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This study examined the impact of Akt2 ablation on life span and cardiac aging as well as the mechanisms involved with a focus on autophagy and mitochondrial integrity. Cardiac geometry, contractile, and intracellular Ca<jats:sup>2+<\/jats:sup> properties were evaluated using echocardiography, IonOptix<jats:sup>\u00ae<\/jats:sup> edge\u2010detection and fura\u20102 techniques. Levels of Sirt1, mitochondrial integrity, autophagy, and mitophagy markers were evaluated using Western blot. Our results revealed that Akt2 ablation prolonged life span (by 9.1%) and alleviated aging (24\u00a0months)\u2010induced unfavorable changes in myocardial function and intracellular Ca<jats:sup>2+<\/jats:sup> handling (<jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>2a oxidation) albeit with more pronounced cardiac hypertrophy (58.1%, 47.8%, and 14.5% rises in heart weight, wall thickness, and cardiomyocyte cross\u2010sectional area). Aging downregulated levels of Sirt1, increased phosphorylation of Akt, and the nuclear transcriptional factor Foxo1, as well as facilitated acetylation of Foxo1, the effects of which (except Sirt1 and Foxo1 acetylation) were significantly attenuated or negated by Akt2 ablation. Advanced aging disturbed autophagy, mitophagy, and mitochondrial integrity as evidenced by increased p62, decreased levels of beclin\u20101, Atg7, <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>3B, <jats:styled-content style=\"fixed-case\">BNIP<\/jats:styled-content>3, <jats:styled-content style=\"fixed-case\">PTEN<\/jats:styled-content>\u2010induced putative kinase 1 (<jats:styled-content style=\"fixed-case\">PINK<\/jats:styled-content>1), Parkin, <jats:styled-content style=\"fixed-case\">UCP<\/jats:styled-content>\u20102, <jats:styled-content style=\"fixed-case\">PGC<\/jats:styled-content>\u20101\u03b1, and aconitase activity, the effects of which were reversed by Akt2 ablation. Aging\u2010induced cardiomyocyte contractile dysfunction and loss of mitophagy were improved by rapamycin and the Sirt1 activator <jats:styled-content style=\"fixed-case\">SRT<\/jats:styled-content>1720. Activation of Akt using insulin or Parkin deficiency prevented <jats:styled-content style=\"fixed-case\">SRT<\/jats:styled-content>1720\u2010induced beneficial effects against aging. In conclusion, our data indicate that Akt2 ablation protects against cardiac aging through restored Foxo1\u2010related autophagy and mitochondrial integrity.<\/jats:p>","DOI":"10.1111\/acel.12616","type":"journal-article","created":{"date-parts":[[2017,7,6]],"date-time":"2017-07-06T00:08:54Z","timestamp":1499299734000},"page":"976-987","source":"Crossref","is-referenced-by-count":119,"title":["Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: role of Sirt1\u2010mediated autophagy regulation"],"prefix":"10.1111","volume":"16","author":[{"given":"Jun","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Cardiology and Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai 200032 China"},{"name":"Center for Cardiovascular Research and Integrative Medicine School of Pharmacy University of Wyoming Laramie WY 82071 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Yang","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and Integrative Medicine School of Pharmacy University of Wyoming Laramie WY 82071 USA"},{"name":"Department of Anesthesiology Xi'an Children Hospital Xi'an 710003 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai 200032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xihui","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and Integrative Medicine School of Pharmacy University of Wyoming Laramie WY 82071 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asli F.","family":"Ceylan","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research and Integrative Medicine School of Pharmacy University of Wyoming Laramie WY 82071 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Animal Sciences University of Wyoming Laramie WY 82071 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Xijing Hospital Fourth Military Medical University Xi'an 710032 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology and Shanghai Institute of Cardiovascular Diseases Zhongshan Hospital Fudan University Shanghai 200032 China"},{"name":"Center for Cardiovascular Research and Integrative Medicine School of Pharmacy University of Wyoming Laramie WY 82071 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2009.00469.x"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.11.010"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01071.2006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4921"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.292.5522.1728"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.1.3.2017"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2012-0119"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.823799"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12171"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2014.12.004"},{"key":"e_1_2_8_12_1","first-page":"2972","article-title":"The endoplasmic reticulum\u2010mitochondria interface is perturbed in PARK2 knockout mice and patients with PARK2 mutations","volume":"25","author":"Gautier CA","year":"2016","journal-title":"Hum. 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