Volume 4, Issue 9

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Barrientos A, . Complementary roles of mitochondrial respiration and ROS signaling on cellular aging and longevity. . 4:578-579. https://doi.org/10.18632/aging.100485

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Provider: TY - JOUR AU - Barrientos, Antoni TI - Complementary roles of mitochondrial respiration and ROS signaling on cellular aging and longevity JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100485 DO - 10.18632/aging.100485 SP - 578 EP - 579 PY - ER -

Provider: TY - JOUR AU - Barrientos, Antoni TI - Complementary roles of mitochondrial respiration and ROS signaling on cellular aging and longevity JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100485 DO - 10.18632/aging.100485 SP - 578 EP - 579 PY - AB - ER -

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Vitale G, Brugts MP, Ogliari G, Castaldi D, Fatti LM, Varewijck AJ, Lamberts SW, Monti D, Bucci L, Cevenini E, Cavagnini F, Franceschi C, Hofland LJ, et al, . Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians’ offspring. . 4:580-589. https://doi.org/10.18632/aging.100484

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Provider: TY - JOUR AU - Vitale, Giovanni AU - Brugts, Michael P AU - Ogliari, Giulia AU - Castaldi, Davide AU - Fatti, Letizia M. AU - Varewijck, Aimee J. AU - Lamberts, Steven W. AU - Monti, Daniela AU - Bucci, Laura AU - Cevenini, Elisa AU - Cavagnini, Francesco AU - Franceschi, Claudio AU - Hofland, Leo J AU - Mari, Daniela AU - Janssen, Joseph A.M.J.L. TI - Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians’ offspring JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100484 DO - 10.18632/aging.100484 SP - 580 EP - 589 PY - ER -

Provider: TY - JOUR AU - Vitale, Giovanni AU - Brugts, Michael P AU - Ogliari, Giulia AU - Castaldi, Davide AU - Fatti, Letizia M. AU - Varewijck, Aimee J. AU - Lamberts, Steven W. AU - Monti, Daniela AU - Bucci, Laura AU - Cevenini, Elisa AU - Cavagnini, Francesco AU - Franceschi, Claudio AU - Hofland, Leo J AU - Mari, Daniela AU - Janssen, Joseph A.M.J.L. TI - Low circulating IGF-I bioactivity is associated with human longevity: Findings in centenarians’ offspring JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100484 DO - 10.18632/aging.100484 SP - 580 EP - 589 PY - AB - Centenarians’ offspring represent a suitable model to study age-dependent variables (e.g. IGF-I) potentially involved in the modulation of the lifespan. The aim of the present study was to investigate the role of the IGF-I in human longevity. We evaluated circulating IGF-I bioactivity measured by an innovative IGF-I Kinase Receptor Activation (KIRA) Assay, total IGF-I, IGFBP-3, total IGF-II, insulin, glucose, HOMA2-B% and HOMA2-S% in 192 centenarians’ offspring and 80 offspring-controls of which both parents died relatively young. Both groups were well-matched for age, gender and BMI with the centenarians’ offspring. IGF-I bioactivity (p<0.01), total IGF-I (p<0.01) and the IGF-I/IGFBP-3 molar ratio (p<0.001) were significantly lower in centenarians’ offspring compared to offspring matched-controls. Serum insulin, glucose, HOMA2-B% and HOMA2-S% values were similar between both groups. In centenarians’ offspring IGF-I bioactivity was inversely associated to insulin sensitivity. In conclusion: 1) centenarians’ offspring had relatively lower circulating IGF-I bioactivity compared to offspring matched-controls; 2) IGF-I bioactivity in centenarians’ offspring was inversely related to insulin sensitivity. These data support a role of the IGF-I/insulin system in the modulation of human aging process. ER -

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Sheinerman KS, Tsivinsky VG, Crawford F, Mullan MJ, Abdullah L, Umansky SR, . Plasma microRNA biomarkers for detection of mild cognitive impairment. . 4:590-605. https://doi.org/10.18632/aging.100486

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Provider: TY - JOUR AU - Sheinerman, Kira S. AU - Tsivinsky, Vladimir G. AU - Crawford, Fiona AU - Mullan, Michael J. AU - Abdullah, Laila AU - Umansky, Samuil R. TI - Plasma microRNA biomarkers for detection of mild cognitive impairment JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100486 DO - 10.18632/aging.100486 SP - 590 EP - 605 PY - ER -

Provider: TY - JOUR AU - Sheinerman, Kira S. AU - Tsivinsky, Vladimir G. AU - Crawford, Fiona AU - Mullan, Michael J. AU - Abdullah, Laila AU - Umansky, Samuil R. TI - Plasma microRNA biomarkers for detection of mild cognitive impairment JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100486 DO - 10.18632/aging.100486 SP - 590 EP - 605 PY - AB - Early stages of many neurodegenerative diseases, such as Alzheimer's disease, vascular and frontotemporal dementia, and Parkinson's disease, are frequently associated with Mild Cognitive Impairment (MCI). A minimally invasive screening test for early detection of MCI may be used to select optimal patient groups in clinical trials, to monitor disease progression and response to treatment, and to better plan patient clinical care. Here, we examined the feasibility of using pairs of brain-enriched plasma microRNA (miRNA), at least one of which is enriched in synapses and neurites, as biomarkers that could differentiate patients with MCI from age-matched controls. The identified biomarker pairs fall into two sets: the “miR-132 family” (miR-128/miR-491-5p, miR-132/miR-491-5p and mir-874/miR-491-5p) and the “miR-134 family” (miR-134/miR-370, miR-323-3p/miR-370 and miR-382/miR-370). The area under the Receiver-Operating Characteristic curve for the differentiation of MCI from controls using these biomarker pairs is 0.91-0.95, with sensitivity and specificity at 79%-100% (miR-132 family) and 79%-95% (miR-134 family), and p < 0.001. In a separate longitudinal study, the identified miRNA biomarker pairs successfully detected MCI in majority of patients at asymptomatic stage 1-5 years prior to clinical diagnosis. The reported biomarker pairs also appear useful for detecting age-related brain changes. Further testing in a larger study is necessary for validation of these results. ER -

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Sun L, Brown R, Chen S, Zhuge Q, Su D, . Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus. . 4:606-619. https://doi.org/10.18632/aging.100487

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Provider: TY - JOUR AU - Sun, Liguang AU - Brown, Robert AU - Chen, Shande AU - Zhuge, Qichuan AU - Su, Dong-Ming TI - Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100487 DO - 10.18632/aging.100487 SP - 606 EP - 619 PY - ER -

Provider: TY - JOUR AU - Sun, Liguang AU - Brown, Robert AU - Chen, Shande AU - Zhuge, Qichuan AU - Su, Dong-Ming TI - Aging induced decline in T-lymphopoiesis is primarily dependent on status of progenitor niches in the bone marrow and thymus JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100487 DO - 10.18632/aging.100487 SP - 606 EP - 619 PY - AB - Age-related decline in the generation of T cells is associated with two primary lymphoid organs, the bone marrow (BM) and thymus. Both organs contain lympho-hematopoietic progenitor/stem cells (LPCs) and non-hematopoietic stromal/niche cells. Murine model showed this decline is not due to reduced quantities of LPCs, nor autonomous defects in LPCs, but rather defects in their niche cells. However, this viewpoint is challenged by the fact that aged BM progenitors have a myeloid skew. By grafting young wild-type (WT) BM progenitors into aged IL-7R−/− hosts, which possess WT-equivalent niches although LPCs are defect, we demonstrated that these young BM progenitors also exhibited a myeloid skew. We, further, demonstrated that aged BM progenitors, recruited by a grafted fetal thymus in the in vivo microenvironment, were able to compete with their young counterparts, although the in vitro manipulated old BM cells were not able to do so in conventional BM transplantation. Both LPCs and their niche cells inevitably get old with increasing organismal age, but aging in niche cells occurred much earlier than in LPCs by an observation in thymic T-lymphopoiesis. Therefore, the aging induced decline in competence to generate T cells is primarily dependent on status of the progenitor niche cells in the BM and thymus. ER -

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Thomas RR, Khan SM, Smigrodzki RM, Onyango IG, Dennis J, Khan OM, Portell FR, Bennett JP, . RhTFAM treatment stimulates mitochondrial oxidative metabolism and improves memory in aged mice. . 4:620-635. https://doi.org/10.18632/aging.100488

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Provider: TY - JOUR AU - Thomas, Ravindar R. AU - Khan, Shaharyar M. AU - Smigrodzki, Rafal M. AU - Onyango, Isaac G. AU - Dennis, Jameel AU - Khan, Omer M. AU - Portell, Francisco R. AU - Bennett, James P. TI - RhTFAM treatment stimulates mitochondrial oxidative metabolism and improves memory in aged mice JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100488 DO - 10.18632/aging.100488 SP - 620 EP - 635 PY - ER -

Provider: TY - JOUR AU - Thomas, Ravindar R. AU - Khan, Shaharyar M. AU - Smigrodzki, Rafal M. AU - Onyango, Isaac G. AU - Dennis, Jameel AU - Khan, Omer M. AU - Portell, Francisco R. AU - Bennett, James P. TI - RhTFAM treatment stimulates mitochondrial oxidative metabolism and improves memory in aged mice JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100488 DO - 10.18632/aging.100488 SP - 620 EP - 635 PY - AB - Mitochondrial function declines with age in postmitotic tissues such as brain, heart and skeletal muscle. Despite weekly exercise, aged mice showed substantial losses of mtDNA gene copy numbers and reductions in mtDNA gene transcription and mitobiogenesis signaling in brain and heart. We treated these mice with weekly intravenous injections of recombinant human mitochondrial transcription factor A (rhTFAM). RhTFAM treatment for one month increased mitochondrial respiration in brain, heart and muscle, POLMRT expression and mtDNA gene transcription in brain, and PGC-1 alpha mitobiogenesis signaling in heart. RhTFAM treatment reduced oxidative stress damage to brain proteins, improved memory in Morris water maze performance and increased brain protein levels of BDNF and synapsin. Microarray analysis showed co-expression of multiple Gene Ontology families in rhTFAM-treated aged brains compared to young brains. RhTFAM treatment reverses age-related memory impairments associated with loss of mitochondrial energy production in brain, increases levels of memory-related brain proteins and improves mitochondrial respiration in brain and peripheral tissues. ER -

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Dallaire A, Garand C, Paquet ER, Mitchell SJ, de Cabo R, Simard MJ, Lebel M, . Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant Caenorhabditis elegans wrn-1 reveals the importance of this microRNA in accelerated aging. . 4:636-647. https://doi.org/10.18632/aging.100489

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Provider: TY - JOUR AU - Dallaire, Alexandra AU - Garand, Chantal AU - Paquet, Eric R. AU - Mitchell, Sarah J. AU - de Cabo, Rafael AU - Simard, Martin J. AU - Lebel, Michel TI - Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant <i>Caenorhabditis elegans wrn-1</i> reveals the importance of this microRNA in accelerated aging JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100489 DO - 10.18632/aging.100489 SP - 636 EP - 647 PY - ER -

Provider: TY - JOUR AU - Dallaire, Alexandra AU - Garand, Chantal AU - Paquet, Eric R. AU - Mitchell, Sarah J. AU - de Cabo, Rafael AU - Simard, Martin J. AU - Lebel, Michel TI - Down regulation of miR-124 in both Werner syndrome DNA helicase mutant mice and mutant <i>Caenorhabditis elegans wrn-1</i> reveals the importance of this microRNA in accelerated aging JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100489 DO - 10.18632/aging.100489 SP - 636 EP - 647 PY - AB - Small non-coding microRNAs are believed to be involved in the mechanism of aging but nothing is known on the impact of microRNAs in the progeroid disorder Werner syndrome (WS). WS is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN ortholog exhibit many phenotypic features of WS, including a pro-oxidant status and a shorter mean life span. Caenorhabditis elegans (C. elegans) with a nonfunctional wrn-1 DNA helicase also exhibit a shorter life span. Thus, both models are relevant to study the expression of microRNAs involved in WS. In this study, we show that miR-124 expression is lost in the liver of Wrn helicase mutant mice. Interestingly, the expression of this conserved miR-124 in whole wrn-1 mutant worms is also significantly reduced. The loss of mir-124 in C. elegans increases reactive oxygen species formation and accumulation of the aging marker lipofuscin, reduces whole body ATP levels and results in a reduction in life span. Finally, supplementation of vitamin C normalizes the median life span of wrn-1 and mir-124 mutant worms. These results suggest that biological pathways involving WRN and miR-124 are conserved in the aging process across different species. ER -

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Agrawal A, Su H, Chen J, Osann K, Agrawal S, Gupta S, . Increased IL-21 secretion by aged CD4+T cells is associated with prolonged STAT-4 activation and CMV seropositivity. . 4:648-659. https://doi.org/10.18632/aging.100490

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Provider: TY - JOUR AU - Agrawal, Anshu AU - Su, Houfen AU - Chen, Justine AU - Osann, Kathryn AU - Agrawal, Sudhanshu AU - Gupta, Sudhir TI - Increased IL-21 secretion by aged CD4+T cells is associated with prolonged STAT-4 activation and CMV seropositivity JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100490 DO - 10.18632/aging.100490 SP - 648 EP - 659 PY - ER -

Provider: TY - JOUR AU - Agrawal, Anshu AU - Su, Houfen AU - Chen, Justine AU - Osann, Kathryn AU - Agrawal, Sudhanshu AU - Gupta, Sudhir TI - Increased IL-21 secretion by aged CD4+T cells is associated with prolonged STAT-4 activation and CMV seropositivity JO - JA - VL - 4 IS - 9 PB - SN - UR - https://doi.org/10.18632/aging.100490 DO - 10.18632/aging.100490 SP - 648 EP - 659 PY - AB - Advancing age leads to significant decline in immune functions. IL-21 is produced primarily by T follicular helper (Tfh) cells and is required for effective immune cell functions. Here we compared the induction of IL-21 in aged and young subjects. Our investigation demonstrates that CD4+T cells from healthy elderly individuals (age ≥ 65) secreted significantly higher levels of IL-21 on priming with aged and young dendritic cells (DC). Though the aged and young DCs secreted comparable levels of IL-12 on stimulation with anti-CD40 antibody and LPS, culture of DCs with aged CD4+ T cells resulted in increased production of IL-21 as compared to that with young CD4+ T cells. Further examination revealed that the response of aged naïve CD4+ T cells to IL-12 was altered, resulting in increased differentiation of aged Th cells towards Tfh cells. Investigation into the signaling mechanism suggested that phosphorylation of STAT-4 in response to IL-12 was sustained for a longer duration in aged CD4+ T cells as compared to CD4+ T cells from young subjects. Additional analysis demonstrated that increased IL-21 secretion correlated with chronic CMV infection in aged subjects. These findings indicate that chronic CMV infection alters the response of aged CD4+ T cells to IL-12 resulting in an increased secretion of IL-21 and that aging affects Tfh cell responses in humans which may contribute to age-associated inflammation and immune dysfunctions. ER -

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