المؤلفون: Matteo Perillo, Alessia Silla, Angela Punzo, Cristiana Caliceti, Andres Kriete, Christian Sell, Antonello Lorenzini

المصدر: Biomedical Journal, Vol 47, Iss 2, Pp 100654- (2024)

مصطلحات موضوعية: Peto's paradox, Longevity, Body mass, Hallmarks of cancer, Evolution, Mini-review, Medicine (General), R5-920, Biology (General), QH301-705.5

الوصف: Comparative oncology is an understudied field of science. We are far from understanding the key mechanisms behind Peto's paradox, i.e., understanding how long-lived and large animals are not subject to a higher cancer burden despite the longer exposure time to mutations and the larger number of cells exposed.In this work, we investigated the scientific evidence on such mechanisms through a systematic mini-review of the literature about the relation of longevity and/or large body mass with physiological, genetic, or environmental traits among mammalian species. More than forty thousand articles were retrieved from three repositories, and 383 of them were screened using an active-learning-based tool. Of those, 36 articles on longevity and 37 on body mass were selected for the review. Such articles were examined focusing on: number and type of species considered, statistical methods used, traits investigated, and observed relationship with longevity and/or body mass. Where applicable, the traits investigated were matched with one or more hallmarks of cancer.We obtained a list of potential candidate traits to explain Peto's paradox related to replicative immortality, cell senescence, genome instability and mutations, proliferative signaling, growth suppression evasion, and cell resistance to death.Our investigation suggests that different strategies have been followed to prevent cancer in large and long-lived species. The large number of papers retrieved emphasizes that more studies can be launched in the future, using more efficient analytical approaches to comprehensively evaluate the convergent biological mechanisms essential for acquiring longevity and large body mass without increasing cancer risk.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2319417023000914Test; https://doaj.org/toc/2319-4170Test

الوصول الحر: https://doaj.org/article/52b563343683439e927f704770ab2ed5Test

المؤلفون: Matteo Perillo, Angela Punzo, Cristiana Caliceti, Christian Sell, Antonello Lorenzini

المصدر: Biomedical Journal, Vol 46, Iss 3, Pp 100596- (2023)

مصطلحات موضوعية: Cell culture immortalization, Replicative senescence, Longevity, Body mass, Partial correlation, Phylogenetic regression, Medicine (General), R5-920, Biology (General), QH301-705.5

الوصف: Background: The Peto's paradox consists in the observation that individuals from long-lived and large animal species do not experience a higher cancer incidence, despite being exposed for longer time to the possibility of accumulating mutations and having more target cells exposed to the phenomenon. The existence of this paradox has been recently confirmed (Vincze et al., 2022). Concurrently, robust evidence has been published that longevity involves a convergent evolution of cellular mechanisms that prevent the accumulation of mutations (Cagan et al., 2022). It remains unclear which cellular mechanisms are critical to allow the evolution of a large body mass while keeping cancer at bay. Methods: Adding to existing data linking cellular replicative potential and species body mass (Lorenzini et al., 2005), we have grown a total of 84 skin fibroblast cell strains from 40 donors of 17 mammalian species and analyzed their Hayflick's limit, i.e., their senescent plateau, and eventual spontaneous immortalization escape. The correlation of immortalization and replicative capacity of the species with their longevity, body mass and metabolism has been assessed through phylogenetic multiple linear regression (MLR). Results: The immortalization probability is negatively related to species body mass. The new evaluation and additional data about replicative potential strengthen our previous observation, confirming that stable and extended proliferation is strongly correlated with the evolution of a large body mass rather than lifespan. Conclusion: The relation between immortalization and body mass suggests a need to evolve stringent mechanisms that control genetic stability during the evolution of a large body mass.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2319417023000331Test; https://doaj.org/toc/2319-4170Test

الوصول الحر: https://doaj.org/article/c89a748e0af3451b805400fd86bb2b51Test

المؤلفون: Larissa Vierl, Charlotte Von Bremen, York Hagmayer, Cord Benecke, Christian Sell

المصدر: Frontiers in Psychology, Vol 14 (2023)

مصطلحات موضوعية: network analysis, Operationalized Psychodynamic Diagnosis (OPD-2), personality functioning, level of structural integration, conflicts, Psychology, BF1-990

الوصف: Personality functioning and psychodynamic conflicts are central constructs in psychoanalytic theories of psychopathology as well as in many psychodynamic treatment models. Although there has been a longstanding conceptual discussion on how they relate to each other, empirical evidence on this question is still scarce. In this study, we explore the associations between psychodynamic conflicts and levels of structural integration (which can be used synonymously with personality functioning) by means of a partial correlation network analysis in a sample of N = 220 outpatients interviewed and rated according to Operationalized Psychodynamic Diagnosis (OPD-2). We examined network centrality, bridge centrality, clustering, and network stability. The network analysis resulted in separate clusters for levels of structural integration and conflicts, supporting the assumption of distinct psychodynamic constructs. The greatest association between the two clusters was found between the individuation vs. dependency conflict (C1) and the structural capacity to attach to internal objects. In general, C1 showed significantly greater connections with structural dimensions compared to the other five OPD conflicts included. C1 was also more central in the network compared to most other conflicts, whereas the structural dimensions did not differ in centrality. All structural dimensions were found to be strongly interconnected. C1 showed exclusively negative edges to the other conflicts, suggesting that a profound C1 decreases the probability of other psychodynamic conflicts. We discuss clinical as well as conceptual implications of our findings for psychodynamic diagnosis and treatment.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fpsyg.2023.1152150/fullTest; https://doaj.org/toc/1664-1078Test

الوصول الحر: https://doaj.org/article/bf004b29fcac4deb8cdcc5a9c4731445Test

المؤلفون: Jule Bauckhage, Christian Sell

المصدر: Research in Psychotherapy, Vol 24, Iss 3 (2021)

مصطلحات موضوعية: Guided affective imagery, guided imagery psychotherapy, differential indication, psychodynamic therapy, tacit knowledge., Psychology, BF1-990

الوصف: Guided imagery psychotherapy (GIP) is an established therapeutic method using creative mental imagery within a psychodynamic frame of reference. Although there is evidence for the method’s general effectiveness, it is yet unclear under which conditions and for which patients it should be used. The aim of this study was therefore to empirically identify indication criteria for the use of guided affective imagery (GAI) as part of psychodynamic therapies. We conducted semi-structured interviews with N=15 psychodynamic therapists also qualified as GAI training therapists. We asked them to recollect cases in which they had decided either for or against the use of imagery. The therapists described a complex interplay of different factors. Using grounded theory coding supplemented by elements of Consensual Qualitative Research we reconstructed from their accounts a sequential model of their indicative decisions. First, there is a consideration of clear contraindications related to reality testing and destructiveness. Second, there are aspects requiring a modified application of GAI such as emotional instability and post-traumatic stress disorder symptoms. In a final step, there are a number of characteristics of the patient, the therapist, the therapeutic relationship, the patients’ initial imagery and different therapeutic goals and foci which are weighed relatively to each other in order for therapists to reach an indication decision. We end by discussing ways in which the indicative decision model may be used to improve GAI training as well as the method’s differential efficacy and effectiveness.

وصف الملف: electronic resource

العلاقة: https://www.researchinpsychotherapy.org/index.php/rpsy/article/view/577Test; https://doaj.org/toc/2499-7552Test; https://doaj.org/toc/2239-8031Test

الوصول الحر: https://doaj.org/article/57b942df365f44caabe317071412a479Test

المؤلفون: Martina Unterländer, Friso Palstra, Iosif Lazaridis, Aleksandr Pilipenko, Zuzana Hofmanová, Melanie Groß, Christian Sell, Jens Blöcher, Karola Kirsanow, Nadin Rohland, Benjamin Rieger, Elke Kaiser, Wolfram Schier, Dimitri Pozdniakov, Aleksandr Khokhlov, Myriam Georges, Sandra Wilde, Adam Powell, Evelyne Heyer, Mathias Currat, David Reich, Zainolla Samashev, Hermann Parzinger, Vyacheslav I. Molodin, Joachim Burger

المصدر: Nature Communications, Vol 8, Iss 1, Pp 1-10 (2017)

مصطلحات موضوعية: Science

الوصف: The Scythian culture was widespread throughout the Eurasian Steppe during the 1stmillennium BCE. This study provides genetic evidence for two independent origins for the Scythians in the eastern and western steppe with varying proportions of Yamnaya and East Asian ancestry, and gene flow among them.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/94fc29ade0014d1880781a3baf7f5583Test

المؤلفون: Valentina Salvestrini, Christian Sell, Antonello Lorenzini

المصدر: Frontiers in Endocrinology, Vol 10 (2019)

مصطلحات موضوعية: obesity, overweight, aging, aging hallmarks, caloric restriction, Diseases of the endocrine glands. Clinical endocrinology, RC648-665

الوصف: Lines of evidence from several studies have shown that increases in life expectancy are now accompanied by increased disability rate. The expanded lifespan of the aging population imposes a challenge on the continuous increase of chronic disease. The prevalence of overweight and obesity is increasing at an alarming rate in many parts of the world. Further to increasing the onset of metabolic imbalances, obesity leads to reduced life span and affects cellular and molecular processes in a fashion resembling aging. Nine key hallmarks of the aging process have been proposed. In this review, we will review these hallmarks and discuss pathophysiological changes that occur with obesity, that are similar to or contribute to those that occur during aging. We present and discuss the idea that obesity, in addition to having disease-specific effects, may accelerate the rate of aging affecting all aspects of physiology and thus shortening life span and health span.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/article/10.3389/fendo.2019.00266/fullTest; https://doaj.org/toc/1664-2392Test

الوصول الحر: https://doaj.org/article/242646cafdc549c9a78d63155589554aTest

المؤلفون: Elizabeth P. Crowe, Ferit Tuzer, Brian D. Gregory, Greg Donahue, Sager J. Gosai, Justin Cohen, Yuk Yee Leung, Emre Yetkin, Raffaella Nativio, Li-San Wang, Christian Sell, Nancy M. Bonini, Shelley L. Berger, F Brad Johnson, Claudio Torres

المصدر: Frontiers in Aging Neuroscience, Vol 8 (2016)

مصطلحات موضوعية: Brain aging, RNA sequencing, Brain oxidative stress, Astrocyte senescence, Astrocyte function, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Aging is a major risk factor for many neurodegenerative disorders. A key feature of aging biology that may underlie these diseases is cellular senescence. Senescent cells accumulate in tissues with age, undergo widespread changes in gene expression, and typically demonstrate altered, pro-inflammatory profiles. Astrocyte senescence has been implicated in neurodegenerative disease, and to better understand senescence-associated changes in astrocytes, we investigated changes in their transcriptome using RNA sequencing. Senescence was induced in human fetal astrocytes by transient oxidative stress. Brain-expressed genes, including those involved in neuronal development and differentiation, were downregulated in senescent astrocytes. Remarkably, several genes indicative of astrocytic responses to injury were also downregulated, including GFAP and genes involved in the processing and presentation of antigens by major histocompatibility complex class II proteins, while pro-inflammatory genes were upregulated. Overall, our findings suggest that senescence-related changes in the function of astrocytes may impact the pathogenesis of age-related brain disorders.

وصف الملف: electronic resource

العلاقة: http://journal.frontiersin.org/Journal/10.3389/fnagi.2016.00208/fullTest; https://doaj.org/toc/1663-4365Test

الوصول الحر: https://doaj.org/article/3ae31c0b3bc84fef8025ad4be73ee323Test

المؤلفون: Ashley Azar, Kathryn Devlin, Joshua Chang Mell, Tania Giovannetti, Vanessa Pirrone, Michael R Nonnemacher, Shendra Passic, Katherine Kercher, Jean W Williams, Jeffery M Jacobson, Brian Wigdahl, William Dampier, David J Libon, Christian Sell

المصدر: PLoS ONE, Vol 11, Iss 10, p e0163772 (2016)

مصطلحات موضوعية: Medicine, Science

الوصف: Evolutionary divergence of the mitochondrial genome has given rise to distinct haplogroups. These haplogroups have arisen in specific geographical locations and are responsible for subtle functional changes in the mitochondria that may provide an evolutionary advantage in a given environment. Based on these functional differences, haplogroups could define disease susceptibility in chronic settings. In this study, we undertook a detailed neuropsychological analysis of a cohort of long-term HIV-1-infected individuals in conjunction with sequencing of their mitochondrial genomes. Stepwise regression analysis showed that the best model for predicting both working memory and declarative memory were age and years since diagnosis. In contrast, years since diagnosis and sub-haplogroup were significantly predictive of psychomotor speed. Consistent with this, patients with haplogroup L3e obtained better scores on psychomotor speed and dexterity tasks when compared to the remainder of the cohort, suggesting that this haplogroup provides a protective advantage when faced with the combined stress of HIV-1 infection and long-term antiretroviral therapies. Differential performance on declarative memory tasks was noted for individuals with other sub-L haplogroups, but these differences were not as robust as the association between L3e and psychomotor speed and dexterity tasks. This work provides evidence that mitochondrial haplogroup is related to neuropsychological test performance among patients in chronic disease settings such as HIV-1 infection.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC5053473?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/63cdb8658ef24f08bdf70dc6849a4ed0Test

المؤلفون: Rekha Bhat, Elizabeth P Crowe, Alessandro Bitto, Michelle Moh, Christos D Katsetos, Fernando U Garcia, Frederick Bradley Johnson, John Q Trojanowski, Christian Sell, Claudio Torres

المصدر: PLoS ONE, Vol 7, Iss 9, p e45069 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Aging is the main risk factor for Alzheimer's disease (AD); however, the aspects of the aging process that predispose the brain to the development of AD are largely unknown. Astrocytes perform a myriad of functions in the central nervous system to maintain homeostasis and support neuronal function. In vitro, human astrocytes are highly sensitive to oxidative stress and trigger a senescence program when faced with multiple types of stress. In order to determine whether senescent astrocytes appear in vivo, brain tissue from aged individuals and patients with AD was examined for the presence of senescent astrocytes using p16(INK4a) and matrix metalloproteinase-1 (MMP-1) expression as markers of senescence. Compared with fetal tissue samples (n = 4), a significant increase in p16(INK4a)-positive astrocytes was observed in subjects aged 35 to 50 years (n = 6; P = 0.02) and 78 to 90 years (n = 11; P

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3440417?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/ff4588c5141641a39e02a1d9cb6d6b17Test

المؤلفون: Alessandro Bitto, Chad Lerner, Claudio Torres, Michaela Roell, Marco Malaguti, Viviana Perez, Antonello Lorenzini, Silvana Hrelia, Yuji Ikeno, Michelle Elizabeth Matzko, Roger McCarter, Christian Sell

المصدر: PLoS ONE, Vol 5, Iss 9, p e12592 (2010)

مصطلحات موضوعية: Medicine, Science

الوصف: A reduction in IGF-I signaling has been found to increase lifespan in multiple organisms despite the fact that IGF-I is a trophic factor for many cell types and has been found to have protective effects against multiple forms of damage in acute settings. The increase in longevity seen in response to reduced IGF-I signaling suggests that there may be differences between the acute and chronic impact of IGF-I signaling. We have examined the possibility that long-term stimulation with IGF-I may have a negative impact at the cellular level using quiescent human fibroblasts. We find that fibroblast cells exposed to IGF-I for 14 days have reduced long-term viability as judged by colony forming assays, which is accompanied by an accumulation of senescent cells. In addition we observe an accumulation of cells with depolarized mitochondria and a reduction in autophagy in the long-term IGF-I treated cultures. An examination of mice with reduced IGF-I levels reveals evidence of enhanced autophagy and fibroblast cells derived from these mice have a larger mitochondrial mass relative to controls indicating that changes in mitochondrial turnover occurs in animals with reduced IGF-I. The results indicate that chronic IGF-I stimulation leads to mitochondrial dysfunction and reduced cell viability.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC2935370?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/e420605603604e01bfb99bab7f48bf22Test