Cláudia Cavadas is PharmD, Master in Cell Biology, and PhD in Pharmacology (2002), University of Coimbra. During her PhD, she spent 3 years at the Division of Hypertension, CHUV, Lausanne, Switzerland. Since 2002, she is Associate professor, at the Faculty of Pharmacy of the University of Coimbra and Group Leader of “Neuroendocrinology and Aging group” at CNC - Center for Neuroscience and Cell Biology. Recently, her group has been investigating the hypothalamus and the impact of neuropeptides on aging and age related mechanisms. Cláudia Cavadas has 100 publications. She was the principal investigator of 20 funded projects. She was supervisor of around 50 graduate students . that already finished the thesis. She was Vice-rector oof the University of Coimbra (2019 - 2023) and Director of Institute for Interdisciplinary Research of the University of Coimbra. She is the former President of the Portuguese Society of Pharmacology. At the Faculty of Pharmacy, Cláudia Cavadas is professor of Pharmacology, Science Communication, Pathophysiology, Histology and Human Embryology. See more information at:https://www.cnc.uc.pt/en/people/c-cavadas
Investigative Ophthalmology & Visual Science, Jun 16, 2013
9:05-9:20am Efemp1 R345W causes amplified melanopsin responses to light that are propoagated amon... more 9:05-9:20am Efemp1 R345W causes amplified melanopsin responses to light that are propoagated among multiple RGC types
Introduction: Aging has been considered a risk factor for Obstructive Sleep Apnea (OSA) developme... more Introduction: Aging has been considered a risk factor for Obstructive Sleep Apnea (OSA) development. Untreated OSA has been associated with alterations that resemble the typical physiological and functional decline observed along the aging process. Aim: Evaluate how OSA might aggravate/promote aging through alteration in mitochondrial bioenergetics in OSA patients’ peripheral blood cells and to assess the impact of OSA treatment. Methods: A cohort of 17 OSA adult male patients was followed from the moment of their diagnosis (polysomnography), up to 4 months and 24 months of treatment with continuous positive airway pressure (CPAP) and compared with healthy subjects (age-matched and young controls). Results: OSA patients’ blood samples show decreased levels of mRNA/ protein mitochondrial fusion markers (pl0.01), a decreased tendency in mitochondrial complexes associated subunits expression and mitochondrial biogenesis impairment (p=0.08) in comparison with healthy control subjects, an effect that does not ameliorate after 24 months treatment. In addition, circulating levels of C-reactive protein (CRP) shows disruptions in OSA patients’ serum levels that are partially reverted upon OSA treatment. Conclusion: OSA aggravates/promotes dysfunctional mitochondria alterations and an inflammatory process, which can contribute to aging and directly impact on cellular signalling and inter organelle crosstalk. Most of these alterations are not reverted upon CPAP treatment, reinforcing the urgent need of new approaches for OSA diagnosis and treatment.
Machado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder char... more Machado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder characterized by an over-repetition of the CAG trinucleotide of theATXN3gene, conferring a toxic gain-of-function to the resulting ataxin-3 protein. Despite the significant advances produced over the last years, the molecular mechanisms involved in MJD are still unclear and no treatment able to modify the disease progression is available. Aging is the major risk factor for neurodegenerative disorders, being associated with the occurrence and progression of several diseases, such as Alzheimer’s, Huntington’s, among others. The nuclear membrane proteins - lamins - and lamin-processing related proteins, such as ZMPSTE24, have been shown to be altered, not only during normal aging, but also in neurodegenerative disorders, such as Alzheimer’s disease.Taking this into account, we aimed at investigating the role of aging in MJD by evaluating the presence of age-related markers in human and animal M...
Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a ... more Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a single nucleotide alteration in theLMNAgene, which leads to the production of a defective lamin A protein known as progerin. The buildup of progerin hastens the onset of premature and expedited aging. Patients with HGPS exhibit short stature, low body weight, lipodystrophy, metabolic dysfunction, and skin and musculoskeletal abnormalities and, in most cases, die of cardiovascular disease by their early teenage years. Currently, no effective cure or treatment for the disease highlights the importance of discovering new therapeutic strategies. Herein, we present evidence that the hormone ghrelin, besides promoting autophagy and progerin clearance, rescued several cellular hallmarks of premature aging of human HGPS fibroblasts. Using an HGPS mouse model,LmnaG609G/G609Gmice, we also show that ghrelin administration rescued the short-lived mice molecular and histopathological progeroid featur...
Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a ... more Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a single nucleotide alteration in theLMNAgene, which leads to the production of a defective lamin A protein known as progerin. The buildup of progerin hastens the onset of premature and expedited aging. Patients with HGPS exhibit short stature, low body weight, lipodystrophy, metabolic dysfunction, and skin and musculoskeletal abnormalities and, in most cases, die of cardiovascular disease by their early teenage years. Currently, no effective cure or treatment for the disease highlights the importance of discovering new therapeutic strategies. Herein, we present evidence that the hormone ghrelin, besides promoting autophagy and progerin clearance, rescued several cellular hallmarks of premature aging of human HGPS fibroblasts. Using an HGPS mouse model,LmnaG609G/G609Gmice, we also show that ghrelin administration rescued the short-lived mice molecular and histopathological progeroid featur...
Introduction: Obstructive Sleep Apnea (OSA), one of the most common sleep disorders worldwide has... more Introduction: Obstructive Sleep Apnea (OSA), one of the most common sleep disorders worldwide has been suggested to promote aging by inducing cellular and molecular aging mechanisms (Gaspar, et al. 2017). Understanding OSA putative effect on aging might contribute to understand new strategies to improve OSA diagnosis and treatment but also to counteract aging. Aim: To investigate cellular senescence and senescent associate secretory phenotype (SASP), a hallmark of aging, in OSA patients and the impact of OSA treatment. Methods: A cohort of 9 adult male patients diagnosed with severe OSA was followed from the moment of diagnosis with polysomnography (PSG), up to 4 months and 24 months of treatment with continuous pressure positive mask (CPAP). SASP biomarkers were evaluated in OSA patients in comparison to age-matched controls and younger controls, both validated by PSG. Results: OSA patients show a deregulation of pro- and anti-inflammatory cytokine levels, in comparison with age-ma...
Background Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most... more Background Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model. Methods Two MJD animal models, a lentiviral based and a transgenic model, were orally treated with 2% trehalose solution for a period of 4 and 30 weeks, respectively. Motor behavior (rotarod, grip strength and footprint patterns) was evaluated at different time points and neuropathological features were evaluated upon in-life phase termination. Results Trehalose-treated MJD mice equilibrated for a longer time in the rotarod apparatus and exh...
Teaser: The circadian clock is essential for the regulation of physiological processes. Circadian... more Teaser: The circadian clock is essential for the regulation of physiological processes. Circadian disruption can lead to serious pathological consequences. This comprehensive review focuses on novel clock modulators and their therapeutic potential against various diseases. Disruption of circadian oscillations has a wide-ranging impact on health, with the potential to induce the development of clock-related diseases. Small-molecule modulators of the circadian clock (SMMCC) target core or noncore clock proteins, modulating physiological effects as a consequence of agonist, inverse agonist, or antagonist interference. These pharmacological modulators are usually identified using chemical screening of large libraries of active compounds. However, target-based screens, chemical optimization, and circadian crystallography have recently assisted in the identification of these compounds. In this review, we focus on established and novel SMMCCs targeting both core and noncore clock proteins, identifying their circadian targets, detailed circadian effects, and specific physiological effects. In addition, we discuss their therapeutic potential for the treatment of diverse clock-related disorders (such as metabolic-associated disorders, autoimmune diseases, mood disorders, and cancer) and as chronotherapeutics. Future perspectives are also considered, such as clinical trials, and potential safety hazards, including those in the absence of clinical trials.
Background We previously described protective effects of blueberry juice (BJ) against hepatic ste... more Background We previously described protective effects of blueberry juice (BJ) against hepatic steatosis evolution in a hypercaloric diet-induced rat model of prediabetes; however, the underlying mechanisms, are still scarcely explored. Herein, we aim to elucidate the molecular pathways underpinning BJ hepatoprotection on the dysmetabolism evolution in a rat model of prediabetes. Methods A rat model of evolutive prediabetes [Male Wistar rats, 8 weeks old] was developed by ingestion of a high-sucrose (HSu, 35%) diet for 9 weeks (W9), supplemented with a high-fat diet (HF, 60%) for further 14 weeks (HSuHF, W23), vs control with standard diet. Half of the animals (n = 10/group) daily received BJ (25g/Kg BW, orally) between W9 and W23. Along with metabolic characterization, BJ effects on serum and hepatic metabolic surrogates were elucidated using a 1H NMR based metabolomic approach. Moreover, the liver expression of genes (RT-PCR) involved in insulin signaling, lipid metabolism, inflamm...
Investigative Ophthalmology & Visual Science, Jun 16, 2013
9:05-9:20am Efemp1 R345W causes amplified melanopsin responses to light that are propoagated amon... more 9:05-9:20am Efemp1 R345W causes amplified melanopsin responses to light that are propoagated among multiple RGC types
Introduction: Aging has been considered a risk factor for Obstructive Sleep Apnea (OSA) developme... more Introduction: Aging has been considered a risk factor for Obstructive Sleep Apnea (OSA) development. Untreated OSA has been associated with alterations that resemble the typical physiological and functional decline observed along the aging process. Aim: Evaluate how OSA might aggravate/promote aging through alteration in mitochondrial bioenergetics in OSA patients’ peripheral blood cells and to assess the impact of OSA treatment. Methods: A cohort of 17 OSA adult male patients was followed from the moment of their diagnosis (polysomnography), up to 4 months and 24 months of treatment with continuous positive airway pressure (CPAP) and compared with healthy subjects (age-matched and young controls). Results: OSA patients’ blood samples show decreased levels of mRNA/ protein mitochondrial fusion markers (pl0.01), a decreased tendency in mitochondrial complexes associated subunits expression and mitochondrial biogenesis impairment (p=0.08) in comparison with healthy control subjects, an effect that does not ameliorate after 24 months treatment. In addition, circulating levels of C-reactive protein (CRP) shows disruptions in OSA patients’ serum levels that are partially reverted upon OSA treatment. Conclusion: OSA aggravates/promotes dysfunctional mitochondria alterations and an inflammatory process, which can contribute to aging and directly impact on cellular signalling and inter organelle crosstalk. Most of these alterations are not reverted upon CPAP treatment, reinforcing the urgent need of new approaches for OSA diagnosis and treatment.
Machado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder char... more Machado-Joseph disease (MJD) is an autosomal dominantly-inherited neurodegenerative disorder characterized by an over-repetition of the CAG trinucleotide of theATXN3gene, conferring a toxic gain-of-function to the resulting ataxin-3 protein. Despite the significant advances produced over the last years, the molecular mechanisms involved in MJD are still unclear and no treatment able to modify the disease progression is available. Aging is the major risk factor for neurodegenerative disorders, being associated with the occurrence and progression of several diseases, such as Alzheimer’s, Huntington’s, among others. The nuclear membrane proteins - lamins - and lamin-processing related proteins, such as ZMPSTE24, have been shown to be altered, not only during normal aging, but also in neurodegenerative disorders, such as Alzheimer’s disease.Taking this into account, we aimed at investigating the role of aging in MJD by evaluating the presence of age-related markers in human and animal M...
Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a ... more Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a single nucleotide alteration in theLMNAgene, which leads to the production of a defective lamin A protein known as progerin. The buildup of progerin hastens the onset of premature and expedited aging. Patients with HGPS exhibit short stature, low body weight, lipodystrophy, metabolic dysfunction, and skin and musculoskeletal abnormalities and, in most cases, die of cardiovascular disease by their early teenage years. Currently, no effective cure or treatment for the disease highlights the importance of discovering new therapeutic strategies. Herein, we present evidence that the hormone ghrelin, besides promoting autophagy and progerin clearance, rescued several cellular hallmarks of premature aging of human HGPS fibroblasts. Using an HGPS mouse model,LmnaG609G/G609Gmice, we also show that ghrelin administration rescued the short-lived mice molecular and histopathological progeroid featur...
Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a ... more Hutchinson-Gilford progeria syndrome (HGPS) is a rare and fatal genetic condition arising from a single nucleotide alteration in theLMNAgene, which leads to the production of a defective lamin A protein known as progerin. The buildup of progerin hastens the onset of premature and expedited aging. Patients with HGPS exhibit short stature, low body weight, lipodystrophy, metabolic dysfunction, and skin and musculoskeletal abnormalities and, in most cases, die of cardiovascular disease by their early teenage years. Currently, no effective cure or treatment for the disease highlights the importance of discovering new therapeutic strategies. Herein, we present evidence that the hormone ghrelin, besides promoting autophagy and progerin clearance, rescued several cellular hallmarks of premature aging of human HGPS fibroblasts. Using an HGPS mouse model,LmnaG609G/G609Gmice, we also show that ghrelin administration rescued the short-lived mice molecular and histopathological progeroid featur...
Introduction: Obstructive Sleep Apnea (OSA), one of the most common sleep disorders worldwide has... more Introduction: Obstructive Sleep Apnea (OSA), one of the most common sleep disorders worldwide has been suggested to promote aging by inducing cellular and molecular aging mechanisms (Gaspar, et al. 2017). Understanding OSA putative effect on aging might contribute to understand new strategies to improve OSA diagnosis and treatment but also to counteract aging. Aim: To investigate cellular senescence and senescent associate secretory phenotype (SASP), a hallmark of aging, in OSA patients and the impact of OSA treatment. Methods: A cohort of 9 adult male patients diagnosed with severe OSA was followed from the moment of diagnosis with polysomnography (PSG), up to 4 months and 24 months of treatment with continuous pressure positive mask (CPAP). SASP biomarkers were evaluated in OSA patients in comparison to age-matched controls and younger controls, both validated by PSG. Results: OSA patients show a deregulation of pro- and anti-inflammatory cytokine levels, in comparison with age-ma...
Background Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most... more Background Machado–Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is the most common of the dominantly inherited ataxias worldwide and is characterized by mutant ataxin-3 aggregation and neuronal degeneration. There is no treatment available to block or delay disease progression. In this work we investigated whether trehalose, a natural occurring disaccharide widely used in food and cosmetic industry, would rescue biochemical, behavioral and neuropathological features of an in vitro and of a severe MJD transgenic mouse model. Methods Two MJD animal models, a lentiviral based and a transgenic model, were orally treated with 2% trehalose solution for a period of 4 and 30 weeks, respectively. Motor behavior (rotarod, grip strength and footprint patterns) was evaluated at different time points and neuropathological features were evaluated upon in-life phase termination. Results Trehalose-treated MJD mice equilibrated for a longer time in the rotarod apparatus and exh...
Teaser: The circadian clock is essential for the regulation of physiological processes. Circadian... more Teaser: The circadian clock is essential for the regulation of physiological processes. Circadian disruption can lead to serious pathological consequences. This comprehensive review focuses on novel clock modulators and their therapeutic potential against various diseases. Disruption of circadian oscillations has a wide-ranging impact on health, with the potential to induce the development of clock-related diseases. Small-molecule modulators of the circadian clock (SMMCC) target core or noncore clock proteins, modulating physiological effects as a consequence of agonist, inverse agonist, or antagonist interference. These pharmacological modulators are usually identified using chemical screening of large libraries of active compounds. However, target-based screens, chemical optimization, and circadian crystallography have recently assisted in the identification of these compounds. In this review, we focus on established and novel SMMCCs targeting both core and noncore clock proteins, identifying their circadian targets, detailed circadian effects, and specific physiological effects. In addition, we discuss their therapeutic potential for the treatment of diverse clock-related disorders (such as metabolic-associated disorders, autoimmune diseases, mood disorders, and cancer) and as chronotherapeutics. Future perspectives are also considered, such as clinical trials, and potential safety hazards, including those in the absence of clinical trials.
Background We previously described protective effects of blueberry juice (BJ) against hepatic ste... more Background We previously described protective effects of blueberry juice (BJ) against hepatic steatosis evolution in a hypercaloric diet-induced rat model of prediabetes; however, the underlying mechanisms, are still scarcely explored. Herein, we aim to elucidate the molecular pathways underpinning BJ hepatoprotection on the dysmetabolism evolution in a rat model of prediabetes. Methods A rat model of evolutive prediabetes [Male Wistar rats, 8 weeks old] was developed by ingestion of a high-sucrose (HSu, 35%) diet for 9 weeks (W9), supplemented with a high-fat diet (HF, 60%) for further 14 weeks (HSuHF, W23), vs control with standard diet. Half of the animals (n = 10/group) daily received BJ (25g/Kg BW, orally) between W9 and W23. Along with metabolic characterization, BJ effects on serum and hepatic metabolic surrogates were elucidated using a 1H NMR based metabolomic approach. Moreover, the liver expression of genes (RT-PCR) involved in insulin signaling, lipid metabolism, inflamm...
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