Volume 7, Issue 1

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Qian H, Xu X, Niklason LE, . PCH-2 regulates Caenorhabditis elegans lifespan. . 7:1-13. https://doi.org/10.18632/aging.100713

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Provider: TY - JOUR AU - Qian, Hong AU - Xu, Xiangru AU - Niklason, Laura E TI - PCH-2 regulates <i>Caenorhabditis elegans</i> lifespan JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100713 DO - 10.18632/aging.100713 SP - 1 EP - 13 PY - ER -

Provider: TY - JOUR AU - Qian, Hong AU - Xu, Xiangru AU - Niklason, Laura E TI - PCH-2 regulates <i>Caenorhabditis elegans</i> lifespan JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100713 DO - 10.18632/aging.100713 SP - 1 EP - 13 PY - AB - Components or downstream targets of many signaling pathways such as Insulin/IGF-1 and TOR, as well as genes involved in cellular metabolism and bioenergetics can extend worm lifespan 20% or more. The C. elegans gene pch-2 and its homologs, including TRIP13 in humans, have been studied for their functions in cell mitosis and meiosis, but have never been implicated in lifespan regulation. Here we show that over-expression of TRIP13 in human fibroblasts confers resistance to environmental stressors such as UV radiation and oxidative stress. Furthermore, pch-2 overexpression in C. elegans extends worm lifespan, and enhances worm survival in response to various stressors. Conversely, reducing pch-2 expression with RNAi shortens worm lifespan. Additional genetic epistasis analysis indicates that the molecular mechanism of pch-2 in worm longevity is tied to functions of the sirtuin family, implying that pch-2 is another chromatin regulator for worm longevity. These findings suggest a novel function of the pch-2 gene involved in lifespan determination ER -

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Dmitrieva RI, Revittser AV, Klukina MA, Sviryaev YV, Korostovtseva LS, Kostareva AA, Zaritskey AY, Shlyakhto EV, . Functional properties of bone marrow derived multipotent mesenchymal stromal cells are altered in heart failure patients, and could be corrected by adjustment of expansion strategies. . 7:14-25. https://doi.org/10.18632/aging.100716

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Provider: TY - JOUR AU - Dmitrieva, Renata I. AU - Revittser, Alla V. AU - Klukina, Maria A. AU - Sviryaev, Yuri V. AU - Korostovtseva, Ludmila S. AU - Kostareva, Anna A. AU - Zaritskey, Andrey Yu. AU - Shlyakhto, Evgeny V. TI - Functional properties of bone marrow derived multipotent mesenchymal stromal cells are altered in heart failure patients, and could be corrected by adjustment of expansion strategies JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100716 DO - 10.18632/aging.100716 SP - 14 EP - 25 PY - ER -

Provider: TY - JOUR AU - Dmitrieva, Renata I. AU - Revittser, Alla V. AU - Klukina, Maria A. AU - Sviryaev, Yuri V. AU - Korostovtseva, Ludmila S. AU - Kostareva, Anna A. AU - Zaritskey, Andrey Yu. AU - Shlyakhto, Evgeny V. TI - Functional properties of bone marrow derived multipotent mesenchymal stromal cells are altered in heart failure patients, and could be corrected by adjustment of expansion strategies JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100716 DO - 10.18632/aging.100716 SP - 14 EP - 25 PY - AB - Background: Bone marrow multipotent mesenchymal stromal cells (BM-MMSC) considered as a prospective substrate for cell therapy applications, however adult stem cells could be affected by donor-specific factors: age, gender, medical history. Our aim was to investigate how HF affects the functional properties of BM-MMSC. Materials and methods: BM-MMSC from 10 healthy donors (HD), and 16 donors with chronic HF were evaluated for proliferative activity, ability to differentiate, replicative senescence, expression of genes that affect regeneration and fibrosis. The effect of culturing conditions on efficiency of BM-MMSC expansion was determined. Results: HF-derived BM-MMSC demonstrated early decrease of proliferative activity and upregulation of genes that control both, regeneration and fibrosis: Tgf-β pathway, synthesis of ECM, remodeling enzymes, adhesion molecules. We assume that these effects were related to increase of frequency of myofibroblast-like CD146+/SMAα+ CFU-F in HF samples; (ii) low seeding density and hypoxia resulted in predominant purification and expansion of CD146+/SMAα- CFU-Fs. (iii) the activity of NPs system was downregulated in HF BM-MMSC; Conclusions: downregulation of NP signaling in combination with upregulation of Tgf-β pathway in BM-MMSC would result in pro-fibrotic phenotype and make these cells non-effective for therapeutic applications; the corrections in culturing strategy resulted in 23-27 increase of expansion efficiency. ER -

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Aliper AM, Csoka AB, Buzdin A, Jetka T, Roumiantsev S, Moskalev A, Zhavoronkov A, . Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells. . 7:26-37. https://doi.org/10.18632/aging.100717

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Provider: TY - JOUR AU - Aliper, Alexander M. AU - Csoka, Antonei Benjamin AU - Buzdin, Anton AU - Jetka, Tomasz AU - Roumiantsev, Sergey AU - Moskalev, Alexey AU - Zhavoronkov, Alex TI - Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100717 DO - 10.18632/aging.100717 SP - 26 EP - 37 PY - ER -

Provider: TY - JOUR AU - Aliper, Alexander M. AU - Csoka, Antonei Benjamin AU - Buzdin, Anton AU - Jetka, Tomasz AU - Roumiantsev, Sergey AU - Moskalev, Alexey AU - Zhavoronkov, Alex TI - Signaling pathway activation drift during aging: Hutchinson-Gilford Progeria Syndrome fibroblasts are comparable to normal middle-age and old-age cells JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100717 DO - 10.18632/aging.100717 SP - 26 EP - 37 PY - AB - For the past several decades, research in understanding the molecular basis of human aging has progressed significantly with the analysis of premature aging syndromes. Progerin, an altered form of lamin A, has been identified as the cause of premature aging in Hutchinson-Gilford Progeria Syndrome (HGPS), and may be a contributing causative factor in normal aging. However, the question of whether HGPS actually recapitulates the normal aging process at the cellular and organismal level, or simply mimics the aging phenotype is widely debated. In the present study we analyzed publicly available microarray datasets for fibroblasts undergoing cellular aging in culture, as well as fibroblasts derived from young, middle-age, and old-age individuals, and patients with HGPS. Using GeroScope pathway analysis and drug discovery platform we analyzed the activation states of 65 major cellular signaling pathways. Our analysis reveals that signaling pathway activation states in cells derived from chronologically young patients with HGPS strongly resemble cells taken from normal middle-aged and old individuals. This clearly indicates that HGPS may truly represent accelerated aging, rather than being just a simulacrum. Our data also points to potential pathways that could be targeted to develop drugs and drug combinations for both HGPS and normal aging. ER -

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Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, Siconolfi B, Park K, Gill TM, et al, . Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. . 7:38-52. https://doi.org/10.18632/aging.100720

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Provider: TY - JOUR AU - Thakar, Juilee AU - Mohanty, Subhasis AU - West, A. Phillip AU - Joshi, Samit R. AU - Ueda, Ikuyo AU - Wilson, Jean AU - Meng, Hailong AU - Blevins, Tamara P. AU - Tsang, Sui AU - Trentalange, Mark AU - Siconolfi, Barbara AU - Park, Koonam AU - Gill, Thomas M. AU - Belshe, Robert B. AU - Kaech, Susan M. AU - Shadel, Gerald S. AU - Kleinstein, Steven H. AU - Shaw, Albert C. TI - Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100720 DO - 10.18632/aging.100720 SP - 38 EP - 52 PY - ER -

Provider: TY - JOUR AU - Thakar, Juilee AU - Mohanty, Subhasis AU - West, A. Phillip AU - Joshi, Samit R. AU - Ueda, Ikuyo AU - Wilson, Jean AU - Meng, Hailong AU - Blevins, Tamara P. AU - Tsang, Sui AU - Trentalange, Mark AU - Siconolfi, Barbara AU - Park, Koonam AU - Gill, Thomas M. AU - Belshe, Robert B. AU - Kaech, Susan M. AU - Shadel, Gerald S. AU - Kleinstein, Steven H. AU - Shaw, Albert C. TI - Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100720 DO - 10.18632/aging.100720 SP - 38 EP - 52 PY - AB - To elucidate gene expression pathways underlying age-associated impairment in influenza vaccine response, we screened young (age 21-30) and older (age ≥65) adults receiving influenza vaccine in two consecutive seasons and identified those with strong or absent response to vaccine, including a subset of older adults meeting criteria for frailty. PBMCs obtained prior to vaccination (Day 0) and at day 2 or 4, day 7 and day 28 post-vaccine were subjected to gene expression microarray analysis. We defined a response signature and also detected induction of a type I interferon response at day 2 and a plasma cell signature at day 7 post-vaccine in young responders. The response signature was dysregulated in older adults, with the plasma cell signature induced at day 2, and was never induced in frail subjects (who were all non-responders). We also identified a mitochondrial signature in young vaccine responders containing genes mediating mitochondrial biogenesis and oxidative phosphorylation that was consistent in two different vaccine seasons and verified by analyses of mitochondrial content and protein expression. These results represent the first genome-wide transcriptional profiling analysis of age-associated dynamics following influenza vaccination, and implicate changes in mitochondrial biogenesis and function as a critical factor in human vaccine responsiveness. ER -

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Landis GN, Salomon MP, Keroles D, Brookes N, Sekimura T, Tower J, . The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila. . 7:53-69. https://doi.org/10.18632/aging.100721

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Provider: TY - JOUR AU - Landis, Gary N. AU - Salomon, Matthew P. AU - Keroles, Daniel AU - Brookes, Nicholas AU - Sekimura, Troy AU - Tower, John TI - The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100721 DO - 10.18632/aging.100721 SP - 53 EP - 69 PY - ER -

Provider: TY - JOUR AU - Landis, Gary N. AU - Salomon, Matthew P. AU - Keroles, Daniel AU - Brookes, Nicholas AU - Sekimura, Troy AU - Tower, John TI - The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100721 DO - 10.18632/aging.100721 SP - 53 EP - 69 PY - AB - Mating causes decreased life span in female Drosophila. Here we report that mifepristone blocked this effect, yielding life span increases up to +68%. Drug was fed to females after mating, in the absence of males, demonstrating function in females. Mifepristone did not increase life span of virgin females or males. Mifepristone reduced progeny production but did not reduce food intake. High-throughput RNA sequencing was used to identify genes up-regulated or down-regulated upon mating, and where the change was reduced by mifepristone. Five candidate positive regulators of life span were identified, including dosage compensation regulator Unr and three X-linked genes: multi sex combs (PcG gene), Dopamine 2-like receptor and CG14215. The 37 candidate negative genes included neuropeptide CNMamide and several involved in protein mobilization and immune response. The results inform the interpretation of experiments involving mifepristone, and implicate steroid hormone signaling in regulating the trade-off between reproduction and life span. ER -

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Wu Z, Yu Y, Liu C, Xiong Y, Montani J, Yang Z, Ming X, . Role of p38 mitogen-activated protein kinase in vascular endothelial aging: Interaction with Arginase-II and S6K1 signaling pathway. . 7:70-81. https://doi.org/10.18632/aging.100722

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Provider: TY - JOUR AU - Wu, Zongsong AU - Yu, Yi AU - Liu, Chang AU - Xiong, Yuyan AU - Montani, Jean-Pierre AU - Yang, Zhihong AU - Ming, Xiu-Fen TI - Role of p38 mitogen-activated protein kinase in vascular endothelial aging: Interaction with Arginase-II and S6K1 signaling pathway JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100722 DO - 10.18632/aging.100722 SP - 70 EP - 81 PY - ER -

Provider: TY - JOUR AU - Wu, Zongsong AU - Yu, Yi AU - Liu, Chang AU - Xiong, Yuyan AU - Montani, Jean-Pierre AU - Yang, Zhihong AU - Ming, Xiu-Fen TI - Role of p38 mitogen-activated protein kinase in vascular endothelial aging: Interaction with Arginase-II and S6K1 signaling pathway JO - JA - VL - 7 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100722 DO - 10.18632/aging.100722 SP - 70 EP - 81 PY - AB - p38 mitogen-activated protein kinase (p38) regulates cellular senescence and senescence-associated secretory phenotype (SASP), i.e., secretion of cytokines and/or chemokines. Previous work showed that augmented arginase-II (Arg-II) and S6K1 interact with each other to promote endothelial senescence through uncoupling of endothelial nitric oxide synthase (eNOS). Here we demonstrate eNOS-uncoupling, augmented expression/secretion of IL-6 and IL-8, elevation of p38 activation and Arg-II levels in senescent endothelial cells. Silencing Arg-II or p38α in senescent cells recouples eNOS and inhibits IL-6 and IL-8 secretion. Overexpression of Arg-II in young endothelial cells causes eNOS-uncoupling and enhances IL-6 and IL-8 expression/secretion, which is prevented by p38 inhibition or by antioxidant. Moreover, p38 activation and expression of IL-6 and KC (the murine IL-8 homologue) are increased in the heart and/or aortas of wild type (WT) old mice, which is abolished in mice with Arg-II gene deficiency (Arg-II−/−). In addition, inhibition of p38 in the old WT mice recouples eNOS function and reduces IL-6 and KC expression in the aortas and heart. Silencing Arg-II or p38α or S6K1 inhibits each other in senescence endothelial cells. Thus, Arg-II, p38, and S6K1 form a positive circuit which regulates endothelial senescence and cardiovascular aging ER -

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