RESUMEN
Age-related diseases are associated with increased morbidity in the past few decades and the cost associated with the treatment of these age-related diseases exerts a substantial impact on social and health care expenditure. Anti-aging strategies aim to mitigate, delay and reverse aging-associated diseases, thereby improving quality of life and reducing the burden of age-related pathologies. The natural dietary antioxidant supplementation offers substantial pharmacological and therapeutic effects against various disease conditions. Astaxanthin is one such natural carotenoid with superior antioxidant activity than other carotenoids, as well as well as vitamins C and E, and additionally, it is known to exhibit a plethora of pharmacological effects. The present review summarizes the protective molecular mechanisms of actions of astaxanthin on age-related diseases of multiple organs such as Neurodegenerative diseases [Alzheimer's disease (AD), Parkinson's disease (PD), Stroke, Multiple Sclerosis (MS), Amyotrophic lateral sclerosis (ALS), and Status Epilepticus (SE)], Bone Related Diseases [Osteoarthritis (OA) and Osteoporosis], Cancers [Colon cancer, Prostate cancer, Breast cancer, and Lung Cancer], Cardiovascular disorders [Hypertension, Atherosclerosis and Myocardial infarction (MI)], Diabetes associated complications [Diabetic nephropathy (DN), Diabetic neuropathy, and Diabetic retinopathy (DR)], Eye disorders [Age related macular degeneration (AMD), Dry eye disease (DED), Cataract and Uveitis], Gastric Disorders [Gastritis, Colitis, and Functional dyspepsia], Kidney Disorders [Nephrolithiasis, Renal fibrosis, Renal Ischemia reperfusion (RIR), Acute kidney injury (AKI), and hyperuricemia], Liver Diseases [Nonalcoholic fatty liver disease (NAFLD), Alcoholic Liver Disease (AFLD), Liver fibrosis, and Hepatic Ischemia-Reperfusion (IR) Injury], Pulmonary Disorders [Pulmonary Fibrosis, Acute Lung injury (ALI), and Chronic obstructive pulmonary disease (COPD)], Muscle disorders (skeletal muscle atrophy), Skin diseases [Atopic dermatitis (ATD), Skin Photoaging, and Wound healing]. We have also briefly discussed astaxanthin's protective effects on reproductive health.
Asunto(s)
Antioxidantes , Calidad de Vida , Masculino , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Envejecimiento , Carotenoides , Isquemia/tratamiento farmacológicoRESUMEN
Globally, millions of people suffer from poor wound healing, which is associated with higher mortality rates and higher healthcare costs. There are several factors that can complicate the healing process of wounds, including inadequate conditions for cell migration, proliferation, and angiogenesis, microbial infections, and prolonged inflammatory responses. Current therapeutic methods have not yet been able to resolve several primary problems; therefore, their effectiveness is limited. As a result of their remarkable properties, bio-based materials have been demonstrated to have a significant impact on wound healing in recent years. In the wound microenvironment, bio-based materials can stimulate numerous cellular and molecular processes that may enhance healing by inhibiting the growth of pathogens, preventing inflammation, and stimulating angiogenesis, potentially converting a non-healing environment to an appropriately healing one. The aim of this present review article is to provide an overview of the mechanisms underlying wound healing and its pathophysiology. The development of bio-based nanomaterials for chronic diabetic wounds as well as novel methodologies for stimulating wound healing mechanisms are also discussed.
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Diabetes Mellitus , Nanoestructuras , Humanos , Diabetes Mellitus/terapia , Cicatrización de Heridas , Movimiento Celular , InflamaciónRESUMEN
The yeast Saccharomyces cerevisiae PEP4 gene encodes vacuolar endopeptidase proteinase A (Pep4p), which is a homolog of the human CTSD gene that encodes cathepsin D. Mutation of CTSD gene in human resulted in a number of neurodegenerative diseases. In this study, we have shown that yeast pep4 mutant cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen peroxide and acetic acid, respectively. pep4∆ cells also showed accumulation of reactive oxygen species (ROS), apoptotic markers, and reduced chronological lifespan. In contrast, quercetin pretreatment protected the pep4 mutant from oxidative and apoptotic stress-induced sensitivity by scavenging ROS and reducing apoptotic markers. The percentage viability of quercetin-treated pep4∆ cells was more pronounced and increased stress resistance against oxidant, apoptotic, and heat stress during chronological aging. From our experimental results, we concluded that quercetin protects yeast pep4 mutant cells from oxidative stress and apoptosis, thereby increasing viability during chronological aging.
Asunto(s)
Apoptosis/efectos de los fármacos , Ácido Aspártico Endopeptidasas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Quercetina/farmacología , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/enzimología , Ácido Acético/farmacología , Ácido Aspártico Endopeptidasas/genética , Peróxido de Hidrógeno/farmacología , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genéticaRESUMEN
The Saccharomyces cerevisiae TEL1 gene is an ortholog of the human ATM (Ataxia telangiectasia mutated) gene. S. cerevisiae tel1 mutant (tel1∆) lacking Tel1p, share some of the cellular defects with ATM mutation that includes prevention of oxidative damage repair, premature aging and apoptosis. In the present study, we investigated the protective effects of quercetin on the sensitivity of yeast S. cerevisiae tel1∆ cells exposed to oxidative, apoptotic and DNA damaging stress and viability of tel1∆ cells during chronological aging. Quercetin improved the stress resistance of tel1∆ cells when challenged with oxidants such as hydrogen peroxide (H2O2), menadine bisulphite (MBS) and tertiary butyl hydroperoxide (t-BHP) by scavenging reactive oxygen species (ROS). Quercetin protected the tel1∆ cells from acetic acid-induced apoptotic cell death and sensitivity against hydroxyurea. We found that quercetin attenuated ROS accumulation and apoptotic markers in tel1∆ cells and therefore an increase in cell viability during chronological aging. Our results from the S. cerevisiae model, suggest that use of quercetin as a food supplement might alleviate oxidative stress mediated DNA damage, apoptosis and age related damaging effects in AT patients and also improve health beneficial effects in humans.
RESUMEN
Levan is a fructose-based biopolymer with diverse applications in the medicinal, pharmaceutical, and food industries. However, despite its extensive biological and pharmacological actions, including antioxidant, anti-inflammatory, and antidiabetic properties, research on its anti-aging potential is limited. This study explored levan's impact on the chronological lifespan (CLS) of yeast Saccharomyces cerevisiae for the first time. The results show that levan treatment significantly extended the CLS of wild-type (WT) yeast by preventing the accumulation of oxidative stress markers (reactive oxygen species, malondialdehyde, and protein carbonyl content) and ameliorating apoptotic features such as reduced mitochondrial membrane potential, loss of plasma membrane integrity, and externalization of phosphatidylserine. By day 40 of the CLS, a significant increase in yeast viability of 6.8 % (p < 0.01), 11.9 % (p < 0.01), and 20.8 % (p < 0.01) was observed at 0.25, 0.5, and 1 mg/mL of levan concentrations, respectively, compared to control (0 %). This study's results indicate that levan treatment substantially modulates the expression of genes involved in the TORC1/Sch9 pathway. Moreover, levan treatment significantly extended the CLS of yeast antioxidant-deficient mutant sod2Δ and antiapoptotic gene-deficient mutant pep4Δ. Levan also extended the CLS of signaling pathway gene-deficient mutants such as pkh2Δ, rim15Δ, atg1, and ras2Δ, while not affecting the CLS of tor1Δ and sch9Δ.
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Fructanos , Estrés Oxidativo , Saccharomyces cerevisiae , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Fructanos/farmacología , Estrés Oxidativo/efectos de los fármacos , Antioxidantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Apoptosis/efectos de los fármacos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacosRESUMEN
Background: A significant area of clinical research is the development of natural wound healing products and the management of chronic wounds. Healing wounds with medicinal plants has been a practice of ancient civilizations for centuries. Nigella sativa L ( N. sativa) is a medicinal plant that has several pharmacological properties. Methods: The present study evaluated the wound healing properties of Nigella sativa L. ( N. sativa) seed extracts using normal cell lines such as normal human dermal fibroblasts (NHDFs) and human umbilical vein endothelial cells (HUVECs). The expression levels of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) were analyzed through western blot analysis. Furthermore, computational analyses were carried out to screen the potential bioactive compounds for wound healing applications. Results: The results of the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay revealed that, all the tested solvent extracts of N. sativa seeds (including ethanol, ethyl acetate, chloroform, and petroleum ether) did not exert any cytotoxic effects at the tested concentrations. Furthermore, the western blot analysis showed elevated levels of VEGF and PDGF upon treatment with N. sativa seed extracts. Gas chromatography-mass spectrometry (GC-MS) analysis of N. sativa extracts identified 268 phytocompounds. Molecular docking studies revealed that three phytocompounds of N. sativa extracts, including tricyclo[20.8.0.0(7,16)]triacontane, 1(22),7(16)-diepoxy-, adaphostin and obeticholic acid had strong binding affinity with wound healing-related target proteins, showing docking scores ranging from -5.5 to -10.9 Kcal/mol. These compounds had acceptable Absorption, Distribution, Metabolism, and Excretion (ADME) properties. Conclusions: Based on these results, N. sativa seed extracts might possess potential wound healing properties owing to the presence of a wide range of bioactive components.
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Nigella sativa , Humanos , Nigella sativa/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Factor A de Crecimiento Endotelial Vascular , Factor de Crecimiento Derivado de Plaquetas , Células Endoteliales , Simulación del Acoplamiento Molecular , Cicatrización de Heridas , Transducción de SeñalRESUMEN
Neurodegenerative diseases are characterized by the progressive loss of neurons and intricate interactions between different cell types within the affected regions. Reliable biomarkers that can accurately reflect disease activity, diagnose, and monitor the progression of neurodegenerative diseases are crucial for the development of effective therapies. However, identifying suitable biomarkers has been challenging due to the heterogeneous nature of these diseases, affecting specific subsets of neurons in different brain regions. One promising approach for promoting brain regeneration and recovery involves the transplantation of mesenchymal stem cells (MSCs). MSCs have demonstrated the ability to modulate the immune system, promote neurite outgrowth, stimulate angiogenesis, and repair damaged tissues, partially through the release of their extracellular vesicles (EVs). MSC-derived EVs retain some of the therapeutic characteristics of their parent MSCs, including their ability to regulate neurite outgrowth, promote angiogenesis, and facilitate tissue repair. This review aims to explore the potential of MSC-derived EVs as an emerging therapeutic strategy for neurodegenerative diseases, highlighting their role in modulating disease progression and promoting neuronal recovery. By elucidating the mechanisms by which MSC-derived EVs exert their therapeutic effects, we can advance our understanding and leverage their potential for the development of novel treatment approaches in the field of neurodegenerative diseases.
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Vesículas Extracelulares , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas , Enfermedades Neurodegenerativas , Humanos , Enfermedades Neurodegenerativas/terapia , Enfermedades Neurodegenerativas/metabolismo , Vesículas Extracelulares/metabolismo , Encéfalo , Células Madre Mesenquimatosas/metabolismoRESUMEN
Understanding the basis of biological diversity remains a central problem in evolutionary biology. Using microbial systems, adaptive diversification has been studied in (a) spatially heterogeneous environments, (b) temporally segregated resources, and (c) resource specialization in a homogeneous environment. However, it is not well understood how adaptive diversification can take place in a homogeneous environment containing a single resource. Starting from an isogenic population of yeast Saccharomyces cerevisiae, we report rapid adaptive diversification, when propagated in an environment containing melibiose as the carbon source. The diversification is driven due to a public good enzyme α-galactosidase, which hydrolyzes melibiose into glucose and galactose. The diversification is driven by mutations at a single locus, in the GAL3 gene in the S. cerevisiae GAL/MEL regulon. We show that metabolic co-operation involving public resources could be an important mode of generating biological diversity. Our study demonstrates sympatric diversification of yeast starting from an isogenic population and provides detailed mechanistic insights into the factors and conditions responsible for generating and maintaining the population diversity.
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Melibiosa , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genética , Melibiosa/metabolismo , Galactosa/metabolismo , Genotipo , alfa-Galactosidasa/genética , alfa-Galactosidasa/metabolismoRESUMEN
Cellular homeostasis maintained by several cellular processes such as autophagy, apoptosis, inflammation, oxidative stress, aging, and neurodegeneration, contribute to cell growth and development. Cancer cells undergo aberrant changes from a normal cell that show abnormal behaviour such as reduced apoptosis and autophagy, increased oxidative stress and inflammation. Various pharmacological and genetic inhibitors have been reported as drug candidates to control cancer cells, but the use of natural molecules as anti-cancer agents are limited. There is an emerging need for the development of alternative natural therapeutic agents that maintain cellular homeostasis without affecting cell viability and physiology. This review highlights the multifunctional roles of Trehalose, a natural disaccharide that can target various cellular processes in the cancer. Trehalose possessing an antioxidant activity also has effect on cancer, which is explained through targeting cell progression, angiogenesis and metastasis pathways at molecular level targeting EGFR, PI3K, Akt, VEGF and MMP 9 proteins inside the cell.
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Neoplasias/metabolismo , Trehalosa/metabolismo , Animales , Apoptosis , Autofagia , Humanos , Neoplasias/patología , Estrés Oxidativo , Transducción de SeñalRESUMEN
Oxidative stress-mediated neurodegeneration is responsible for 12% mortality around the globe. Alzheimer's Disease (AD) and Parkinson's Disease (PD) are the most prevalent neurodegenerative diseases, associated with modulation of acetylcholine levels and amyloid beta accumulation & dopamine level and alpha-synuclein oligomerization, respectively. Therefore, a better understanding of their pathological mechanisms reveals novel target proteins and encourages exploitation of suitable lead molecules. In the present study, targets for AD and PD were sought not only to suppress the pathological condition but to restore the normal physiological function. In this view, activation of retinoic acid receptor alpha can be formulated as a novel target to improve choline acetyltransferase transcription that works together with acetylcholine esterase and beta-secretase 1 inhibition against AD. Likewise, inhibition of Polo-like kinase 2 fails to phosphorylate alpha-synuclein and motivates efficient autophagic clearance. Therefore, PLK2 inhibition, together with L-DOPA supplementation and monoamine oxidase B inhibition widens the therapeutic options for PD. As oxidative stress is the major factor for neurodegeneration, AMPK activation stabilizes energy metabolism and Sirtuin 1 (histone deacetylase 1) activation enhances AMPK, PGC1a and Nrf gene expressions. Phytochemical extracts from saffron stigma were broadly appreciated on memory enhancement and cognition. However, the exact mechanism was not established. Therefore, this inspires the exploitation of phytochemicals in saffron stigma extract using in-silico tools, to anticipate lead molecules that interact with various neurodegeneration associated protein targets.
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Enfermedad de Alzheimer , Crocus , Enfermedad de Parkinson , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Crocus/metabolismo , Humanos , Estrés OxidativoRESUMEN
BACKGROUND AND AIM: Aging is associated with oxidative stress and altered cholinergic and mitochondrial function. Crocin is a carotenoid antioxidant that quenches free radicals and protects cells and tissues from oxidation in biological systems. The aim of the present study is to investigate the effect of oral supplementation of Crocin on age-associated oxidative stress, cholinergic, and mitochondrial function in rat cerebral cortex. MAIN METHODS: The middle-aged (15 months old) rats were segregated into three groups (n = 6): Control (ad-libitum fed +0.9% saline as vehicle), Cro 50 (ad-libitum fed + crocin 50 mg/kg/day), Cro 150 (ad-libitum fed + crocin 150 mg/kg/day). The experiment was scheduled for 45 days. The serum and brain parameters were estimated after euthanasia. KEY FINDINGS: Crocin supplementation of Cro 50 and Cro 150 displayed a relative decline in body weight gain during the experimental period and significantly reduced age-associated serum triglyceride level over control. In rat cerebral cortex, age-associated macromolecular damage, decline in endogenous antioxidants and an increase in intracellular calcium concentration were significantly reversed due to oral supplementation of Crocin. Cro 150 significantly improved acetylcholine content as a consequence of acetylcholinesterase inhibition. Further, remarkable mitochondrial function was observed in Cro 150 over the control group as determined by citrate synthase and cytochrome C oxidase enzyme activities. SIGNIFICANCE: Oral supplementation of Crocin significantly reversed age-associated oxidative stress and neuroinflammatory markers. Meanwhile, Cro 150 remarkably improved cholinergic and mitochondrial function over the control group and facilitated further delay in the aging process due to enhanced cognitive effect.
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Envejecimiento/efectos de los fármacos , Biomarcadores/metabolismo , Carotenoides/farmacología , Corteza Cerebral/efectos de los fármacos , Colinérgicos/farmacología , Enfermedades Mitocondriales/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Acetilcolina/metabolismo , Acetilcolinesterasa/química , Administración Oral , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Carotenoides/administración & dosificación , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Colinérgicos/administración & dosificación , Inhibidores de la Colinesterasa/administración & dosificación , Inhibidores de la Colinesterasa/farmacología , Suplementos Dietéticos , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/patología , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patología , Ratas , Ratas WistarRESUMEN
We investigated the protective effect of a natural polyphenol, magnolol, on Saccharomyces cerevisiae cells under oxidative stress, and during aging. Our results showed the sensitivity of S. cerevisiae antioxidant gene deficient mutants (sod1∆, sod2∆, cta1∆, ctt1∆, gtt2∆ and tsa1∆) against hydrogen peroxide (H2O2) and menadione stress was rescued by magnolol as demonstrated in spot and colony forming unit counts. Yeast cells pretreated with magnolol showed decreased intracellular oxidation, lipid peroxidation and an increased level of reduced glutathione. Further, SOD1, CTA1 and GTT2 gene expression was examined by reverse transcription-polymerase chain reaction, and was found that magnolol significantly attenuated the upregulation of SOD1 and CTA1 genes under oxidative stress. Finally, longevity of the wild type and sod1 mutant cells were extended by magnolol, and also enhance stress resistance against oxidant stress during chronological aging.
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Antioxidantes/farmacología , Compuestos de Bifenilo/farmacología , Lignanos/farmacología , Estrés Oxidativo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Catalasa/genética , Recuento de Colonia Microbiana , Expresión Génica/efectos de los fármacos , Transportador de Glucosa de Tipo 2/genética , Glutatión/genética , Peroxidación de Lípido , Viabilidad Microbiana/efectos de los fármacos , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Superóxido Dismutasa-1/genéticaRESUMEN
Aging brain is characterized by a change in biomolecular composition leading to a diverse range of neurological diseases. Anti-aging research is of current interest, to lessen the burden of age-related macromolecular damage through antioxidant supplementation and caloric restriction. However, data concerning the effect of these anti-aging regimens on age-related biomolecular changes in rat brain is still lacking. In the present study, for the first time, we employed Fourier transform infrared (FTIR) spectroscopy, to investigate the effect of quercetin, caloric restriction (CR) and combination of both on alterations in the composition of lipids and proteins of aged rat brain cerebral cortex. Aged male Wistar rats (21â¯months old) were divided into four groups: Control (CONT), fed pellet diet; Quercetin (QUER), fed quercetin (50â¯mg/kg/day); CR (caloric restriction) (fed 40% reduced CONT), and CRQ (40% CR and 50â¯mg/kg/day QUER). Three-month-old rats served as young control (YOUNG). Our short-term study (45â¯days) shows decreased band area of unsaturated lipids, decreased area ratios of olefinic/lipid and CH2 antisymmetric stretching (2925â¯cm-1)/lipids in CONT group compared to young rats, suggesting age-associated lipid peroxidation in aged rats. A slight decrease in the frequency of CH2 antisymmetric mode of lipids (whereas no change in CH2 symmetric mode), but a decrease in bandwidths of both CH2 antisymmetric and symmetric modes of lipids was observed for CONT group compared to YOUNG. Further, a significant decrease in the peak area of infrared bands of proteins and an increase in the peak area of the CO band of lipids was observed in the CONT group. Our data also show that lower levels of α-helical structures and higher levels of random coils, representing altered protein secondary structure composition in the CONT group compared to YOUNG group. Reduction in neuronal cell density and shrinked nucleus was also observed in aged rats. Increase in the accumulation of oxidative mediated damage to macromolecules and diminished antioxidant levels, could be the possible reason for the age-related alterations in the composition of lipids and proteins. However, the combination of quercetin and CR, but not either treatment alone, significantly prevented the age associated alterations in the lipid and protein profiles in the rat cerebral cortex. Further, our results help to understand the mechanism of action of antioxidants under non-restriction and CR conditions, this might help in the development of novel anti-aging treatments to ameliorate oxidative stress in age-related disorders.
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Envejecimiento/efectos de los fármacos , Restricción Calórica , Corteza Cerebral/química , Lípidos/química , Quercetina/farmacología , Envejecimiento/fisiología , Amidas/química , Animales , Recuento de Células , Corteza Cerebral/efectos de los fármacos , Suplementos Dietéticos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Neuronas/citología , Neuronas/efectos de los fármacos , Proteínas/química , Ratas Wistar , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
BACKGROUND & OBJECTIVE: Aging is characterized by gradual accumulation of macromolecular damage leading to progressive loss of physiological function and increased susceptibility to diverse diseases. Effective anti-aging strategies involving caloric restriction or antioxidant supplementation are receiving growing attention to attenuate macromolecular damage in age associated pathology. METHOD: In the present study, we for the first time investigated the effect of quercetin, caloric restriction and combined treatment (caloric restriction with quercetin) on oxidative stress parameters, acetylcholinesterase and ATPases enzyme activities in the cerebral cortex of aged male Wistar rats. 21 months aged rats were divided into four groups (n=6-8) such as group 1-fed ad libitum (AL); group 2-quercetin supplementation of 50 mg/kg b.w/day for 45 days fed ad libitum (QUER); group 3: caloric restricted (CR) (fed 40% reduced AL for 45 days); group 4-fed 40% CR and 50 mg/kg b.w/day QUER for 45 days (CR + QUER). Group 5-three month age old rats served as young control (YOUNG). RESULTS: Our results demonstrate that combined treatment of caloric restriction and quercetin significantly improved the age associated decline in the activities of endogenous antioxidant enzymes [such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and glutathione (GSH) content and attenuated elevated levels of protein carbonyl content (PCC), lipid peroxidation, lipofuscin, reactive oxygen species (ROS), and nitric oxide (NO). Furthermore, it is also observed that combined treatment ameliorated age associated alterations in acetylcholine esterase (AChE) and adenosine triphosphatases (ATPases) such as Na+/K+-ATPase and Ca+2-ATPase (but not Mg+2- ATPase) enzyme activities. CONCLUSION: Finally, we conclude that combined treatment of caloric restriction and quercetin (but not either treatment alone) in late life is an effective anti-aging therapy to counteract the age related accumulation of oxidative macromolecular damage.