Areas of focus
Hypothalamus is a brain region known to regulate basic life functions, such as growth, development, reproduction, circadian rhythms, sleep and is critically involved in feeding, glucose homeostasis and metabolism. The hypothalamus neurons are capable to sense energy and peripheral signals (glucose, insulin, leptin), modifying energy status accordingly. Evidence suggests that the integrity of metabolic sensing mechanisms in hypothalamic neurons is crucial for maintaining metabolic homeostasis and normal aging. It is therefore exciting to suggest that hypothalamic neurons could drive aging and age-related diseases.
In our group we investigate the hypothalamus as an underlying mediator and a target for interventional strategies in counteracting aging and related diseases. In this context the group focuses the research on the following scientific questions and strategies: i) Does caloric restriction (CR) delay aging and age-related diseases through hypothalamus-related mechanisms? ii) Could we delay premature aging of Hutchinson Gilford progeria syndrome (HGPS) rodent models, and normal aging, by targeting the hypothalamus? iii) Hypothalamic changes related to obesity, depression and ageing.
• Caloric restriction and related mechanisms as anti-aging interventions and neuroprotector
• Changes in the hypothalamus induced by obesity and aging
• Hypothalamus has a target for preventing aging
• Neurogenesis in the Hypothalamus
• Changes in adipose tissue and hypothalamus induced by hypoxia: relation between sleep apnea syndrome, obesity and aging
• Endogenous caloric restriction mimetics and related mechanisms (NPY, ghrelin, sirtuins, ataxin-2) in hypothalamus.
Sara Carmo-Silva, Marisa Marques, André Carvalho, Dina Pereira, Patricia Valério, Célia Aveleira, Pedro Gomes, Cláudia Cavadas
• Studies on aging models and Hutchinson-Gilford Progeria Syndrome (HGPS) models.
Sara Carmo Silva, Marisa Marques, Dina Pereira, Célia Aveleira, Cláudia Cavadas
• MicroRNAs, neurogenesis and hypothalamic regulation.
André Carvalho, Sara Carmo Silva, Célia Aveleira, Cláudia Cavadas
• Sleep, obesity and aging
Laetitia Gaspar, Ana Rita Álvaro, Sara Carmo-Silva, Joana Rosmaninho-Salgado, Cláudia Cavadas
• Delaying neurodegeneration by NPY and caloric restriction approaches.
Cláudia Cavadas; collaboration with Luís Pereira de Almeida
Facilities and equipment
The lab is located at Rua Larga, Polo I, 2nd Floor – University of Coimbra. The lab is equipped with general cellular and molecular biology equipment. Researchers have access to cell culture rooms, animal facilities, rodent behavior room, microtome, fluorescence microscopy, scanning confocal microscopy, flow cytometry, electrophoresis apparatus, quantitative RT-PCR and HPLC.
Title: "Peripheral NPY reverts HGPS phenotype: a study in human fibroblasts and mouse model”. Grant Funded by Progeria Research Foundation (MA, USA). September 2015-August 2017
COST Action: An integrative action for multidisciplinary studies on cellular structural networks. COST Action. CA15214. National representative Cláudia Cavadas. 2016-2020
Title: “Ghrelin: a novel therapeutic intervention to rescue the phenotype of Hutchinson‐Gilford Progeria Syndrome”. American Progeria Research Foundation. 2015 –2016
Title: “Sleep apnea induces obesity: Why? What is the role of the hypothalamus and the adipose tissue?”. Grant International cooperation programmme: Fundação para a Ciência e a Tecnologia (Portugal) and CAPES (Brasil) “Entidade Financiadora: Fundação para a Ciência e a Tecnologia”. 2013-2015
Pre-clinical study of Depression - Pharmaceutical Company Contract- Tecnimed (Sintra, Portugal). 2013- 2014
Title: “iCALP - Identification of the physiological roles of calpains in the control of cell proliferation and migration in the central nervous system”. FCT project PTDC/SAU-NMC/112183/2009. 2011- 2014
Title: “Mechanisms underlying the effects of nitric oxide on neural stem cell proliferation in brain injury“. FCT project: PTDC/SAU-NEU/102612/2008. 2010- 2013
Title: “Caloric restriction increases lifespan: role of neuropeptide Y on autophagy”. FCT project: PTDC/SAU-FCF/099082/2008. April 2010-July 2013
Title: “Adenosine receptors on adrenal medulla regulation: its role on stress response”. FCT project: PTDC/SAU-NEU/108110/2008). 2010- 2013
Title: “The Neuropeptide Y (NPY) and Dipeptidyl-peptidase IV (DPPIV) as new promising targets on the adipose tissue regulation in obesity”. FCT project: PTDC/SAU‐FCF/102415/2008. 2010 – 2012
Title: "NPY in the retina: Why? and What for?”. FCT project: PTDC/SAU-NEU/73119/2006). 2007 - 2010
Title: "Evaluation of ecstasy toxicity in rat retina: in vitro and in vivo studies". Instituição Financiadora: "Gabinete de Apoio à Investigação" - Faculty of Medicine of the University of Coimbra. 2007
Title: "Crosstalk between catecholamines and neuropeptide Y in human chromaffin cells". FCT project POCTI/SAU-FCF/60399/2004. 2005 - 2008
Science and communication funded projects:
The Brains Go Around the Town” - Brain Awareness Week (BAW) March 2015. Federation of European Neuroscience Societies (FENS) funding.
Science Divulgation Project – “I want more and better cells! (Stem cells: What are they? Where are they? What are they used for?) COMPETE- Ciência viva; January 2011-December 2013
“Brain and mathematics” - Brain Awareness Week (BAW) March 2007; Federation of European Neuroscience Societies (FENS) funding.
Carlos Lopez Otin
Facultad de Medicina, Universidad de Oviedo, Oviedo, Spain
Harvard Medical School, USA
CHUC, Coimbra, Portugal
Glenn Laboratory for the Science of Aging, Massachusetts Institute of Technology, Cambridge, USA.
University of Campinas, Brazil
CIMUS, University of Santiago de Compostela, Spain
Item, Paris, France
IBILI, Faculty of Medicine, University of Coimbra, Portugal
Cunha-Santos J, Duarte-Neves J, Carmona V, Guarente L, Pereira de Almeida L* & Cavadas C*. Caloric restriction blocks neuropathology and motor deficits in Machado-Joseph disease mouse models through SIRT1 pathway. Nature Communications 2016, 7:11445.
Ferreira-Marques M, Aveleira CA, Carmo-Silva S, Botelho M, Pereira de Almeida L and Cavadas C. Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation. Aging (Albany NY) 2016, 8:1470-1484.
Cavadas C, Aveleira C, Souza G, Velloso L. Defective proteostasis in the hypothalamus A relevant pathophysiological mechanism from obesity to ageing. Nature Reviews Endocrinology 2016, 2(12):723-733.
Aveleira CA, Botelho M, Carmo-Silva S, Pascoal JF, Ferreira-Marques M, Nóbrega, C, Cortes L, Valero J, Sousa-Ferreira L, Álvaro AR, Santana M, Kügler S, Pereira de Almeida L, Cavadas C. Neuropeptide Y stimulates autophagy in hypothalamic neurons. PNAS 2015, 112(13): E1642-E1651
Botelho M & Cavadas C. Neuropeptide Y: an anti-aging player? Trends in Neurosciences 2015, 38(11):701-11
Faculty of Pharmacy
University of Coimbra
Ph: +351 963928766