Volume 4, Issue 7

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Caiafa P, Zampieri M, . Why is DNA methylation of Igf2 CpG island shore affected during ageing?. . 4:448-449. https://doi.org/10.18632/aging.100473

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Provider: TY - JOUR AU - Caiafa, Paola AU - Zampieri, Michele TI - Why is DNA methylation of <i>Igf2 CpG</i> island shore affected during ageing? JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100473 DO - 10.18632/aging.100473 SP - 448 EP - 449 PY - ER -

Provider: TY - JOUR AU - Caiafa, Paola AU - Zampieri, Michele TI - Why is DNA methylation of <i>Igf2 CpG</i> island shore affected during ageing? JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100473 DO - 10.18632/aging.100473 SP - 448 EP - 449 PY - AB - ER -

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Blagosklonny MV, . Tumor suppression by p53 without apoptosis and senescence: conundrum or rapalog-like gerosuppression?. . 4:450-455. https://doi.org/10.18632/aging.100475

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Provider: TY - JOUR AU - Blagosklonny, Mikhail V. TI - Tumor suppression by p53 without apoptosis and senescence: conundrum or rapalog-like gerosuppression? JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100475 DO - 10.18632/aging.100475 SP - 450 EP - 455 PY - ER -

Provider: TY - JOUR AU - Blagosklonny, Mikhail V. TI - Tumor suppression by p53 without apoptosis and senescence: conundrum or rapalog-like gerosuppression? JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100475 DO - 10.18632/aging.100475 SP - 450 EP - 455 PY - AB - I discuss a very obscure activity of p53, namely suppression of senescence (gerosuppression), which is also manifested as anti-hypertrophic, anti-hypermetabolic, anti-inflammatory and anti-secretory effects of p53. But can gerossuppression suppress tumors? ER -

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Pardo PS, Boriek AM, . An autoregulatory loop reverts the mechanosensitive Sirt1 induction by EGR1 in skeletal muscle cells. . 4:456-461. https://doi.org/10.18632/aging.100470

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Provider: TY - JOUR AU - Pardo, Patricia S. AU - Boriek, Aladin M. TI - An autoregulatory loop reverts the mechanosensitive <i>Sirt1</i> induction by EGR1 in skeletal muscle cells JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100470 DO - 10.18632/aging.100470 SP - 456 EP - 461 PY - ER -

Provider: TY - JOUR AU - Pardo, Patricia S. AU - Boriek, Aladin M. TI - An autoregulatory loop reverts the mechanosensitive <i>Sirt1</i> induction by EGR1 in skeletal muscle cells JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100470 DO - 10.18632/aging.100470 SP - 456 EP - 461 PY - AB - Muscle contraction is associated with the production of reactive oxygen species (ROS). Mechanisms of ROS scavenging are fundamental to avoid muscle damage. We had previously discovered a stretch-induced genetic program in myotubes that triggers an antioxidant defense. At the core of this mechanism, transcriptional activation of SIRT1 by the early growth response protein EGR1 results in increased MnSOD activity through the activation of Sod2 by SIRT1/FOXO pathway. In this report, we show experimental evidence that; a) EGR1 and SIRT1 proteins physically interact at the time of maximal Sirt1 induction, b) SIRT1 has a negative effect on the activation of the Sirt1 promoter by EGR1. Thus, the interaction between EGR1 and SIRT1 describes an autoregulatory loop that shuts down the stretch-induced Sirt1 expression. ER -

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Calnan DR, Webb AE, White JL, Stowe TR, Goswami T, Shi X, Espejo A, Bedford MT, Gozani O, Gygi SP, Brunet A, . Methylation by Set9 modulates FoxO3 stability and transcriptional activity. . 4:462-479. https://doi.org/10.18632/aging.100471

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Provider: TY - JOUR AU - Calnan, Daniel R. AU - Webb, Ashley E. AU - White, Jamie L. AU - Stowe, Timothy R. AU - Goswami, Tapasree AU - Shi, Xiaobing AU - Espejo, Alexsandra AU - Bedford, Mark T. AU - Gozani, Or AU - Gygi, Steven P. AU - Brunet, Anne TI - Methylation by Set9 modulates FoxO3 stability and transcriptional activity JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100471 DO - 10.18632/aging.100471 SP - 462 EP - 479 PY - ER -

Provider: TY - JOUR AU - Calnan, Daniel R. AU - Webb, Ashley E. AU - White, Jamie L. AU - Stowe, Timothy R. AU - Goswami, Tapasree AU - Shi, Xiaobing AU - Espejo, Alexsandra AU - Bedford, Mark T. AU - Gozani, Or AU - Gygi, Steven P. AU - Brunet, Anne TI - Methylation by Set9 modulates FoxO3 stability and transcriptional activity JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100471 DO - 10.18632/aging.100471 SP - 462 EP - 479 PY - AB - The FoxO family of transcription factors plays an important role in longevity and tumor suppression by regulating the expression of a wide range of target genes. FoxO3 has recently been found to be associated with extreme longevity in humans and to regulate the homeostasis of adult stem cell pools in mammals, which may contribute to longevity. The activity of FoxO3 is controlled by a variety of post-translational modifications that have been proposed to form a ‘code’ affecting FoxO3 subcellular localization, DNA binding ability, protein-protein interactions and protein stability. Lysine methylation is a crucial post-translational modification on histones that regulates chromatin accessibility and is a key part of the ‘histone code’. However, whether lysine methylation plays a role in modulating FoxO3 activity has never been examined. Here we show that the methyltransferase Set9 directly methylates FoxO3 in vitro and in cells. Using a combination of tandem mass spectrometry and methyl-specific antibodies, we find that Set9 methylates FoxO3 at a single residue, lysine 271, a site previously known to be deacetylated by Sirt1. Methylation of FoxO3 by Set9 decreases FoxO3 protein stability, while moderately increasing FoxO3 transcriptional activity. The modulation of FoxO3 stability and activity by methylation may be critical for fine-tuning cellular responses to stress stimuli, which may in turn affect FoxO3's ability to promote tumor suppression and longevity. ER -

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Corominas-Faja B, Quirantes-Piné R, Oliveras-Ferraros C, Vazquez-Martin A, Cufí S, Martin-Castillo B, Micol V, Joven J, Segura-Carretero A, Menendez JA, . Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs. . 4:480-498. https://doi.org/10.18632/aging.100472

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Provider: TY - JOUR AU - Corominas-Faja, Bruna AU - Quirantes-Piné, Rosa AU - Oliveras-Ferraros, Cristina AU - Vazquez-Martin, Alejandro AU - Cufí, Sílvia AU - Martin-Castillo, Begoña AU - Micol, Vicente AU - Joven, Jorge AU - Segura-Carretero, Antonio AU - Menendez, Javier A. TI - Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100472 DO - 10.18632/aging.100472 SP - 480 EP - 498 PY - ER -

Provider: TY - JOUR AU - Corominas-Faja, Bruna AU - Quirantes-Piné, Rosa AU - Oliveras-Ferraros, Cristina AU - Vazquez-Martin, Alejandro AU - Cufí, Sílvia AU - Martin-Castillo, Begoña AU - Micol, Vicente AU - Joven, Jorge AU - Segura-Carretero, Antonio AU - Menendez, Javier A. TI - Metabolomic fingerprint reveals that metformin impairs one-carbon metabolism in a manner similar to the antifolate class of chemotherapy drugs JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100472 DO - 10.18632/aging.100472 SP - 480 EP - 498 PY - AB - Metabolomic fingerprint of breast cancer cells treated with the antidiabetic drug metformin revealed a significant accumulation of 5-formimino-tetrahydrofolate, one of the tetrahydrofolate forms carrying activated one-carbon units that are essential for the de novo synthesis of purines and pyrimidines. De novo synthesis of glutathione, a folate-dependent pathway interconnected with one-carbon metabolism was concomitantly depleted in response to metformin. End-product reversal studies demonstrated that thymidine alone leads to a significant but incomplete protection from metformin's cytostatic effects. The addition of the substrate hypoxanthine for the purine salvage pathway produces major rightward shifts in metformin's growth inhibition curves. Metformin treatment failed to activate the DNA repair protein ATM kinase and the metabolic tumor suppressor AMPK when thymidine and hypoxanthine were present in the extracellular milieu. Our current findings suggest for the first time that metformin can function as an antifolate chemotherapeutic agent that induces the ATM/AMPK tumor suppressor axis secondarily following the alteration of the carbon flow through the folate-related one-carbon metabolic pathways. ER -

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Rascón B, Hubbard BP, Sinclair DA, Amdam GV, . The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction. . 4:499-508. https://doi.org/10.18632/aging.100474

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Provider: TY - JOUR AU - Rascón, Brenda AU - Hubbard, Basil P. AU - Sinclair, David A. AU - Amdam, Gro V. TI - The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100474 DO - 10.18632/aging.100474 SP - 499 EP - 508 PY - ER -

Provider: TY - JOUR AU - Rascón, Brenda AU - Hubbard, Basil P. AU - Sinclair, David A. AU - Amdam, Gro V. TI - The lifespan extension effects of resveratrol are conserved in the honey bee and may be driven by a mechanism related to caloric restriction JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100474 DO - 10.18632/aging.100474 SP - 499 EP - 508 PY - AB - Our interest in healthy aging and in evolutionarily conserved mechanisms of lifespan extension prompted us to investigate whether features of age-related decline in the honey bee could be attenuated with resveratrol. Resveratrol is regarded as a caloric restriction mimetic known to extend lifespan in some but not all model species. The current, prevailing view is that resveratrol works largely by activating signaling pathways. It has also been suggested that resveratrol may act as an antioxidant and confer protection against nervous system impairment and oxidative stress. To test whether honey bee lifespan, learning performance, and food perception could be altered by resveratrol, we supplemented the diets of honey bees and measured lifespan, olfactory learning, and gustatory responsiveness to sucrose. Furthermore, to test the effects of resveratrol under metabolic challenge, we used hyperoxic environments to generate oxidative stress. Under normal oxygen conditions, two resveratrol treatments—30 and 130 μM—lengthened average lifespan in wild-type honey bees by 38% and 33%, respectively. Both resveratrol treatments also lengthened maximum and median lifespan. In contrast, hyperoxic stress abolished the resveratrol life-extension response. Furthermore, resveratrol did not affect learning performance, but did alter gustation. Honey bees that were not fed resveratrol exhibited greater responsiveness to sugar, while those supplemented with resveratrol were less responsive to sugar. We also discovered that individuals fed a high dose of resveratrol—compared to controls—ingested fewer quantities of food under ad libitum feeding conditions. ER -

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Pirazzini C, Giuliani C, Bacalini MG, Boattini A, Capri M, Fontanesi E, Marasco E, Mantovani V, Pierini M, Pini E, Luiselli D, Franceschi C, Garagnani P, . Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age. . 4:509-520. https://doi.org/10.18632/aging.100476

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Provider: TY - JOUR AU - Pirazzini, Chiara AU - Giuliani, Cristina AU - Bacalini, Maria Giulia AU - Boattini, Alessio AU - Capri, Miriam AU - Fontanesi, Elisa AU - Marasco, Elena AU - Mantovani, Vilma AU - Pierini, Michela AU - Pini, Elisa AU - Luiselli, Donata AU - Franceschi, Claudio AU - Garagnani, Paolo TI - Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100476 DO - 10.18632/aging.100476 SP - 509 EP - 520 PY - ER -

Provider: TY - JOUR AU - Pirazzini, Chiara AU - Giuliani, Cristina AU - Bacalini, Maria Giulia AU - Boattini, Alessio AU - Capri, Miriam AU - Fontanesi, Elisa AU - Marasco, Elena AU - Mantovani, Vilma AU - Pierini, Michela AU - Pini, Elisa AU - Luiselli, Donata AU - Franceschi, Claudio AU - Garagnani, Paolo TI - Space/Population and Time/Age in DNA methylation variability in humans: a study on IGF2/H19 locus in different Italian populations and in mono- and di-zygotic twins of different age JO - JA - VL - 4 IS - 7 PB - SN - UR - https://doi.org/10.18632/aging.100476 DO - 10.18632/aging.100476 SP - 509 EP - 520 PY - AB - Little is known about the impact of space (geography/ancestry) and time (age of the individuals) on DNA methylation variability in humans. We investigated DNA methylation of the imprinted IGF2/H19 locus in: i) a cohort of individuals homogeneous for age and gender (males with restricted age range: 30-50 years) belonging to four Italian districts representative of the major genetic clines, informative for the geographical dimension; ii) a cohort of monozygotic (MZ) and dizygotic (DZ) twins of different ages (age-range: 22-97 years), informative for the temporal dimension. DNA methylation of the analyzed regions displayed high levels of inter-individual variability that could not be ascribed to any geographical cline. In MZ twins we identified two IGF2/H19 regions where the intra-couple variations significantly increased after the age of 60 years. The analysis of twins’ individual life histories suggests that the within twin pairs difference is likely the result of the aging process itself, as sharing a common environment for long periods had no effect on DNA methylation divergence. On the whole, the data here reported suggest that: i) aging more than population genetics is responsible for the inter-individual variability in DNA methylation patterns in humans; ii) DNA methylation variability appears to be highly region-specific. ER -

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