{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:58:50Z","timestamp":1786481930426,"version":"build-2736575974"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T00:00:00Z","timestamp":1674518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R00 AG037574"],"award-info":[{"award-number":["R00 AG037574"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG038072"],"award-info":[{"award-number":["P30 AG038072"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016420","name":"California Walnut Commission","doi-asserted-by":"publisher","award":["no number assigned"],"award-info":[{"award-number":["no number assigned"]}],"id":[{"id":"10.13039\/100016420","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 GM007288"],"award-info":[{"award-number":["T32 GM007288"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA013330"],"award-info":[{"award-number":["P30 CA013330"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Evidence continues to accrue that aging and its diseases can be delayed by pharmacologic and dietary strategies that target the underlying hallmarks of the aging process. However, identifying simple, safe, and effective dietary strategies involving the incorporation of whole foods that may confer some protection against the aging process is also needed. Recent observational studies have suggested that nut consumption can reduce mortality risk in humans. Among these, walnuts are particularly intriguing, given their high content of n-3 fatty acids, fiber, and antioxidant and anti-inflammatory compounds. To this end, 12-month-old male CB6F1 mice were provided either a defined control low-fat diet (LFD), a control high-fat diet (HFD), or an isocaloric HFD containing 7.67% walnuts by weight (HFD + W), and measures of healthspan and related biochemical markers (n = 10\u201319 per group) as well as survival (n = 20 per group) were monitored. Mice provided the HFD or HFD + W demonstrated marked weight gain, but walnuts lowered baseline glucose (p &lt; 0.05) and tended to temper the effects of HFD on liver weight gain (p &lt; 0.05) and insulin tolerance (p = 0.1). Additional assays suggested a beneficial effect on some indicators of health with walnut supplementation, including preservation of exercise capacity and improved short-term working memory, as determined by Y maze (p = 0.02). However, no effect was observed via any diet on inflammatory markers, antioxidant capacity, or survival (p = 0.2). Ingenuity Pathway Analysis of the hippocampal transcriptome identified two processes predicted to be affected by walnuts and potentially linked to cognitive function, including estrogen signaling and lipid metabolism, with changes in the latter confirmed by lipidomic analysis. In summary, while walnuts did not significantly improve survival on a HFD, they tended to preserve features of healthspan in the context of a metabolic stressor with aging.<\/jats:p>","DOI":"10.3390\/ijms24032314","type":"journal-article","created":{"date-parts":[[2023,1,25]],"date-time":"2023-01-25T03:53:18Z","timestamp":1674618798000},"page":"2314","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dietary Walnuts Preserve Aspects of Health Span and Alter the Hippocampal Lipidome in Aged High-Fat Diet-Fed Mice"],"prefix":"10.3390","volume":"24","author":[{"given":"Ardijana","family":"Novaj","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3596-1584","authenticated-orcid":false,"given":"Matthew G.","family":"Engel","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaonan","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-6345","authenticated-orcid":false,"given":"Yam","family":"Amir","sequence":"additional","affiliation":[{"name":"Department of Human Biology, University of Haifa, Haifa 3498838, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6895-3607","authenticated-orcid":false,"given":"Gil","family":"Atzmon","sequence":"additional","affiliation":[{"name":"Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Human Biology, University of Haifa, Haifa 3498838, Israel"},{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek M.","family":"Huffman","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Institute for Aging Research, Albert Einstein College of Medicine, Bronx, NY 10461, USA"},{"name":"Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.2337\/db11-1300","article-title":"The critical role of metabolic pathways in aging","volume":"61","author":"Barzilai","year":"2012","journal-title":"Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e12898","DOI":"10.1111\/acel.12898","article-title":"Acarbose improves health and lifespan in aging HET3 mice","volume":"18","author":"Harrison","year":"2019","journal-title":"Aging Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ebiom.2016.11.038","article-title":"NIA Interventions Testing Program: Investigating Putative Aging Intervention Agents in a Genetically Heterogeneous Mouse Model","volume":"21","author":"Nadon","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nature08221","article-title":"Rapamycin fed late in life extends lifespan in genetically heterogeneous mice","volume":"460","author":"Harrison","year":"2009","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/s41467-017-00178-3","article-title":"Every-other-day feeding extends lifespan but fails to delay many symptoms of aging in mice","volume":"8","author":"Xie","year":"2017","journal-title":"Nat. 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