{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:43:47Z","timestamp":1793331827530,"version":"4.5.0"},"reference-count":36,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T00:00:00Z","timestamp":1667433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Aging","award":["5P01AG001751"],"award-info":[{"award-number":["5P01AG001751"]}]},{"name":"National Institute of Aging","award":["5T32HL007028"],"award-info":[{"award-number":["5T32HL007028"]}]},{"name":"National Heart, Lung, Blood Institute","award":["5P01AG001751"],"award-info":[{"award-number":["5P01AG001751"]}]},{"name":"National Heart, Lung, Blood Institute","award":["5T32HL007028"],"award-info":[{"award-number":["5T32HL007028"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Aging and poor diet are independent risk factors for heart disease, but the impact of high-sucrose (HS) consumption in the aging heart is understudied. Aging leads to impairments in mitochondrial function that result in muscle dysfunction (e.g., cardiac remodeling and sarcopenia). We tested whether HS diet (60%kcal sucrose) would accelerate muscle dysfunction in 24-month-old male CB6F1 mice. By week 1 on HS diet, mice developed significant cardiac hypertrophy compared to age-matched chow-fed controls. The increased weight of the heart persisted throughout the 4-week treatment, while body weight and strength declined more rapidly than controls. We then tested whether HS diet could worsen cardiac dysfunction in old mice and if the mitochondrial-targeted drug, elamipretide (ELAM), could prevent the diet-induced effect. Old and young mice were treated with either ELAM or saline as a control for 2 weeks, and provided with HS diet or chow on the last week. As demonstrated in the previous experiment, old mice had age-related cardiac hypertrophy that worsened after one week on HS and was prevented by ELAM treatment, while the HS diet had no detectable effect on hypertrophy in the young mice. As expected, mitochondrial respiration and reactive oxygen species (ROS) production were altered by age, but were not significantly affected by HS diet or ELAM. Our findings highlight the vulnerability of the aged heart to HS diet that can be prevented by systemic targeting of the mitochondria with ELAM.<\/jats:p>","DOI":"10.3390\/nu14214645","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T04:00:51Z","timestamp":1667534451000},"page":"4645","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Aging Increases Susceptibility to Develop Cardiac Hypertrophy following High Sugar Consumption"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2833-6492","authenticated-orcid":false,"given":"Ana P.","family":"Valencia","sequence":"first","affiliation":[{"name":"Department of Radiology, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Whitson","sequence":"additional","affiliation":[{"name":"Department of Biology, High Point University, High Point, NC 27268, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shari","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Metabolism, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leon","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Arizona College of Osteopathic Medicine, Midwestern University, Glendale, AZ 85308, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura J.","family":"den Hartigh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Metabolism, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Rabinovitch","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Marcinek","sequence":"additional","affiliation":[{"name":"Department of Radiology, University of Washington, Seattle, WA 98109, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1001\/jamainternmed.2013.13563","article-title":"Added sugar intake and cardiovascular diseases mortality among US adults","volume":"174","author":"Yang","year":"2014","journal-title":"JAMA Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"DeChristopher, L.R., Auerbach, B.J., and Tucker, K.L. (2020). High fructose corn syrup, excess-free-fructose, and risk of coronary heart disease among African Americans\u2014The Jackson Heart Study. BMC Nutr., 6.","DOI":"10.1186\/s40795-020-00396-x"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.cmet.2020.05.012","article-title":"Deletion of Fructokinase in the Liver or in the Intestine Reveals Differential Effects on Sugar-Induced Metabolic Dysfunction","volume":"32","author":"Orlicky","year":"2020","journal-title":"Cell Metab."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1038\/ncomms3434","article-title":"Endogenous fructose production and metabolism in the liver contributes to the development of metabolic syndrome","volume":"4","author":"Lanaspa","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"a025148","DOI":"10.1101\/cshperspect.a025148","article-title":"The Aging Heart","volume":"5","author":"Chiao","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e55513","DOI":"10.7554\/eLife.55513","article-title":"Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice","volume":"9","author":"Chiao","year":"2020","journal-title":"eLife"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e13213","DOI":"10.1111\/acel.13213","article-title":"SS-31 and NMN: Two paths to improve metabolism and function in aged hearts","volume":"19","author":"Whitson","year":"2020","journal-title":"Aging Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1111\/bph.12468","article-title":"Targeting mitochondrial cardiolipin and the cytochrome c\/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis","volume":"171","author":"Birk","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_9","first-page":"4869","article-title":"High fructose causes cardiac hypertrophy via mitochondrial signaling pathway","volume":"8","author":"Zhang","year":"2016","journal-title":"Am. J. Transl. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"9464","DOI":"10.1038\/s41598-018-27788-1","article-title":"Amelioration of High Fructose-Induced Cardiac Hypertrophy by Naringin","volume":"8","author":"Park","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"H125","DOI":"10.1152\/ajpheart.00199.2010","article-title":"A high-fructose diet worsens eccentric left ventricular hypertrophy in experimental volume overload","volume":"300","author":"Lachance","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"H1853","DOI":"10.1152\/ajpheart.00544.2007","article-title":"Deleterious effects of sugar and protective effects of starch on cardiac remodeling, contractile dysfunction, and mortality in response to pressure overload","volume":"293","author":"Chess","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/rco2.33","article-title":"Functional recovery from eccentric injury is maintained in sarcopenic mouse muscle","volume":"4","author":"Valencia","year":"2021","journal-title":"JCSM Rapid Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"15363","DOI":"10.1073\/pnas.2002250117","article-title":"Mitochondrial protein interaction landscape of SS-31","volume":"117","author":"Chavez","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1056\/NEJM199005313222203","article-title":"Prognostic implications of echocardiographically determined left ventricular mass in the Framingham Heart Study","volume":"322","author":"Levy","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"345","DOI":"10.7326\/0003-4819-114-5-345","article-title":"Relation of left ventricular mass and geometry to morbidity and mortality in uncomplicated essential hypertension","volume":"114","author":"Koren","year":"1991","journal-title":"Ann. Intern. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"99740","DOI":"10.18632\/oncotarget.20763","article-title":"NLRP3-inflammasome inhibition prevents high fat and high sugar diets-induced heart damage through autophagy induction","volume":"8","author":"Pavillard","year":"2017","journal-title":"Oncotarget"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1007\/s12035-017-0518-2","article-title":"Short-Term Fructose Feeding Induces Inflammation and Oxidative Stress in the Hippocampus of Young and Adult Rats","volume":"55","author":"Cigliano","year":"2018","journal-title":"Mol. Neurobiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e019948","DOI":"10.1161\/JAHA.120.019948","article-title":"Effects of Aging on Cardiac Oxidative Stress and Transcriptional Changes in Pathways of Reactive Oxygen Species Generation and Clearance","volume":"10","author":"Rizvi","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1016\/j.kint.2016.10.036","article-title":"The mitochondrial-targeted peptide, SS-31, improves glomerular architecture in mice of advanced age","volume":"91","author":"Sweetwyne","year":"2017","journal-title":"Kidney Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/acel.12102","article-title":"Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice","volume":"12","author":"Siegel","year":"2013","journal-title":"Aging Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"935","DOI":"10.2174\/15665240113139990049","article-title":"Mitochondria-targeted antioxidant peptide SS31 protects the retinas of diabetic rats","volume":"13","author":"Huang","year":"2013","journal-title":"Curr. Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s11306-014-0716-0","article-title":"Metabolic fate of fructose in human adipocytes: A targeted","volume":"11","author":"Varma","year":"2015","journal-title":"Metabolomics"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1038\/ncomms2537","article-title":"De novo lipogenesis in human fat and liver is linked to ChREBP-\u03b2 and metabolic health","volume":"4","author":"Eissing","year":"2013","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1172\/JCI37385","article-title":"Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight\/obese humans","volume":"119","author":"Stanhope","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4246","DOI":"10.1016\/j.clnu.2021.01.026","article-title":"Effect of a high fructose diet on metabolic parameters in carriers for hereditary fructose intolerance","volume":"40","author":"Debray","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/j.cmet.2021.09.010","article-title":"Molecular aspects of fructose metabolism and metabolic disease","volume":"33","author":"Herman","year":"2021","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.cmet.2019.09.003","article-title":"Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins","volume":"30","author":"Softic","year":"2019","journal-title":"Cell Metab."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1055\/s-0028-1096782","article-title":"Fructose induced depletion of liver adenine nucleotides in man","volume":"3","author":"Bode","year":"1971","journal-title":"Horm. Metab. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kim, I.Y., Ye, B.M., Kim, M.J., Kim, S.R., Lee, D.W., Kim, H.J., Rhee, H., Song, S.H., Seong, E.Y., and Lee, S.B. (2021). Association between serum uric acid and left ventricular hypertrophy\/left ventricular diastolic dysfunction in patients with chronic kidney disease. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251333"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1111\/j.1523-1755.2004.00484.x","article-title":"The impact of serum uric acid on cardiovascular outcomes in the LIFE study","volume":"65","author":"Alderman","year":"2004","journal-title":"Kidney Int."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1161\/ATVBAHA.116.308010","article-title":"Effects of Sugar-Sweetened Beverage Consumption on Microvascular and Macrovascular Function in a Healthy Population","volume":"37","author":"Loader","year":"2017","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3945\/ajcn.112.057331","article-title":"Dietary fructose induces endotoxemia and hepatic injury in calorically controlled primates","volume":"98","author":"Kavanagh","year":"2013","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7364","DOI":"10.1038\/s41598-021-86797-9","article-title":"Female mice are more prone to develop an addictive-like phenotype for sugar consumption","volume":"11","author":"Wei","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1136\/heartjnl-2015-308769","article-title":"Sex differences in cardiovascular ageing","volume":"102","author":"Merz","year":"2016","journal-title":"Heart"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.exger.2015.11.011","article-title":"The presence of the ovary prevents hepatic mitochondrial oxidative stress in young and aged female mice through glutathione peroxidase 1","volume":"73","author":"Valencia","year":"2016","journal-title":"Exp. Gerontol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/21\/4645\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:10:19Z","timestamp":1760145019000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/21\/4645"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,3]]},"references-count":36,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["nu14214645"],"URL":"https:\/\/doi.org\/10.3390\/nu14214645","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,3]]}}}