Neuroscience and Disease

Hypothalamus: a target to delay aging and age-related diseases



Neuroendocrine peptides


Cellular senescence

Research lines

Hypothalamic control of Aging

Caloric restriction and related mechanisms as anti-Aging interventions

Neuroendocrine peptides as novel therapeutic interventions to delay aging and age-related disease, including Hutchinson-Gilford Progeria Syndrome, a premature aging disease


Human life expectancy is increasing and so too the socioeconomic burden of age-related diseases. Although the molecular mechanisms underlying aging remain an extremely active area of research, their exact nature remains obscure. Understanding the biological bases of aging is utmost important to future genetic/pharmacological interventions to ameliorate age-related deteriorations and promote a “healthy” and active aging. In recent years hypothalamus has emerged as a key player in whole-body aging. This brain region regulates body homeostasis through specialized neurons that sense and integrate central and peripheral signals to properly coordinate several survival functions, including development, reproduction, circadian rhythms, food intake, metabolism and neuroendocrine axis. Therefore, a decline in hypothalamic neurons responsiveness with age may adversely affect body physiological functions. In line with this, we are focused on better understand the molecular and cellular mechanisms underlying aging and how hypothalamus regulates whole-body aging with the ultimate goal of finding new therapeutic targets to delay the aging process of normal and premature aging diseases and improve “healthy” aging. In our group we use both in vitro and in vivo experimental models and a combination of molecular, cellular, and histological techniques with behavior and bioinformatics analysis to better understand the mechanisms underlying the aging process.


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Information about journal articles, updated at 15-05-2022, from platform CIÊNCIAVITAE.

Enhancing ghrelin signaling alleviates aging and extends lifespan of a mouse model of human accelerated aging syndrome (under submission).

Ferreira-Marques, M (EA15-6C9F-F15E); Carvalho, A; Franco, Ana Catarina; Leal, A; Botelho, M; Carmo-Silva, Sara; Águas, R; et al, 2022. 2022. submitted

Ataxin-2 in the hypothalamus at the crossroads between metabolism & circadian rhythm (under revision)

Carmo-Silva, Sara; Ferreira-Marques, M (EA15-6C9F-F15E); Nóbrega, Clévio David Rodrigues ; Botelho M; Costa, D; Aveleira C; Pulst, Stefan; Almeida, Luís Pereira de; Cavadas, Claudia, 2022. Journal of Molecular Endocrinology. 2022. under revision Journal of Molecular Endocrinology

Leptin enhances progerin clearance and ameliorates the senescent phenotype of human Hutchinson-Gilford Progeria Syndrome cells (under submission))

Real, AC; Ferreira-Marques, M (EA15-6C9F-F15E); Cortes, Luisa; Cavadas, Cláudia (D413-2E77-4BDE); Aveleira, Célia A (651B-75AE-BD02), 2022. 2022. submitted

Skin senescence: mechanisms and impact on whole-body aging

Ana Catarina Franco; Aveleira C; Cavadas, Claudia, 2022. Trends Molecular Medicine. 97 - 109. 2. 28. 2022. published Trends Molecular Medicine

Cellular senescence mechanisms in the context of current biomarkers and senotherapies (under submission)

Vasco Lucas; Claudia Cavadas; Aveleira C, 2022. Pharmacological Reviews. 2022. submitted Pharmacological Reviews

PI3K/AKT/MTOR and ERK1/2/MAPK signaling pathways are involved in autophagy stimulation induced by caloric restriction or caloric restriction mimetics in cortical neurons.

Ferreira-Marques, Marisa (EA15-6C9F-F15E); Carvalho, A; Cavadas, Cláudia (D413-2E77-4BDE); Aveleira, Célia A (651B-75AE-BD02), 2021. Aging. 2021. accepted Aging

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Klionsky D J; Abdel-Aziz A K; ...; Aveleira C; Chun-Kit Tong, 2021. Autophagy. 2021. . published Autophagy

Neuropeptide Y Enhances Progerin Clearance and Ameliorates the Senescent Phenotype of Human Hutchinson-Gilford Progeria Syndrome Cells.

Aveleira, Célia A; Ferreira-Marques, Marisa; Cortes, Luísa; Valero, Jorge; Pereira, Dina; Pereira de Almeida, Luís; Cavadas, Cláudia, 2020. The Journals of Gerontology: Series A. 2020. . 10.1093/gerona/glz280 . published The Journals of Gerontology: Series A

Elevated Glucose and Interleukin-1ß Differentially Affect Retinal Microglial Cell Proliferation

Baptista, Filipa I.; Aveleira, Célia A.; Castilho, Áurea F.; Ambrósio, António F., 2017. Mediators of Inflammation. 1 - 11. 2017. 2017. . 10.1155/2017/4316316 . published Mediators of Inflammation

The pathophysiology of defective proteostasis in the hypothalamus - from obesity to ageing

Cavadas, Cláudia; Aveleira, Célia A.; Souza, Gabriela F. P.; Velloso, Lício A., 2016. Nature Reviews Endocrinology. 723 - 733. 12. 12. 2016. . 10.1038/nrendo.2016.107 . published Nature Reviews Endocrinology

Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation

Ferreira-Marques, Marisa; Aveleira, Célia A.; Carmo-Silva, Sara; Botelho, Mariana; Pereira de Almeida, Luís; Cavadas, Cláudia, 2016. Aging. 1470 - 1484. 7. 8. 2016. . 10.18632/aging.100996 . published Aging

Impaired adrenal medullary function in a mouse model of depression induced by unpredictable chronic stress

Santana, Magda M.; Rosmaninho-Salgado, Joana; Cortez, Vera; Pereira, Frederico C.; Kaster, Manuella P.; Aveleira, Célia A.; Ferreira, Marisa; Álvaro, Ana Rita; Cavadas, Cláudia, 2015. European Neuropsychopharmacology. 1753 - 1766. 10. 25. 2015. . 10.1016/j.euroneuro.2015.06.013 . published European Neuropsychopharmacology

Neuropeptide Y stimulates autophagy in hypothalamic neurons

Aveleira, Célia A.; Botelho, Mariana; Carmo-Silva, Sara; Pascoal, Jorge F.; Ferreira-Marques, Marisa; Nóbrega, Clévio; Cortes, Luísa; et al, 2015. Proceedings of the National Academy of Sciences. E1642 - E1651. 13. 112. 2015. . 10.1073/pnas.1416609112 . published Proceedings of the National Academy of Sciences

NPY/neuropeptide Y enhances autophagy in the hypothalamus: a mechanism to delay aging?

Aveleira, Célia A; Botelho, Mariana; Cavadas, Cláudia, 2015. Autophagy. 1431 - 1433. 8. 11. 2015. . 10.1080/15548627.2015.1062202 . Autophagy

Long-term exposure to high glucose increases the content of several exocytotic proteins and of vesicular GABA transporter in cultured retinal neural cells

Baptista, Filipa I.; Castilho, Áurea F.; Gaspar, Joana M.; Liberal, Joana T.; Aveleira, Célia A.; Ambrósio, António F., 2015. Neuroscience Letters. 56 - 61. 602. 2015. . 10.1016/j.neulet.2015.06.044 . published Neuroscience Letters

Alterations in phospholipidomic profile in the brain of mouse model of depression induced by chronic unpredictable stress

Faria, R.; Santana, M.M.; Aveleira, C.A.; Simões, C.; Maciel, E.; Melo, T.; Santinha, D.; et al, 2014. Neuroscience. 1 - 11. 273. 2014. . 10.1016/j.neuroscience.2014.04.042 . published Neuroscience

Fluoxetine Induces Proliferation and Inhibits Differentiation of Hypothalamic Neuroprogenitor Cells In Vitro

Sousa-Ferreira, Lígia; Aveleira, Célia; Botelho, Mariana; Álvaro, Ana Rita; Pereira de Almeida, Luís; Cavadas, Cláudia, 2014. PLoS ONE. 3. 9. 2014. . 10.1371/journal.pone.0088917 . published PLoS ONE

Beclin 1 mitigates motor and neuropathological deficits in genetic mouse models of Machado–Joseph disease

Nascimento-Ferreira, Isabel; Nóbrega, Clévio; Vasconcelos-Ferreira, Ana; Onofre, Isabel; Albuquerque, David; Aveleira, Célia; Hirai, Hirokazu; Déglon, Nicole; Pereira de Almeida, Luís, 2013. Brain. 2173 - 2188. 7. 136. 2013. . 10.1093/brain/awt144 . published Brain

Neuropeptide Y Receptors Y1 and Y2 are Present in Neurons and Glial Cells in Rat Retinal Cells in Culture

Santos-Carvalho, Ana; Aveleira, Célia A.; Elvas, Filipe; Ambrósio, António Francisco; Cavadas, Cláudia, 2013. Investigative Opthalmology & Visual Science. 1. 54. 2013. . 10.1167/iovs.12-10776 . published Investigative Opthalmology & Visual Science

Heme Oxygenase-1 Protects Retinal Endothelial Cells against High Glucose- and Oxidative/Nitrosative Stress-Induced Toxicity

Castilho, Áurea F.; Aveleira, Célia A.; Leal, Ermelindo C.; Simões, Núria F.; Fernandes, Carolina R.; Meirinhos, Rita I.; Baptista, Filipa I.; Ambrósio, António F., 2012. PLoS ONE. 8. 7. 2012. . 10.1371/journal.pone.0042428 . published PLoS ONE

Proliferative Hypothalamic Neurospheres Express NPY, AGRP, POMC, CART and Orexin-A and Differentiate to Functional Neurons

Sousa-Ferreira, Lígia; Álvaro, Ana Rita; Aveleira, Célia; Santana, Magda; Brandão, Inês; Kügler, Sebastian; Pereira de Almeida, Luís; Cavadas, Cláudia, 2011. PLoS ONE. 5. 6. 2011. . 10.1371/journal.pone.0019745 . published PLoS ONE

High glucose and interleukin-1ß downregulate interleukin-1 type I receptor (IL-1RI) in retinal endothelial cells by enhancing its degradation by a lysosome-dependent mechanism

Aveleira, Célia; Castilho, Áurea; Baptista, Filipa; Simões, Núria; Fernandes, Carolina; Leal, Ermelindo; Ambrósio, António Francisco, 2010. Cytokine. 279 - 286. 3. 49. 2010. . 10.1016/j.cyto.2009.11.014 . published Cytokine

TNF-  Signals Through PKCz /NF- kB to Alter the Tight Junction Complex and Increase Retinal Endothelial Cell Permeability

Aveleira, C. A.; Lin, C.-M.; Abcouwer, S. F.; Ambrosio, A. F.; Antonetti, D. A., 2010. Diabetes. 2872 - 2882. 11. 59. 2010. . 10.2337/db09-1606 . published Diabetes

High glucose and oxidative/nitrosative stress conditions induce apoptosis in retinal endothelial cells by a caspase-independent pathway

Leal, Ermelindo C.; Aveleira, Célia A.; Castilho, Áurea F.; Serra, Andreia M.; Baptista, Filipa I.; Hosoya, Ken-Ichi; Forrester, John V.; Ambrósio, António F., 2009. Experimental Eye Research. 983 - 991. 5. 88. 2009. . 10.1016/j.exer.2008.12.010 . published Experimental Eye Research

Müller Cells Do Not Influence Leukocyte Adhesion to Retinal Endothelial Cells

Leal, Ermelindo C.; Aveleira, Célia A.; Castilho, Aurea F.; Baptista, Filipa I.; Ambrósio, António F., 2008. Ocular Immunology and Inflammation. 173 - 179. 4. 16. 2008. . 10.1080/09273940802204535 . published Ocular Immunology and Inflammation

NPY in rat retina is present in neurons, in endothelial cells and also in microglial and Müller cells

Álvaro, Ana Rita; Rosmaninho-Salgado, Joana; Santiago, Ana Raquel; Martins, João; Aveleira, Célia; Santos, Paulo F.; Pereira, Tiago; et al, 2007. Neurochemistry International. 757 - 763. 5. 50. 2007. . 10.1016/j.neuint.2007.01.010 . published Neurochemistry International



Janssen Inovação Award (2nd place)

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