[{"id":"10.13039\/100000041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The evolutionary theory of aging supports a trade-off relationship between reproduction and aging. Aging of the male reproductive system primarily affects the testes, leading to a decrease in the levels of sexual hormones, alterations in sperm quality and production, and a decline in fertility that does not necessarily involve a complete cessation of spermatogenesis. Inflammation, oxidation, and apoptosis are events considered as predictors of pathogenesis and the development of age-related diseases that are frequently observed in aged testes. Although the molecular mechanisms are still poorly understood, accumulating evidence points toward pro-inflammatory molecules and reactive oxygen species as primary contributing factors for testicular aging. However, the real impact of aging-related testicular alterations on fertility, reproductive health, and life span is far from being fully revealed. This work discusses the current knowledge on the impact of aging in the testis, particularly of aging-related dysregulated inflammation and oxidative damage on the functioning of its different cell populations. More interestingly, this review covers the potential benefits of anti-aging interventions and therapies using either pharmacological compounds (such as non-selective non-steroidal anti-inflammatory medication) or more natural alternatives (such as various nutraceuticals or even probiotics) that exhibit anti-inflammatory, antioxidant, and anti-apoptotic properties. Some of these are currently being investigated or are already in clinical use to delay or prevent testicular aging.<\/jats:p>","DOI":"10.3390\/cells10113114","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T09:19:21Z","timestamp":1636535961000},"page":"3114","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Hallmarks of Testicular Aging: The Challenge of Anti-Inflammatory and Antioxidant Therapies Using Natural and\/or Pharmacological Compounds to Improve the Physiopathological Status of the Aged Male Gonad"],"prefix":"10.3390","volume":"10","author":[{"given":"Mar\u00eda Eugenia","family":"Matzkin","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, CONICET, Ciudad de Buenos Aires C1428ADN, Argentina"},{"name":"Departamento de Bioqu\u00edmica Humana, C\u00e1tedra I, Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires C1121ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo Sa\u00fal","family":"Calandra","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, CONICET, Ciudad de Buenos Aires C1428ADN, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soledad Paola","family":"Rossi","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, CONICET, Ciudad de Buenos Aires C1428ADN, Argentina"},{"name":"Departamento de Bioqu\u00edmica Humana, C\u00e1tedra I, Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires C1121ABG, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-557X","authenticated-orcid":false,"given":"Andrzej","family":"Bartke","sequence":"additional","affiliation":[{"name":"Geriatrics Research, Department of Internal Medicine, School of Medicine, Southern Illinois University, Springfield, IL 62794, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3847-6245","authenticated-orcid":false,"given":"M\u00f3nica Beatriz","family":"Frungieri","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda y Medicina Experimental, CONICET, Ciudad de Buenos Aires C1428ADN, Argentina"},{"name":"C\u00e1tedra de Qu\u00edmica, Ciclo B\u00e1sico Com\u00fan, Universidad de Buenos Aires, Ciudad de Buenos Aires C1405CAE, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1016\/S0531-5565(00)00159-5","article-title":"Aging of the male reproductive system","volume":"35","author":"Hermann","year":"2000","journal-title":"Exp. 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