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Swer PB, Kharbuli B, Syiem D, Sharma R. Age-related decline in the expression of BRG1, ATM and ATR are partially reversed by dietary restriction in the livers of female mice. Biogerontology 2024; 25:1025-1037. [PMID: 38970714 DOI: 10.1007/s10522-024-10117-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 06/26/2024] [Indexed: 07/08/2024]
Abstract
BRG1 (Brahma-related gene 1) is a member of the SWI/SNF (switch/sucrose nonfermentable) chromatin remodeling complex which utilizes the energy from ATP hydrolysis for its activity. In addition to its role of regulating the expression of a vast array of genes, BRG1 mediates DNA repair upon genotoxic stress and regulates senescence. During organismal ageing, there is accumulation of unrepaired/unrepairable DNA damage due to progressive breakdown of the DNA repair machinery. The present study investigates the expression level of BRG1 as a function of age in the liver of 5- and 21-month-old female mice. It also explores the impact of dietary restriction on BRG1 expression in the old (21-month) mice. Salient findings of the study are: Real-time PCR and Western blot analyses reveal that BRG1 levels are higher in 5-month-old mice but decrease significantly with age. Dietary restriction increases BRG1 expression in the 21-month-old mice, nearly restoring it to the level observed in the younger group. Similar expression patterns are observed for DNA damage response genes ATM (Ataxia Telangiectasia Mutated) and ATR (Ataxia Telangiectasia and Rad3-related) with the advancement in age and which appears to be modulated by dietary restriction. BRG1 transcriptionally regulates ATM as a function of age and dietary restriction. These results suggest that BRG1, ATM and ATR are downregulated as mice age, and dietary restriction can restore their expression. This implies that dietary restriction may play a crucial role in regulating BRG1 and related gene expression, potentially maintaining liver repair and metabolic processes as mice age.
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Affiliation(s)
- Pynskhem Bok Swer
- Department of Biochemistry, North-Eastern Hill University, Shillong, 793022, India
| | | | - Donkupar Syiem
- Department of Biochemistry, North-Eastern Hill University, Shillong, 793022, India
| | - Ramesh Sharma
- Department of Biochemistry, North-Eastern Hill University, Shillong, 793022, India.
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Jamerson LE, Bradshaw PC. The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity. Antioxidants (Basel) 2024; 13:820. [PMID: 39061889 PMCID: PMC11273496 DOI: 10.3390/antiox13070820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Revised: 07/01/2024] [Accepted: 07/03/2024] [Indexed: 07/28/2024] Open
Abstract
Dietary restriction (DR) protocols frequently employ intermittent fasting. Following a period of fasting, meal consumption increases lipogenic gene expression, including that of NADPH-generating enzymes that fuel lipogenesis in white adipose tissue (WAT) through the induction of transcriptional regulators SREBP-1c and CHREBP. SREBP-1c knockout mice, unlike controls, did not show an extended lifespan on the DR diet. WAT cytoplasmic NADPH is generated by both malic enzyme 1 (ME1) and the pentose phosphate pathway (PPP), while liver cytoplasmic NADPH is primarily synthesized by folate cycle enzymes provided one-carbon units through serine catabolism. During the daily fasting period of the DR diet, fatty acids are released from WAT and are transported to peripheral tissues, where they are used for beta-oxidation and for phospholipid and lipid droplet synthesis, where monounsaturated fatty acids (MUFAs) may activate Nrf1 and inhibit ferroptosis to promote longevity. Decreased WAT NADPH from PPP gene knockout stimulated the browning of WAT and protected from a high-fat diet, while high levels of NADPH-generating enzymes in WAT and macrophages are linked to obesity. But oscillations in WAT [NADPH]/[NADP+] from feeding and fasting cycles may play an important role in maintaining metabolic plasticity to drive longevity. Studies measuring the WAT malate/pyruvate as a proxy for the cytoplasmic [NADPH]/[NADP+], as well as studies using fluorescent biosensors expressed in the WAT of animal models to monitor the changes in cytoplasmic [NADPH]/[NADP+], are needed during ad libitum and DR diets to determine the changes that are associated with longevity.
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Affiliation(s)
| | - Patrick C. Bradshaw
- Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, TN 37614, USA
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3
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Le NT. Metabolic regulation of endothelial senescence. Front Cardiovasc Med 2023; 10:1232681. [PMID: 37649668 PMCID: PMC10464912 DOI: 10.3389/fcvm.2023.1232681] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 07/18/2023] [Indexed: 09/01/2023] Open
Abstract
Endothelial cell (EC) senescence is increasingly recognized as a significant contributor to the development of vascular dysfunction and age-related disorders and diseases, including cancer and cardiovascular diseases (CVD). The regulation of cellular senescence is known to be influenced by cellular metabolism. While extensive research has been conducted on the metabolic regulation of senescence in other cells such as cancer cells and fibroblasts, our understanding of the metabolic regulation of EC senescence remains limited. The specific metabolic changes that drive EC senescence are yet to be fully elucidated. The objective of this review is to provide an overview of the intricate interplay between cellular metabolism and senescence, with a particular emphasis on recent advancements in understanding the metabolic changes preceding cellular senescence. I will summarize the current knowledge on the metabolic regulation of EC senescence, aiming to offer insights into the underlying mechanisms and future research directions.
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Affiliation(s)
- Nhat-Tu Le
- Center for Cardiovascular Regeneration, Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX, United States
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Acevedo A, Torres F, Kiwi M, Baeza-Lehnert F, Barros LF, Lee-Liu D, González-Billault C. Metabolic switch in the aging astrocyte supported via integrative approach comprising network and transcriptome analyses. Aging (Albany NY) 2023; 15:9896-9912. [PMID: 37074814 PMCID: PMC10599759 DOI: 10.18632/aging.204663] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Accepted: 03/20/2023] [Indexed: 04/20/2023]
Abstract
Dysregulated central-energy metabolism is a hallmark of brain aging. Supplying enough energy for neurotransmission relies on the neuron-astrocyte metabolic network. To identify genes contributing to age-associated brain functional decline, we formulated an approach to analyze the metabolic network by integrating flux, network structure and transcriptomic databases of neurotransmission and aging. Our findings support that during brain aging: (1) The astrocyte undergoes a metabolic switch from aerobic glycolysis to oxidative phosphorylation, decreasing lactate supply to the neuron, while the neuron suffers intrinsic energetic deficit by downregulation of Krebs cycle genes, including mdh1 and mdh2 (Malate-Aspartate Shuttle); (2) Branched-chain amino acid degradation genes were downregulated, identifying dld as a central regulator; (3) Ketone body synthesis increases in the neuron, while the astrocyte increases their utilization, in line with neuronal energy deficit in favor of astrocytes. We identified candidates for preclinical studies targeting energy metabolism to prevent age-associated cognitive decline.
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Affiliation(s)
- Alejandro Acevedo
- Instituto de Nutrición y Tecnología de Alimentos (INTA), Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile
| | - Felipe Torres
- Department of Physics, Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile
- Center for the Development of Nanoscience and Nanotechnology, CEDENNA, Santiago, Región Metropolitana 7800003, Chile
- Department of Physics, Center for Advanced Nanoscience, University of California, San Diego, CA 92093, USA
| | - Miguel Kiwi
- Department of Physics, Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile
- Center for the Development of Nanoscience and Nanotechnology, CEDENNA, Santiago, Región Metropolitana 7800003, Chile
| | | | - L. Felipe Barros
- Centro de Estudios Científicos (CECs), Valdivia 5110466, Chile
- Facultad de Medicina y Ciencia, Universidad San Sebastián, Valdivia, Región de Los Ríos 5110773, Chile
| | - Dasfne Lee-Liu
- Department of Biology, Laboratory of Cellular and Neuronal Dynamics, Faculty of Sciences, Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile
- Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Región Metropolitana 7800003, Chile
- Facultad de Medicina y Ciencia, Universidad San Sebastián, Santiago, Región Metropolitana 7510157, Chile
| | - Christian González-Billault
- Department of Biology, Laboratory of Cellular and Neuronal Dynamics, Faculty of Sciences, Universidad de Chile, Santiago, Región Metropolitana 7800003, Chile
- Geroscience Center for Brain Health and Metabolism (GERO), Santiago, Región Metropolitana 7800003, Chile
- The Buck Institute for Research on Aging, Novato, CA 94945, USA
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Andrianova NV, Buyan MI, Bolikhova AK, Zorov DB, Plotnikov EY. Dietary Restriction for Kidney Protection: Decline in Nephroprotective Mechanisms During Aging. Front Physiol 2021; 12:699490. [PMID: 34295266 PMCID: PMC8291992 DOI: 10.3389/fphys.2021.699490] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Accepted: 06/10/2021] [Indexed: 01/07/2023] Open
Abstract
Dietary restriction (DR) is believed to be one of the most promising approaches to extend life span of different animal species and to delay deleterious age-related physiological alterations and diseases. Among others, DR was shown to ameliorate acute kidney injury (AKI) and chronic kidney disease (CKD). However, to date, a comprehensive analysis of the mechanisms of the protective effect of DR specifically in kidney pathologies has not been carried out. The protective properties of DR are mediated by a range of signaling pathways associated with adaptation to reduced nutrient intake. The adaptation is accompanied by a number of metabolic changes, such as autophagy activation, metabolic shifts toward lipid utilization and ketone bodies production, improvement of mitochondria functioning, and decreased oxidative stress. However, some studies indicated that with age, the gain of DR-mediated positive remodeling gradually decreases. This may be an obstacle if we seek to translate the DR approach into a clinic for the treatment of kidney diseases as most patients with AKI and CKD are elderly. It is well known that aging is accompanied by impairments in a huge variety of organs and systems, such as hormonal regulation, stress sensing, autophagy and proteasomal activity, gene expression, and epigenome profile, increased damage to macromolecules and organelles including mitochondria. All these age-associated changes might be the reasons for the reduced protective potential of the DR during aging. We summarized the available mechanisms of DR-mediated nephroprotection and described ways to improve the effectiveness of this approach for an aged kidney.
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Affiliation(s)
- Nadezda V Andrianova
- A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.,Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia
| | - Marina I Buyan
- Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia
| | - Anastasia K Bolikhova
- Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, Russia
| | - Dmitry B Zorov
- A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.,V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia
| | - Egor Y Plotnikov
- A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia.,V.I. Kulakov National Medical Research Center of Obstetrics, Gynecology and Perinatology, Moscow, Russia
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Mehdi MM, Solanki P, Singh P. Oxidative stress, antioxidants, hormesis and calorie restriction: The current perspective in the biology of aging. Arch Gerontol Geriatr 2021; 95:104413. [PMID: 33845417 DOI: 10.1016/j.archger.2021.104413] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Revised: 02/25/2021] [Accepted: 03/30/2021] [Indexed: 12/12/2022]
Abstract
Aging, in a large measure, has long been defined as the resultant of oxidative stress acting on the cells. The cellular machinery eventually malfunctions at the basic level by the damage from the processes of oxidation and the system starts slowing down because of intrinsic eroding. To understand the initial destruction at the cellular level spreading outward to affect tissues, organs and the organism, the relationship between molecular damage and oxidative stress is required to understand. Retarding the aging process is a matter of cumulatively decreasing the rate of oxidative damage to the cellular machinery. Along with the genetic reasons, the decrease of oxidative stress is somehow a matter of lifestyle and importantly of diet. In the current review, the theories of aging and the understanding of various levels of molecular damage by oxidative stress have been emphasized. A broader understanding of mechanisms of aging have been elaborated in terms of effects of oxidative at molecular, mitochondrial, cellular and organ levels. The antioxidants supplementation, hormesis and calorie restriction as the prominent anti-aging strategies have also been discussed. The relevance and the efficacy of the antiaging strategies at system level have also been presented.
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Affiliation(s)
- Mohammad Murtaza Mehdi
- Department of Biochemistry, School of Bio-engineering and Biosciences, Lovely Professional University, Phagwara, 144411, Punjab, India.
| | - Preeti Solanki
- Multidisciplinary Research Unit, Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak, 124001, Haryana, India
| | - Prabhakar Singh
- Department of Biochemistry, Veer Bahadur Singh Purvanchal University, Jaunpur, 222003, Uttar Pradesh, India
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Nikhalashree S, George R, Shantha B, Lingam V, Vidya W, Panday M, Sulochana KN, Coral K. Detection of Proteins Associated with Extracellular Matrix Regulation in the Aqueous Humour of Patients with Primary Glaucoma. Curr Eye Res 2019; 44:1018-1025. [DOI: 10.1080/02713683.2019.1608261] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Sampath Nikhalashree
- R.S. Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO, Vision Research Foundation, Sankara Nethralaya, Chennai, India
- School of Chemical and Biotechnology, SASTRA Deemed-to-be University, Thanjavur, India
| | - Ronnie George
- Smt Jadhavbai Nathmal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India
| | - Balekudaru Shantha
- Smt Jadhavbai Nathmal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India
| | - Vijaya Lingam
- Smt Jadhavbai Nathmal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India
| | - Wadke Vidya
- Smt Jadhavbai Nathmal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India
| | - Manish Panday
- Smt Jadhavbai Nathmal Singhvee Glaucoma Services, Medical Research Foundation, Sankara Nethralaya, Chennai, India
| | | | - Karunakaran Coral
- R.S. Mehta Jain Department of Biochemistry and Cell Biology, KBIRVO, Vision Research Foundation, Sankara Nethralaya, Chennai, India
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Long-term dietary restriction up-regulates activity and expression of renal arginase II in aging mice. J Biosci 2018; 42:275-283. [PMID: 28569251 DOI: 10.1007/s12038-017-9683-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023]
Abstract
Arginase II is a mitochondrial enzyme that catalyses the hydrolysis of L-arginine into urea and ornithine. It is present in other extra-hepatic tissues that lack urea cycle. Therefore, it is plausible that arginase II has a physiological role other than urea cycle which includes polyamine, proline, glutamate synthesis and regulation of nitric oxide production. The high expression of arginase II in kidney, among extrahepatic tissues, might have an important role associated with kidney functions. The present study is aimed to determine the age-associated alteration in the activity and expression of arginase II in the kidney of mice of different ages. The effect of dietary restriction to modulate the agedependent changes of arginase II was also studied. Results showed that renal arginase II activity declines significantly with the progression of age (p less than 0.01 and p less than 0.001 in 6- and 18-month-old mice, respectively as compared to 2-month old mice) and is due to the reduction in its protein as well as the mRNA level (p less than 0.001 in both 6- and 18-month-old mice as compared to 2-month-old mice). Long-term dietary restriction for three months has significantly up-regulated arginase II activity and expression level in both 2- and 18-month-old mice (p less than 0.01 and p less than 0.001, respectively as compared to AL group). These findings clearly indicate that the reducing level of arginase II during aging might have an impact on the declining renal functions. This age-dependent down-regulation of arginase II in the kidney can be attenuated by dietary restriction which may help in the maintenance of such functions.
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9
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Schofield Z, Reed MAC, Newsome PN, Adams DH, Günther UL, Lalor PF. Changes in human hepatic metabolism in steatosis and cirrhosis. World J Gastroenterol 2017; 23:2685-2695. [PMID: 28487605 PMCID: PMC5403747 DOI: 10.3748/wjg.v23.i15.2685] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2016] [Revised: 01/11/2017] [Accepted: 03/15/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To understand the underlying metabolic changes in human liver disease we have applied nuclear magnetic resonance (NMR) metabolomics analysis to human liver tissue.
METHODS We have carried out pilot study using 1H-NMR to derive metabolomic signatures from human liver from patients with steatosis, nonalcoholic steatohepatitis (NASH) or alcohol-related liver damage (ARLD) to identify species that can predict outcome and discriminate between alcohol and metabolic-induced liver injuries.
RESULTS Changes in branched chain amino acid homeostasis, tricarboxylic acid cycle and purine biosynthesis intermediates along with betaine were associated with the development of cirrhosis in both ARLD and nonalcoholic fatty liver disease. Species such as propylene glycol and as yet unidentified moieties that allowed discrimination between NASH and ARLD samples were also detected using our approach.
CONCLUSION Our high throughput, non-destructive technique for multiple analyte quantification in human liver specimens has potential for identification of biomarkers with prognostic and diagnostic significance.
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Kim GY, Lee YM, Cho JH, Pan CJ, Jun HS, Springer DA, Mansfield BC, Chou JY. Mice expressing reduced levels of hepatic glucose-6-phosphatase-α activity do not develop age-related insulin resistance or obesity. Hum Mol Genet 2015; 24:5115-25. [PMID: 26089201 DOI: 10.1093/hmg/ddv230] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2015] [Accepted: 06/15/2015] [Indexed: 12/26/2022] Open
Abstract
Glycogen storage disease type-Ia (GSD-Ia) is caused by a lack of glucose-6-phosphatase-α (G6Pase-α or G6PC) activity. We have shown that gene therapy mediated by a recombinant adeno-associated virus (rAAV) vector expressing human G6Pase-α normalizes blood glucose homeostasis in the global G6pc knockout (G6pc(-/-)) mice for 70-90 weeks. The treated G6pc(-/-) mice expressing 3-63% of normal hepatic G6Pase-α activity (AAV mice) produce endogenous hepatic glucose levels 61-68% of wild-type littermates, have a leaner phenotype and exhibit fasting blood insulin levels more typical of young adult mice. We now show that unlike wild-type mice, the lean AAV mice have increased caloric intake and do not develop age-related obesity or insulin resistance. Pathway analysis shows that signaling by hepatic carbohydrate response element binding protein that improves glucose tolerance and insulin signaling is activated in AAV mice. In addition, several longevity factors in the calorie restriction pathway, including the NADH shuttle systems, NAD(+) concentrations and the AMP-activated protein kinase/sirtuin 1/peroxisome proliferator-activated receptor-γ coactivator 1α pathway are upregulated in the livers of AAV mice. The finding that partial restoration of hepatic G6Pase-α activity in GSD-Ia mice not only attenuates the phenotype of hepatic G6Pase-α deficiency but also prevents the development of age-related obesity and insulin resistance seen in wild-type mice may suggest relevance of the G6Pase-α enzyme to obesity and diabetes.
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Affiliation(s)
- Goo-Young Kim
- Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and
| | - Young Mok Lee
- Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and
| | - Jun-Ho Cho
- Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and
| | - Chi-Jiunn Pan
- Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and
| | - Hyun Sik Jun
- Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and
| | - Danielle A Springer
- Mouse Phenotyping Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA and
| | - Brian C Mansfield
- Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and Foundation Fighting Blindness, Columbia, MD 21046, USA
| | - Janice Y Chou
- Section on Cellular Differentiation, Program on Developmental Endocrinology and Genetics, Eunice Kennedy Shriver National Institute of Child Health and Human Development and
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Age-dependent increased expression and activity of inorganic pyrophosphatase in the liver of male mice and its further enhancement with short- and long-term dietary restriction. Biogerontology 2013; 15:81-6. [PMID: 24271717 DOI: 10.1007/s10522-013-9481-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 11/09/2013] [Indexed: 02/07/2023]
Abstract
Intracellular orthophosphate and inorganic pyrophosphate (PPi) are by-products of multiple biosynthetic reactions. PPi hydrolysis by soluble inorganic pyrophosphatase (iPPase) has been considered as an important homeostatic mechanism. We investigated the expression and activities (U/mg protein) of iPPase in the liver of young and old mice subjected to short- and long-term dietary restriction. The expression level of iPPase was ascertained by the Western blot analysis using anti-iPPase and differential polymerase chain reaction using iPPase specific primer. Older mice showed a significant increase in the expression and activity of iPPase as compared to younger ones. Short-term fasting of 24 h increased the expression and activity of iPPase in the liver of both young and old mice which were reversed upon 24 h of re-feeding them. However, both young and old mice on long-term dietary restriction showed a cumulative increase in the expression and activity of iPPase when compared with their age-matched controls. This might be due to accumulative adaptation to refill energy deficiency of long-term dietary restricted mice for ATP generation via oxidative phosphorylation, where fatty acid activation could be driven by elevated iPPase.
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Late-onset dietary restriction compensates for age-related increase in oxidative stress and alterations of HSP 70 and synapsin 1 protein levels in male Wistar rats. Biogerontology 2009; 11:197-209. [PMID: 19609710 DOI: 10.1007/s10522-009-9240-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2009] [Accepted: 06/30/2009] [Indexed: 12/17/2022]
Abstract
Numerous reports implicate increased oxidative stress in the functional and structural changes occurring in the brain and other organs as a part of the normal aging process. Dietary restriction (DR) has long been shown to be life-prolonging intervention in several species. This study was aimed to assess the potential efficacy of late-onset short term DR when initiated in 21 months old male wistar rats for 3 months on the antioxidant defense system and lipid peroxidation, cellular stress response protein HSP 70 and synaptic marker protein synapsin 1 in discrete brain regions such as cortex, hypothalamus, and hippocampus as well as liver, kidney and heart from 24 month old rats. Age-associated decline in activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione, and elevated levels of lipid peroxidation was observed in brain and peripheral organ as well as increased expression of HSP 70 and reduction in synapsin 1 was observed in brain studied. Late-onset short term DR was effective in partially restoring the antioxidant status and in decreasing lipid peroxidation level as well as enhancing the expression of HSP 70 and synapsin 1 in aged rats. Late onset short term DR also prevented age-related neurodegeneration as revealed by Fluoro-Jade B staining in hippocampus and cortex regions of rat brain. Thus our current results suggest that DR initiated even in old age has the potential to improve age related decline in body functions.
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