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Front Cover -- Aging -- Copyright Page -- Contents -- List of contributors -- Foreword -- Preface -- 1 The societal burden of aging -- 1 Global aging and health determinants in a changing world -- 1.1 Introduction -- 1.2 The geographies of a global trend -- 1.2.1 Global patterns and projections -- 1.2.2 Multiscale intraregional variations of the aging process -- 1.3 Environmental health in later life -- 1.3.1 From successful aging to the role of place and inequities -- 1.3.2 How environment affects physical health in old age -- 1.3.3 The subjective experience of place: place attachment and residential normalcy -- 1.4 Global stressors in a changing world -- 1.4.1 Welfare state and neoliberalism -- 1.4.2 Climate change and health in old age -- 1.4.3 Migrations and health in old age -- 1.4.4 Discrimination as a health issue for older persons -- 1.5 Conclusion -- Acknowledgments -- References -- 2 Flagship initiatives for healthy living and active aging in Europe: the European Innovation Partnership on Active and Hea... -- 2.1 Demographic changes and aging -- 2.2 The European Innovation Partnership on Active and Healthy Ageing -- 2.2.1 European Innovation Partnership on Active and Healthy Ageing cross-cutting initiatives -- 2.3 Reference sites-case studies -- 2.3.1 Ageing@Coimbra Reference Site -- 2.3.2 The Healthy Ageing Network Northern Netherlands -- 2.3.3 Valencia region Reference Site -- 2.3.4 Andalusia Reference Site -- 2.3.5 The Lodz4Generations Reference Site -- 2.3.6 Campania Reference Site (ProMIS network) -- 2.3.7 MACVIA-France Reference Site -- 2.4 Reference Site Collaborative Network -- 2.5 Transition from Horizon 2020 to Horizon Europe-the role of IN-4-Active and Healthy Ageing -- 2.6 Future perspectives -- Acknowledgment -- References -- 3 Aging in Africa, challenges and opportunities-the particular case of Cabo Verde.

Sanguinarine is a natural isoquinoline alkaloid derived from the root of Sanguinaria canadensis and from other poppy fumaria species, and is known to have a broad spectrum of pharmacological properties. Here we have found that sanguinarine, at low micromolar concentrations, showed a remarkably rapid killing activity against human melanoma cells. Time-lapse videomicroscopy showed rapid morphological changes compatible with an apoptotic cell death, which was further supported by biochemical markers, including caspase activation, poly(ADP-ribose) polymerase (PARP) cleavage and DNA breakdown. Pan-caspase inhibition blocked sanguinarine-induced cell death. Sanguinarine treatment also induced an increase in intracellular calcium concentration, which was inhibited by dantrolene, and promoted cleavage of BAP-31, thus suggesting a putative role for Ca2+ release from endoplasmic reticulum and a cross-talk between endoplasmic reticulum and mitochondria in the anti-melanoma action of sanguinarine. Sanguinarine disrupted the mitochondrial transmembrane potential (ΔΨm), released cytochrome c and Smac/DIABLO from mitochondria to cytosol, and induced oxidative stress. Overexpression of Bcl-XL by gene transfer did not prevent sanguinarine-mediated cell death, oxidative stress or release of mitochondrial apoptogenic proteins. However, preincubation with N-acetyl-l-cysteine (NAC) prevented sanguinarine-induced oxidative stress, PARP cleavage, release of apoptogenic mitochondrial proteins, and cell death. Pretreatment with glutathione (GSH) also inhibited the anti-melanoma activity of sanguinarine. Thus, pretreatment with the thiol antioxidants NAC and GSH abrogated the killing activity of sanguinarine. Taking together, our data indicate that sanguinarine is a very rapid inducer of human melanoma caspase-dependent cell death that is mediated by oxidative stress. © 2013 Elsevier B.V. ; This work was supported by grants from Fundação para a Ciência e a Tecnologia (FCT) (PTDC/QUI-QUI/101409/2008 and PEst-C/SAU/LA0001/2011 co-funded by Feder/Compete/National Funds) to P.J.O.; Ministerio de Economía y Competitividad of Spain (SAF2008-02251, SAF2011-30518), Red Temática de Investigación Cooperativa en Cáncer, Instituto de Salud Carlos III, cofunded by the Fondo Europeo de Desarrollo Regional of the European Union (RD06/0020/1037 and RD12/0036/0065) to F.M.; Fondo de Investigación Sanitaria and European Commission (PS09/01915) to C.G.; Junta de Castilla y León (CSI052A11-2, CSI221A12-2, GR15-Experimental Therapeutics and Translational Oncology Program, and Biomedicine Project 2010-2011) to F.M and C.G. A.B. was recipient of a predoctoral fellowship from the Portuguese FCT (SFRH/BD/32943/2006). C.G. was supported by the Ramón y Cajal Program from the Spanish Ministerio de Ciencia e Innovación. ; Peer Reviewed

Work in the laboratories of the authors is funded by FEDER funds through the Operational Programme Competitiveness Factors—COMPETE and national funds by FCT—Foundation for Science and Technology (PTDC/BTM-SAL/29297/2017, POCI-01-0145-FEDER-029297, PTDC/MED-FAR/29391/2017, POCI-01-0145-FEDER-029391, IF/01182/2015 and UIDB/04539/2020). iNOVA4Health-UID/Multi/04462/2013, a program financially supported by Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência, through national funds and co-funded by FEDER under the PT2020 Partnership Agreement, is acknowledged. Guida Bento is the recipient of a Ph.D. fellowship from the Foundation for Science and Technology (PD/BD/114119/2015). AKS and AAR were funded by the subsidy allocated to Kazan Federal University for the state assignment in the sphere of scientific activities. Kazan Federal University was supported by the Russian Government Program of Competitive Growth. ; Despite being a biological waste, human urine contains a small population of cells with self-renewal capacity and differentiation potential into several cell types. Being derived from the convoluted tubules of nephron, renal pelvis, ureters, bladder and urethra, urine-derived stem cells (UDSC) have a similar phenotype to mesenchymal stroma cells (MSC) and can be reprogrammed into iPSC (induced pluripotent stem cells). Having simple, safer, low-cost and noninvasive collection procedures, the interest in UDSC has been growing in the last decade. With great potential in regenerative medicine applications, UDSC can also be used as biological models for pharmacology and toxicology tests. This review describes UDSC biological characteristics and differentiation potential and their possible use, including the potential of UDSC-derived iPSC to be used in drug discovery and toxicology, as well as in regenerative medicine. Being a new cellular platform amenable to noninvasive collection for disease stratification and personalized therapy could be a future application for UDSC. ; publishersversion ; published

Triterpenoids are a large class of naturally occurring compounds, and some potentially interesting as anticancer agents have been found to target mitochondria. The objective of the present work was to investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP) derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma cells in vitro. MCF-7, Hs 578T and BJ cell lines, as well as isolated hepatic mitochondria, were used to investigate direct mitochondrial effects. On isolated mitochondrial hepatic fractions, respiratory parameters, mitochondrial transmembrane electric potential, induction of the mitochondrial permeability transition (MPT) pore and ion transport-dependent osmotic swelling were measured. Our results indicate that the DMAP triterpenoid derivatives lead to fragmentation and depolarization of the mitochondrial network in situ, and to inhibition of uncoupled respiration, induction of the permeability transition pore and depolarization of isolated hepatic mitochondria. The results show that mitochondrial toxicity is an important component of the biological interaction of DMAP derivatives, which can explain the effects observed in cancer cells. ; This work was supported by projects Pest-C/SAU/LA0001/2013– 2014 and PTDC/QUI-QUI/101409/2008 funded by Fundação para a Ciência e a Tecnologia (FCT), Portugal, and cofinanced by: 'COMPETE- Programa Operacional Factores de Competitividade', QREN and European Union (FEDER-Fundo Europeu de Desenvolvimento Regional). T.C.-O. was supported by the FCT postdoctoral fellowship SFRH/BPD/34711/2007, T.L.S. supported by the FCT postdoctoral fellowship SFRH/BPD/75959/2011, both co-financed by POPHPrograma Operacional Potencial Humano, QREN and European Union.