Volume 5, Issue 1

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Doles J, Keyes WM, . Epidermal stem cells undergo age-associated changes. . 5:1-2. https://doi.org/10.18632/aging.100530

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Provider: TY - JOUR AU - Doles, Jason AU - Keyes, William M. TI - Epidermal stem cells undergo age-associated changes JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100530 DO - 10.18632/aging.100530 SP - 1 EP - 2 PY - ER -

Provider: TY - JOUR AU - Doles, Jason AU - Keyes, William M. TI - Epidermal stem cells undergo age-associated changes JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100530 DO - 10.18632/aging.100530 SP - 1 EP - 2 PY - AB - ER -

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Zhou J, Richardson M, Reddy V, Menon M, Barrack ER, Reddy GP, Kim S, . Structural and functional association of androgen receptor with telomeres in prostate cancer cells. . 5:3-17. https://doi.org/10.18632/aging.100524

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Provider: TY - JOUR AU - Zhou, Junying AU - Richardson, Michelle AU - Reddy, Vidyavathi AU - Menon, Mani AU - Barrack, Evelyn R. AU - Reddy, G. Prem-Veer AU - Kim, Sahn-Ho TI - Structural and functional association of androgen receptor with telomeres in prostate cancer cells JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100524 DO - 10.18632/aging.100524 SP - 3 EP - 17 PY - ER -

Provider: TY - JOUR AU - Zhou, Junying AU - Richardson, Michelle AU - Reddy, Vidyavathi AU - Menon, Mani AU - Barrack, Evelyn R. AU - Reddy, G. Prem-Veer AU - Kim, Sahn-Ho TI - Structural and functional association of androgen receptor with telomeres in prostate cancer cells JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100524 DO - 10.18632/aging.100524 SP - 3 EP - 17 PY - AB - Telomeres protect the ends of linear chromosomes from being recognized as damaged DNA, and telomere stability is required for genome stability. Here we demonstrate that telomere stability in androgen receptor (AR)-positive LNCaP human prostate cancer cells is dependent on AR and androgen, as AR inactivation by AR antagonist bicalutamide (Casodex), AR-knockdown, or androgen-depletion caused telomere dysfunction, and the effect of androgen-depletion or Casodex was blocked by the addition of androgen. Notably, neither actinomycin D nor cycloheximide blocked the DNA damage response to Casodex, indicating that the role of AR in telomere stability is independent of its role in transcription. We also demonstrate that AR is a component of telomeres, as AR-bound chromatin contains telomeric DNA, and telomeric chromatin contains AR. Importantly, AR inactivation by Casodex caused telomere aberrations, including multiple abnormal telomere signals, remindful of a fragile telomere phenotype that has been described previously to result from defective telomere DNA replication. We suggest that AR plays an important role in telomere stability and replication of telomere DNA in prostate cancer cells, and that AR inactivation-mediated telomere dysfunction may contribute to genomic instability and progression of prostate cancer cells. ER -

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Bektas A, Zhang Y, Wood WH, Becker KG, Madara K, Ferrucci L, Sen R, . Age-associated alterations in inducible gene transcription in human CD4⁺ T lymphocytes. . 5:18-36. https://doi.org/10.18632/aging.100522

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Provider: TY - JOUR AU - Bektas, Arsun AU - Zhang, Yongqing AU - Wood, William H. AU - Becker, Kevin G. AU - Madara, Karen AU - Ferrucci, Luigi AU - Sen, Ranjan TI - Age-associated alterations in inducible gene transcription in human CD4⁺ T lymphocytes JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100522 DO - 10.18632/aging.100522 SP - 18 EP - 36 PY - ER -

Provider: TY - JOUR AU - Bektas, Arsun AU - Zhang, Yongqing AU - Wood, William H. AU - Becker, Kevin G. AU - Madara, Karen AU - Ferrucci, Luigi AU - Sen, Ranjan TI - Age-associated alterations in inducible gene transcription in human CD4⁺ T lymphocytes JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100522 DO - 10.18632/aging.100522 SP - 18 EP - 36 PY - AB - Age associated immune dysregulation results in a pro-inflammatory state and increased susceptibility to infections and autoimmune diseases. Studies show that signaling initiated at the T cell antigen receptor (TCR) is impaired in CD4+ T cells from old compared to young mice. Here we examined TCR-inducible gene expression changes in CD4+ T cells during human aging. We reveal a dichotomy in gene expression mediated by the inducible transcription factor NF-κB. Most NF-κB target genes are not induced in a sustained manner in cells derived from older compared to younger individuals. However, a subset of NF-κB target genes including genes associated with chronic pro-inflammatory state in the elderly, such as interleukin 1 and 6, continue to be up-regulated even in the absence of NF-κB induction. In addition, we identify other widespread changes in gene expression between cells derived from older and younger individuals. Surprisingly, many of the most noteworthy age-associated changes in human CD4+ T cells differ from those seen in murine models. Our studies provide the first view of age-associated alteration of TCR-inducible gene expression in human CD4+ T cells. ER -

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Georgakopoulou E, Tsimaratou K, Evangelou K, Fernandez M, Zoumpourlis V, Trougakos I, Kletsas D, Bartek J, Serrano M, Gorgoulis V, . Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues. . 5:37-50. https://doi.org/10.18632/aging.100527

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Provider: TY - JOUR AU - Georgakopoulou, EA AU - Tsimaratou, K AU - Evangelou, K AU - Fernandez, Marcos-PJ AU - Zoumpourlis, V AU - Trougakos, IP AU - Kletsas, D AU - Bartek, J AU - Serrano, M AU - Gorgoulis, VG TI - Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100527 DO - 10.18632/aging.100527 SP - 37 EP - 50 PY - ER -

Provider: TY - JOUR AU - Georgakopoulou, EA AU - Tsimaratou, K AU - Evangelou, K AU - Fernandez, Marcos-PJ AU - Zoumpourlis, V AU - Trougakos, IP AU - Kletsas, D AU - Bartek, J AU - Serrano, M AU - Gorgoulis, VG TI - Specific lipofuscin staining as a novel biomarker to detect replicative and stress-induced senescence. A method applicable in cryo-preserved and archival tissues JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100527 DO - 10.18632/aging.100527 SP - 37 EP - 50 PY - AB - There is shortage of extensive clinicopathologic studies of cellular senescence because the most reliable senescence biomarker, the detection of Senescence-Associated-beta-galactosidase activity (SA-β-gal), is inapplicable in archival material and requires snap-frozen tissues. We validated the histochemical Sudan-Black-B (SBB) specific stain of lipofuscin, an aggregate of oxidized proteins, lipids and metals, known to accumulate in aged tissues, as an additional reliable approach to detect senescent cells independently of sample preparation. We analyzed cellular systems in which senescence was triggered by replicative exhaustion or stressful stimuli, conditional knock-in mice producing precancerous lesions exhibiting senescence, and human preneoplastic lesions known to contain senescent cells. In the above settings we demonstrated co-localization of lipofuscin and SA-β-gal in senescent cells in vitro and in vivo (cryo-preserved tissue), strongly supporting the candidacy of lipofuscin for a biomarker of cellular senescence. Furthermore, cryo-preserved tissues positive for SA-β-gal were formalin-fixed, paraffin-embedded, and stained with SBB. The corresponding SA-β-gal positive tissue areas stained specifically for lipofuscin by SBB, whereas tissues negative for SA-β-gal were lipofuscin negative, validating the sensitivity and specificity of the SBB staining to visualize senescent cells in archival material. The latter unique property of SBB could be exploited in research on widely available retrospective tissue material. ER -

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Rabin DM, Rabin RL, Blenkinsop TA, Temple S, Stern JH, . Chronic oxidative stress upregulates Drusen-related protein expression in adult human RPE stem cell-derived RPE cells: A novel culture model for dry AMD. . 5:51-66. https://doi.org/10.18632/aging.100516

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Provider: TY - JOUR AU - Rabin, David M. AU - Rabin, Richard L. AU - Blenkinsop, Timothy A. AU - Temple, Sally AU - Stern, Jeffrey H. TI - Chronic oxidative stress upregulates Drusen-related protein expression in adult human RPE stem cell-derived RPE cells: A novel culture model for dry AMD JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100516 DO - 10.18632/aging.100516 SP - 51 EP - 66 PY - ER -

Provider: TY - JOUR AU - Rabin, David M. AU - Rabin, Richard L. AU - Blenkinsop, Timothy A. AU - Temple, Sally AU - Stern, Jeffrey H. TI - Chronic oxidative stress upregulates Drusen-related protein expression in adult human RPE stem cell-derived RPE cells: A novel culture model for dry AMD JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100516 DO - 10.18632/aging.100516 SP - 51 EP - 66 PY - AB - Purpose The goal of this study was to examine changes in the expression of transcripts and proteins associated with drusen in Age-related Macular Degeneration (AMD) after exposing human retinal pigment epithelium (hRPE) cells to chronic oxidative stress. Methods Primary adult human RPE cells were isolated from cadaveric donor eyes. The subpopulation of RPE stem cells (RPESCs) was activated, expanded, and then differentiated into RPE progeny. Confluent cultures of RPESC-derived hRPE and ARPE-19 cells were exposed to a regimen of tert-butylhydroperoxide (TBHP) for 1-5 days. After treatment, gene expression was measured by quantitative PCR (qPCR), protein expression was assessed by immunocytochemistry and transepithelial resistance and cell toxicity were measured. Results hRPE cells exposed to a regimen of TBHP for 5 days upregulate expression of several molecules identified in drusen, including molecular chaperones and pro-angiogenic factors. 5-day TBHP treatment was significantly more effective than 1-day treatment at eliciting these effects. The extent of hRPE response to 5-day treatment varied significantly between individual donors, nevertheless, 6 transcripts were reliably significantly upregulated. ARPE-19 cells treated with the same 5-day stress regime did not show the same pattern of response and did not upregulate this group of transcripts. Conclusions RPESC-derived hRPE cells change significantly when exposed to repeated oxidative stress conditions, upregulating expression of several drusen-related proteins and transcripts. This is consistent with the hypothesis that hRPE cells are competent to be a source of proteins found in drusen deposits. Our results suggest that donor-specific genetic and environmental factors influence the RPE stress response. ARPE-19 cells appear to be less representative of AMD-like changes than RPESC-derived hRPE. This adult stem cell-based system using chronic TBHP treatment of hRPE represents a novel in vitro model useful for the study of drusen formation and dry AMD pathophysiology. ER -

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Kawałek A, Lefevre SD, Veenhuis M, van der Klei IJ, . Peroxisomal catalase deficiency modulates yeast lifespan depending on growth conditions. . 5:67-83. https://doi.org/10.18632/aging.100519

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Provider: TY - JOUR AU - Kawałek, Adam AU - Lefevre, Sophie D. AU - Veenhuis, Marten AU - van der Klei, Ida J. TI - Peroxisomal catalase deficiency modulates yeast lifespan depending on growth conditions JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100519 DO - 10.18632/aging.100519 SP - 67 EP - 83 PY - ER -

Provider: TY - JOUR AU - Kawałek, Adam AU - Lefevre, Sophie D. AU - Veenhuis, Marten AU - van der Klei, Ida J. TI - Peroxisomal catalase deficiency modulates yeast lifespan depending on growth conditions JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100519 DO - 10.18632/aging.100519 SP - 67 EP - 83 PY - AB - We studied the role of peroxisomal catalase in chronological aging of the yeastHansenula polymorpha in relation to various growth substrates. Catalase-deficient (cat) cells showed a similar chronological life span (CLS) relative to the wild-type control upon growth on carbon and nitrogen sources that are not oxidized by peroxisomal enzymes. However, when media contained methylamine, which is oxidized by peroxisomal amine oxidase, the CLS of cat cells was significantly reduced. Conversely, the CLS of cat cells was enhanced relative to the wild-type control, when cells were grown on methanol, which is oxidized by peroxisomal alcohol oxidase. At these conditions strongly enhanced ROS levels were observed during the exponential growth phase of cat cells. This was paralleled by activation of the transcription factor Yap1, as well as an increase in the levels of the antioxidant enzymes cytochrome c peroxidase and superoxide dismutase. Upon deletion of the genes encoding Yap1 or cytochrome c peroxidase, the CLS extension of cat cells on methanol was abolished. These findings reveal for the first time an important role of enhanced cytochrome c peroxidase levels in yeast CLS extension. ER -

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Howcroft TK, Campisi J, Louis GB, Smith MT, Wise B, Wyss-Coray T, Augustine AD, McElhaney JE, Kohanski R, Sierra F, . The role of inflammation in age-related disease. . 5:84-93. https://doi.org/10.18632/aging.100531

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Provider: TY - JOUR AU - Howcroft, T. Kevin AU - Campisi, Judith AU - Louis, Germaine Buck AU - Smith, Martyn T. AU - Wise, Bradley AU - Wyss-Coray, Tony AU - Augustine, Alison Deckhut AU - McElhaney, Janet E. AU - Kohanski, Ron AU - Sierra, Felipe TI - The role of inflammation in age-related disease JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100531 DO - 10.18632/aging.100531 SP - 84 EP - 93 PY - ER -

Provider: TY - JOUR AU - Howcroft, T. Kevin AU - Campisi, Judith AU - Louis, Germaine Buck AU - Smith, Martyn T. AU - Wise, Bradley AU - Wyss-Coray, Tony AU - Augustine, Alison Deckhut AU - McElhaney, Janet E. AU - Kohanski, Ron AU - Sierra, Felipe TI - The role of inflammation in age-related disease JO - JA - VL - 5 IS - 1 PB - SN - UR - https://doi.org/10.18632/aging.100531 DO - 10.18632/aging.100531 SP - 84 EP - 93 PY - AB - The National Institutes of Health (NIH) Geroscience Interest Group (GSIG) sponsored workshop, The Role of Inflammation in Age-Related Disease, was held September 6th-7th, 2012 in Bethesda, MD. It is now recognized that a mild pro-inflammatory state is correlated with the major degenerative diseases of the elderly. The focus of the workshop was to better understand the origins and consequences of this low level chronic inflammation in order to design appropriate interventional studies aimed at improving healthspan. Four sessions explored the intrinsic, environmental exposures and immune pathways by which chronic inflammation are generated, sustained, and lead to age-associated diseases. At the conclusion of the workshop recommendations to accelerate progress toward understanding the mechanistic bases of chronic disease were identified. ER -

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