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Lai C, Li R, Tang W, Liu J, Duan XDXF, Bao D, Liu H, Fu S. Metabolic Syndrome and Tendon Disease: A Comprehensive Review. Diabetes Metab Syndr Obes 2024; 17:1597-1609. [PMID: 38616994 PMCID: PMC11015851 DOI: 10.2147/dmso.s459060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 03/21/2024] [Indexed: 04/16/2024] Open
Abstract
Metabolic syndrome (MS) is a multifaceted pathological condition characterized by the atypical accumulation of various metabolic components such as central obesity or excess weight, hyperlipidemia, low-density lipoprotein (LDL), hypertension, and insulin resistance. Recently, MS has been recognized as a notable contributor to heart and circulatory diseases. In addition, with increasing research, the impact of MS on tendon repair and disease has gradually emerged. Recent studies have investigated the relationship between tendon healing and diseases such as diabetes, dyslipidemia, obesity, and other metabolic disorders. However, diabetes mellitus (DM), hypercholesterolemia, obesity, and various metabolic disorders often coexist and together constitute MS. At present, insulin resistance is considered the major pathological mechanism underlying MS, central obesity is regarded as the predominant factor responsible for it, and dyslipidemia and other metabolic diseases are known as secondary contributors to MS. This review aims to evaluate the current literature regarding the impact of various pathological conditions in MS on tendon recovery and illness, and to present a comprehensive overview of the effects of MS on tendon recovery and diseases, along with the accompanying molecular mechanisms.
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Affiliation(s)
- Canhao Lai
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Ruichen Li
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Weili Tang
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Jinyu Liu
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Xinfang D X F Duan
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Dingsu Bao
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
- Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Huan Liu
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
| | - Shijie Fu
- Department of Bone and Joint, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China
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Shi L, Lu PP, Dai GC, Li YJ, Rui YF. Advanced glycation end productions and tendon stem/progenitor cells in pathogenesis of diabetic tendinopathy. World J Stem Cells 2021; 13:1338-1348. [PMID: 34630866 PMCID: PMC8474716 DOI: 10.4252/wjsc.v13.i9.1338] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/26/2021] [Accepted: 08/17/2021] [Indexed: 02/06/2023] Open
Abstract
Tendinopathy is a challenging complication observed in patients with diabetes mellitus. Tendinopathy usually leads to chronic pain, limited joint motion, and even ruptured tendons. Imaging and histological analyses have revealed pathological changes in various tendons of patients with diabetes, including disorganized arrangement of collagen fibers, microtears, calcium nodules, and advanced glycation end product (AGE) deposition. Tendon-derived stem/ progenitor cells (TSPCs) were found to maintain hemostasis and to participate in the reversal of tendinopathy. We also discovered the aberrant osteochondrogenesis of TSPCs in vitro. However, the relationship between AGEs and TSPCs in diabetic tendinopathy and the underlying mechanism remain unclear. In this review, we summarize the current findings in this field and hypothesize that AGEs could alter the properties of tendons in patients with diabetes by regulating the proliferation and differentiation of TSPCs in vivo.
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Affiliation(s)
- Liu Shi
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Pan-Pan Lu
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Guang-Chun Dai
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ying-Juan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
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Tavares JF, Ribeiro PVM, Coelho OGL, Silva LED, Alfenas RCG. Can advanced glycation end-products and their receptors be affected by weight loss? A systematic review. Obes Rev 2020; 21:e13000. [PMID: 31950676 DOI: 10.1111/obr.13000] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 11/28/2019] [Accepted: 12/12/2019] [Indexed: 01/08/2023]
Abstract
Advanced glycation end products (AGEs) have been implicated in the pathogenesis of most chronic diseases. Therefore, identification of treatments that can attenuate the effects of these compounds and prevent cardiometabolic complications is of extreme public health interest. Recently, body weight management interventions showed positive results on reducing serum AGE concentrations. Moreover, the soluble receptor for advanced glycation end products (sRAGE) is considered to be a novel biomarker to identify patients with obesity most likely to benefit from weight management interventions. This systematic review aimed to critically analyze papers evaluating the effects of weight loss on serum AGEs and its receptors in adults with excess body weight. MEDLINE, Cochrane, Scopus, and Lilacs databases were searched. Three studies evaluating the response of AGEs to energy-restricted diets and six assessing sRAGE as the primary outcome were included. Energy-restricted diets and bariatric surgery reduced serum AGE concentrations, but effects on endogenous secretory RAGE (esRAGE) and sRAGE concentrations are conflicting. These results may be associated with mechanisms related to changes in dietary intake and limiting endogenous AGE formation. Therefore, the role of energy-restricted diets and bariatric surgery on lowering serum AGE concentrations, as well as its effects on AGEs receptors, deserves further investigation.
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Affiliation(s)
- Juliana F Tavares
- Departamento de Nutrição e Saúde, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | - Priscila V M Ribeiro
- Departamento de Nutrição e Saúde, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | - Olívia G L Coelho
- Departamento de Nutrição e Saúde, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | - Laís E da Silva
- Departamento de Nutrição e Saúde, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
| | - Rita C G Alfenas
- Departamento de Nutrição e Saúde, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
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Haefke A, Ewald C. Tail Tendon Break Time for the Assessment of Aging and Longitudinal Healthspan in Mice. Bio Protoc 2020. [DOI: 10.21769/bioprotoc.3833] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022] Open
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Dai GC, Li YJ, Chen MH, Lu PP, Rui YF. Tendon stem/progenitor cell ageing: Modulation and rejuvenation. World J Stem Cells 2019; 11:677-692. [PMID: 31616543 PMCID: PMC6789185 DOI: 10.4252/wjsc.v11.i9.677] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 08/15/2019] [Accepted: 09/05/2019] [Indexed: 02/06/2023] Open
Abstract
Tendon ageing is a complicated process caused by multifaceted pathways and ageing plays a critical role in the occurrence and severity of tendon injury. The role of tendon stem/progenitor cells (TSPCs) in tendon maintenance and regeneration has received increasing attention in recent years. The decreased capacity of TSPCs in seniors contributes to impaired tendon functions and raises questions as to what extent these cells either affect, or cause ageing, and whether these age-related cellular alterations are caused by intrinsic factors or the cellular environment. In this review, recent discoveries concerning the biological characteristics of TSPCs and age-related changes in TSPCs, including the effects of cellular epigenetic alterations and the mechanisms involved in the ageing process, are analyzed. During the ageing process, TSPCs ageing might occur as a natural part of the tendon ageing, but could also result from decreased levels of growth factor, hormone deficits and changes in other related factors. Here, we discuss methods that might induce the rejuvenation of TSPC functions that are impaired during ageing, including moderate exercise, cell extracellular matrix condition, growth factors and hormones; these methods aim to rejuvenate the features of youthfulness with the ultimate goal of improving human health during ageing.
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Affiliation(s)
- Guang-Chun Dai
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Ying-Juan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China
| | - Min-Hao Chen
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Pan-Pan Lu
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
| | - Yun-Feng Rui
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing210009, Jiangsu Province, China
- Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- Orthopaedic Trauma Institute, Southeast University, Nanjing 210009, Jiangsu Province, China
- School of Medicine, Southeast University, Nanjing 210009, Jiangsu Province, China
- China Orthopedic Regenerative Medicine Group, Hangzhou 310000, Zhejiang Province, China
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6
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Li Y, Dai G, Shi L, Lin Y, Chen M, Li G, Rui Y. The Potential Roles of Tendon Stem/Progenitor Cells in Tendon Aging. Curr Stem Cell Res Ther 2019; 14:34-42. [PMID: 30332976 DOI: 10.2174/1574888x13666181017112233] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 09/15/2018] [Accepted: 10/02/2018] [Indexed: 12/15/2022]
Abstract
Aging is a key dangerous factor for the occurrence and severity of tendon injury, but the exact cognition of the relationship is elusive at present. More previous studies suggest age-related changes occur at tendon mechanical properties, structure and composition, but the pathological alternations may be overlooked, which might be a cause for the structure and function variations, and even speed up the progress of age-related disorders. Recently, the presence of tendon stem/progenitor cells (TSPCs) would provide new insights for the pathogenesis of tendon aging. In this review, the tendon mechanical properties, structure and composition are presented in brief, then, the pathological changes of the aging tendon are described firstly, and the latest researches on alterations of TSPCs in the pathogenesis of tendon aging have also been analyzed. At a cellular level, the hypothetical model of altered TSPCs fate for tendon aging is also proposed. Moreover, the regulation of TSPCs as a potential way of the therapies for age-related tendon diseases is discussed. Therefore, reversing the impaired function of TSPCs and promoting the tenogenic differentiation of TSPCs could become hot spots for further study and give the opportunity to establish new treatment strategies for age-related tendon injuries.
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Affiliation(s)
- Yingjuan Li
- Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, 87 Ding Jia Qiao, Nanjing 210009, China.,School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China.,China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310000, China
| | - Guangchun Dai
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China.,Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China.,Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China.,Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Liu Shi
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China.,Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China.,Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China.,Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.,Program of Stem Cell and Regeneration, School of Biomedical Science, and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yucheng Lin
- Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China.,Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China.,Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Minhao Chen
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China.,Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China.,Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China.,Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
| | - Gang Li
- Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China.,Program of Stem Cell and Regeneration, School of Biomedical Science, and Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR, China
| | - Yunfeng Rui
- School of Medicine, Southeast University, N0.87 Ding Jia Qiao, Nanjing 210009, China.,China Orthopedic Regenerative Medicine Group, Hangzhou, Zhejiang 310000, China.,Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, NO.87 Ding Jia Qiao, Nanjing, Jiangsu 210009, China.,Orthopaedic Trauma Institute, Southeast University, Nanjing, Jiangsu 210009, China.,Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, No. 87 Ding Jia Qiao, Nanjing, Jiangsu, 210009, China
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7
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Eriksen CS, Svensson RB, Gylling AT, Couppé C, Magnusson SP, Kjaer M. Load magnitude affects patellar tendon mechanical properties but not collagen or collagen cross-linking after long-term strength training in older adults. BMC Geriatr 2019; 19:30. [PMID: 30704412 PMCID: PMC6357404 DOI: 10.1186/s12877-019-1043-0] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2018] [Accepted: 01/23/2019] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Regular loading of tendons may counteract the negative effects of aging. However, the influence of strength training loading magnitude on tendon mechanical properties and its relation to matrix collagen content and collagen cross-linking is sparsely described in older adults. The purpose of the present study was to compare the effects of moderate or high load resistance training on tendon matrix and its mechanical properties. METHODS Seventeen women and 19 men, age 62-70 years, were recruited and randomly allocated to 12 months of heavy load resistance training (HRT), moderate load resistance training (MRT) or control (CON). Pre- and post-intervention testing comprised isometric quadriceps strength test (IsoMVC), ultrasound based testing of in vivo patellar tendon (PT) mechanical properties, MRI-based measurement of PT cross-sectional area (CSA), PT biopsies for assessment of fibril morphology, collagen content, enzymatic cross-links, and tendon fluorescence as a measure of advanced glycation end-products (AGEs). RESULTS Thirty three participants completed the intervention and were included in the data analysis. IsoMVC increased more after HRT (+ 21%) than MRT (+ 8%) and CON (+ 7%) (p < 0.05). Tendon stiffness (p < 0.05) and Young's modulus (p = 0.05) were also differently affected by training load with a reduction in CON and MRT but not in HRT. PT-CSA increased equally after both MRT and HRT. Collagen content, fibril morphology, enzymatic cross-links, and tendon fluorescence were unaffected by training. CONCLUSION Despite equal improvements in tendon size after moderate and heavy load resistance training, only heavy. load training seemed to maintain tendon mechanical properties in old age. The effect of load magnitude on tendon biomechanics was unrelated to changes of major load bearing matrix components in the tendon core. The study is a sub-study of the LISA study, which was registered at http://clinicaltrials.gov (NCT02123641) April 25th 2014.
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Affiliation(s)
- Christian S Eriksen
- Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Nielsine Nielsens Vej 11, building 8, 1st floor, DK-2400, Copenhagen, Denmark. .,Center for Healthy Aging, Department of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, N, Denmark.
| | - Rene B Svensson
- Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Nielsine Nielsens Vej 11, building 8, 1st floor, DK-2400, Copenhagen, Denmark
| | - Anne T Gylling
- Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Nielsine Nielsens Vej 11, building 8, 1st floor, DK-2400, Copenhagen, Denmark.,Center for Healthy Aging, Department of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, N, Denmark
| | - Christian Couppé
- Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Nielsine Nielsens Vej 11, building 8, 1st floor, DK-2400, Copenhagen, Denmark.,Department of Physical and Occupational Therapy, Bispebjerg Hospital, Nielsine Nielsens Vej 11, DK-2400, Copenhagen, Denmark
| | - S Peter Magnusson
- Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Nielsine Nielsens Vej 11, building 8, 1st floor, DK-2400, Copenhagen, Denmark.,Department of Physical and Occupational Therapy, Bispebjerg Hospital, Nielsine Nielsens Vej 11, DK-2400, Copenhagen, Denmark
| | - Michael Kjaer
- Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Nielsine Nielsens Vej 11, building 8, 1st floor, DK-2400, Copenhagen, Denmark.,Center for Healthy Aging, Department of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, DK-2200, Copenhagen, N, Denmark
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8
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Skovgaard D, Svensson RB, Scheijen J, Eliasson P, Mogensen P, Hag AMF, Kjær M, Schalkwijk CG, Schjerling P, Magnusson SP, Couppé C. An advanced glycation endproduct (AGE)-rich diet promotes accumulation of AGEs in Achilles tendon. Physiol Rep 2017; 5:5/6/e13215. [PMID: 28336820 PMCID: PMC5371572 DOI: 10.14814/phy2.13215] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Revised: 02/23/2017] [Accepted: 02/27/2017] [Indexed: 12/13/2022] Open
Abstract
Advanced Glycation Endproducts (AGEs) accumulate in long‐lived tissue proteins like collagen in bone and tendon causing modification of the biomechanical properties. This has been hypothesized to raise the risk of orthopedic injury such as bone fractures and tendon ruptures. We evaluated the relationship between AGE content in the diet and accumulation of AGEs in weight‐bearing animal Achilles tendon. Two groups of mice (C57BL/6Ntac) were fed with either high‐fat diet low in AGEs high‐fat diet (HFD) (n = 14) or normal diet high in AGEs (ND) (n = 11). AGE content in ND was six to 50‐fold higher than HFD. The mice were sacrificed at week 40 and Achilles and tail tendons were carefully excised to compare weight and nonweight‐bearing tendons. The amount of the AGEs carboxymethyllysine (CML), methylglyoxal‐derived hydroimidazolone (MG‐H1) and carboxyethyllysine (CEL) in Achilles and tail tendon was measured using ultraperformance liquid chromatography tandem mass spectrometry (UPLC‐MS/MS) and pentosidine with high‐pressure liquid chromatography (HPLC) with fluorescent detection. AGEs in Achilles tendon were higher than in tail tendon for CML (P < 0.0001), CEL (P < 0.0001), MG‐H1 and pentosidine (for both ND and HFD) (P < 0.0001). The AGE‐rich diet (ND) resulted in an increase in CML (P < 0.0001), MG‐H1 (P < 0.001) and pentosidine (P < 0.0001) but not CEL, in Achilles and tail tendon. This is the first study to provide evidence for AGE accumulation in injury‐prone, weight‐bearing Achilles tendon associated with intake of an AGE‐rich diet. This indicates that food‐derived AGEs may alter tendon properties and the development of tendon injuries.
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Affiliation(s)
- Dorthe Skovgaard
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Rene B Svensson
- Department of Orthopedic Surgery M, Institute of Sports Medicine and IOC Research Centre Copenhagen, Bispebjerg Hospital and Center for Healthy Aging Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark
| | - Jean Scheijen
- Experimental Internal Medicine at the Faculty of Health, Medicine and Life Sciences Maastricht University Medical Center, Copenhagen, The Netherlands
| | - Pernilla Eliasson
- Department of Orthopedic Surgery M, Institute of Sports Medicine and IOC Research Centre Copenhagen, Bispebjerg Hospital and Center for Healthy Aging Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark
| | - Pernille Mogensen
- Department of Orthopedic Surgery M, Institute of Sports Medicine and IOC Research Centre Copenhagen, Bispebjerg Hospital and Center for Healthy Aging Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark
| | - Anne Mette F Hag
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging Rigshospitalet and University of Copenhagen, Copenhagen, Denmark
| | - Michael Kjær
- Department of Orthopedic Surgery M, Institute of Sports Medicine and IOC Research Centre Copenhagen, Bispebjerg Hospital and Center for Healthy Aging Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark
| | - Casper G Schalkwijk
- Experimental Internal Medicine at the Faculty of Health, Medicine and Life Sciences Maastricht University Medical Center, Copenhagen, The Netherlands
| | - Peter Schjerling
- Department of Orthopedic Surgery M, Institute of Sports Medicine and IOC Research Centre Copenhagen, Bispebjerg Hospital and Center for Healthy Aging Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark
| | - Stig P Magnusson
- Department of Orthopedic Surgery M, Institute of Sports Medicine and IOC Research Centre Copenhagen, Bispebjerg Hospital and Center for Healthy Aging Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark.,Department of Physical Therapy, Musculoskeletal Rehabilitation Research Unit Bispebjerg Hospital University of Copenhagen, Copenhagen, Denmark
| | - Christian Couppé
- Department of Orthopedic Surgery M, Institute of Sports Medicine and IOC Research Centre Copenhagen, Bispebjerg Hospital and Center for Healthy Aging Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark .,Department of Physical Therapy, Musculoskeletal Rehabilitation Research Unit Bispebjerg Hospital University of Copenhagen, Copenhagen, Denmark
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9
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Guilbaud A, Niquet-Leridon C, Boulanger E, Tessier FJ. How Can Diet Affect the Accumulation of Advanced Glycation End-Products in the Human Body? Foods 2016; 5:foods5040084. [PMID: 28231179 PMCID: PMC5302422 DOI: 10.3390/foods5040084] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2016] [Revised: 11/29/2016] [Accepted: 11/30/2016] [Indexed: 02/07/2023] Open
Abstract
The accumulation of advanced glycation end products (AGEs) is associated with the complications of diabetes, kidney disease, metabolic disorders and degenerative diseases. It is recognized that the pool of glycation products found in the human body comes not only from an endogenous formation, but also from a dietary exposure to exogenous AGEs. In recent years, the development of pharmacologically-active ingredients aimed at inhibiting endogenous glycation has not been successful. Since the accumulation of AGEs in the human body appears to be progressive throughout life, an early preventive action against glycation could be effective through dietary adjustments or supplementation with purified micronutrients. The present article provides an overview of current dietary strategies tested either in vitro, in vivo or both to reduce the endogenous formation of AGEs and to limit exposure to food AGEs.
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Affiliation(s)
- Axel Guilbaud
- University Lille, Inserm, CHU Lille, U995-LIRIC-Lille Inflammation Research International Center, F-59000 Lille, France.
| | | | - Eric Boulanger
- University Lille, Inserm, CHU Lille, U995-LIRIC-Lille Inflammation Research International Center, F-59000 Lille, France.
| | - Frederic J Tessier
- University Lille, Inserm, CHU Lille, U995-LIRIC-Lille Inflammation Research International Center, F-59000 Lille, France.
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10
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Roncero-Ramos I, Niquet-Léridon C, Strauch C, Monnier VM, Tessier FJ, Navarro MP, Delgado-Andrade C. An advanced glycation end product (AGE)-rich diet promotes Nε-carboxymethyl-lysine accumulation in the cardiac tissue and tendons of rats. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2014; 62:6001-6006. [PMID: 24892987 DOI: 10.1021/jf501005n] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
The purpose of this study was to investigate the intake, excretion, and tissue accumulation of carboxymethyl-lysine (CML), after feeding rats a diet containing advanced glycation end products (AGEs) from a glucose-lysine (GL) model system. Rats were distributed into two groups and assigned to a control diet or a diet including 3% heated GL (GL diet) for three months. Feces and urine were collected over the last week. After sacrifice, serum was obtained and some organs were removed for CML analysis. The percentage of fecal CML was 2.5-fold higher in the animals fed the GL diet (33.2 vs 76.5% for control and GL group), whereby total recovery was 91.8% compared with a level of 54.6% in the animals fed the control chow, evidencing the importance of the chemical form and the net quantity of dietary CML on its elimination. We suggest that dietary dicarbonyl compounds from GL diet or dietary CML itself are responsible for CML accumulation in hearts and tendons. The most significant result of the present study is that the regular consumption of dietary AGEs in healthy individuals promotes CML accumulation in some organs.
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Affiliation(s)
- Irene Roncero-Ramos
- Instituto en Formación de Nutrición Animal, Estación Experimental del Zaidín, CSIC, 18100, Granada, Spain
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Svistounov D, Oteiza A, Zykova SN, Sørensen KK, McCourt P, McLachlan AJ, McCuskey RS, Smedsrød B. Hepatic disposal of advanced glycation end products during maturation and aging. Exp Gerontol 2013; 48:549-56. [PMID: 23531498 DOI: 10.1016/j.exger.2013.03.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2012] [Revised: 02/06/2013] [Accepted: 03/16/2013] [Indexed: 01/10/2023]
Abstract
UNLABELLED Aging is characterized by progressive loss of metabolic and biochemical functions and accumulation of metabolic by-products, including advanced glycation end products (AGEs), which are observed in several pathological conditions. A number of waste macromolecules, including AGEs are taken up from the circulation by endocytosis mainly into liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs). However, AGEs still accumulate in different tissues with aging, despite the presence of this clearance mechanism. The aim of the present study was to determine whether the efficiency of LSECs and KCs for disposal of AGEs changes through aging. RESULTS After intravenous administration of (14)C-AGE-albumin in pre-pubertal, young adult, middle aged and old mice, more than 90% of total recovered (14)C-AGE was liver associated, irrespective of age. LSECs and KCs represented the main site of uptake. A fraction of the (14)C-AGE degradation products ((14)C-AGE-DPs) was stored for months in the lysosomes of these cells after uptake. The overall rate of elimination of (14)C-AGE-DPs from the liver was markedly faster in pre-pubertal than in all post-pubertal age groups. The ability to eliminate (14)C-AGE-DPs decreased to similar extents after puberty in LSECs and KCs. A rapid early removal phase was characteristic for all age groups except the old group, where this phase was absent. CONCLUSIONS Removal of AGE-DPs from the liver scavenger cells is a very slow process that changes with age. The ability of these cells to dispose of AGEs declines after puberty. Decreased AGE removal efficiency early in life may lead to AGE accumulation.
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Affiliation(s)
- Dmitri Svistounov
- Department of Medical Biology, University of Tromsø, Tromsø, Norway.
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12
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Roncero-Ramos I, Delgado-Andrade C, Tessier FJ, Niquet-Léridon C, Strauch C, Monnier VM, Navarro MP. Metabolic transit of N(ε)-carboxymethyl-lysine after consumption of AGEs from bread crust. Food Funct 2013; 4:1032-9. [PMID: 23435675 DOI: 10.1039/c3fo30351a] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Our aim was to investigate carboxymethyl-lysine (CML) intake and excretion after feeding rats with diets containing advanced glycation end-products (AGEs) from bread crust (BC) or its soluble or insoluble fractions, and to identify the factors responsible for the effects observed. CML in serum and different tissues was measured to detect possible accumulations. For 88 days, weanling rats were fed with either a control diet or one containing BC, or its soluble low molecular weight (LMW), soluble high molecular weight (HMW) or insoluble fractions. In the last week of the assay, faeces and urine were collected daily and stored as a 1 week pool. After sacrifice, blood was drawn to obtain serum and some organs were removed. CML analysis was performed by HPLC/MS/MS in diets, faeces, urines, serum and tissues. Faecal excretion of CML was strongly influenced by dietary CML levels and represents the major route of excretion (i.e. 33.2%). However, the urinary elimination of CML was probably limited or saturated, especially when more complex compounds were present in the diet. BC consumption increased CML in the cardiac tissue (170 ± 18 vs. 97 ± 3 μmol per mol lysine for BC and control groups), which correlated with the CML intake. The levels of this AGE in bone were unaffected by the dietary treatment, but in tail tendons CML was greatly increased in the animals that consumed the BC diet (102 ± 13 vs. 51 ± 8 μmol per mol lysine for BC and control groups, P = 0.006), which was associated with the intake of soluble LMW compounds present in BC. Despite the CML accumulation detected in different tissues, serum levels of protein-bound CML were unchanged, indicating the importance of measuring the free CML in this fluid as a real index of dietary CML.
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Affiliation(s)
- Irene Roncero-Ramos
- Instituto en Formación de Nutrición Animal, Estación Experimental del Zaidín, CSIC, Camino del Jueves s/n, 18100, Armilla, Granada, Spain
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13
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Yashin AI, Arbeev KG, Wu D, Arbeeva LS, Kulminski A, Akushevich I, Culminskaya I, Stallard E, Ukraintseva SV. How lifespan associated genes modulate aging changes: lessons from analysis of longitudinal data. Front Genet 2013; 4:3. [PMID: 23346098 PMCID: PMC3551204 DOI: 10.3389/fgene.2013.00003] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Accepted: 01/04/2013] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND AND OBJECTIVE The influence of genes on human lifespan is mediated by biological processes that characterize body's functioning. The age trajectories of these processes contain important information about mechanisms linking aging, health, and lifespan. The objective of this paper is to investigate regularities of aging changes in different groups of individuals, including individuals with different genetic background, as well as their connections with health and lifespan. DATA AND METHOD To reach this objective we used longitudinal data on four physiological variables, information about health and lifespan collected in the Framingham Heart Study (FHS), data on longevity alleles detected in earlier study, as well as methods of statistical modeling. RESULTS We found that phenotypes of exceptional longevity and health are linked to distinct types of changes in physiological indices during aging. We also found that components of aging changes differ in groups of individuals with different genetic background. CONCLUSIONS These results suggest that factors responsible for exceptional longevity and health are not necessary the same, and that postponing aging changes is associated with extreme longevity. The genetic factors which increase lifespan are associated with physiological changes typical of healthy and long-living individuals, smaller mortality risks from cancer and CVD and better estimates of adaptive capacity in statistical modeling. This indicates that extreme longevity and health related traits are likely to be less heterogeneous phenotypes than lifespan, and studying these phenotypes separately from lifespan may provide additional information about mechanisms of human aging and its relation to chronic diseases and lifespan.
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Dammann P, Sell DR, Begall S, Strauch C, Monnier VM. Advanced glycation end-products as markers of aging and longevity in the long-lived Ansell's mole-rat (Fukomys anselli). J Gerontol A Biol Sci Med Sci 2012; 67:573-83. [PMID: 22156473 PMCID: PMC3348492 DOI: 10.1093/gerona/glr208] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2011] [Accepted: 10/15/2011] [Indexed: 01/12/2023] Open
Abstract
Mole-rat of the genus Fukomys are mammals whose life span is strongly influenced by reproductive status with breeders far outliving nonbreeders. This raises the important question of whether increased longevity of the breeders is reflected in atypical expression of biochemical markers of aging. Here, we measured markers of glycation and advanced glycation end-products formed in insoluble skin collagen of Ansell's mole-rat Fukomys anselli as a function of age and breeding status. Glucosepane, pentosidine, and total advanced glycation end-product content significantly increased with age after correction for breeder status and sex. Unexpectedly, total advanced glycation end-products, glucosepane, and carboxymethyl-lysine (CML) were significantly higher in breeders versus nonbreeders suggesting that breeders have evolved powerful defenses against combined oxidant and carbonyl stress compared with nonbreeders. Most interestingly, when compared with other mammals, pentosidine formation rate was lower in mole-rat compared with other short-lived rodents confirming previous observations of an inverse relationship between longevity and pentosidine formation rates in skin collagen.
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Affiliation(s)
- Philip Dammann
- Department of General Zoology, University of Duisburg-Essen, Germany
- Central Animal Laboratory, University Duisburg-Essen Medical School, Germany
| | | | - Sabine Begall
- Department of General Zoology, University of Duisburg-Essen, Germany
| | | | - Vincent M. Monnier
- Department of Pathology
- Department of Biochemistry, School of Medicine, Case Western Reserve University, Cleveland, Ohio
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15
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Sloane LB, Stout JT, Austad SN, McClearn GE. Tail tendon break time: a biomarker of aging? J Gerontol A Biol Sci Med Sci 2010; 66:287-94. [PMID: 21059835 DOI: 10.1093/gerona/glq196] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Research has attempted to identify biomarkers of aging that are predictive of longevity and specific age-related changes during animal life span. Tail tendon break time (TTBT), one presumed biomarker, measures collagen cross-linking, known to increase with age. Significant differences in the rate of increase of TTBT with age have been reported between mouse strains and animal species. We measured both TTBT and longevity in C57BL/6J, DBA/2J, and 23 recombinant inbred (RI) strains (B×D RIs), with TTBT measured at 200, 500, and 800 days of age. Longevity demonstrated considerable variability among these strains (116-951 days). TTBT, also highly variable, increased significantly with age in both sexes and all genotypes. Neither TTBT nor its rate of change correlated significantly with life span. There were suggestive trends for rate of TTBT change to correlate with male longevity and strain longevity to correlate with female TTBT. We conclude that for the range of genetic variation found among these mouse genotypes, TTBT cannot be considered a robust biomarker of longevity.
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Affiliation(s)
- Lauren B Sloane
- Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio, STCBM Room 3.325, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA.
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16
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Sloane LB, Stout JT, Vandenbergh DJ, Vogler GP, Gerhard GS, McClearn GE. Quantitative trait loci analysis of tail tendon break time in mice of C57BL/6J and DBA/2J lineage. J Gerontol A Biol Sci Med Sci 2010; 66:170-8. [PMID: 21047976 DOI: 10.1093/gerona/glq169] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Tail tendon break time (TTBT), a measure of collagen cross-linking, shown to increase with age differs significantly among inbred strains of mice, indicating underlying genetic influences. This study was aimed to identify quantitative trait loci (QTLs) associated with tail tendon break time at three ages (200, 500, and 800 days of age) for 23 BxD recombinant inbred strains of mice and B6D2F(2) mice derived from C57BL/6J and DBA/2J strains. Heritability estimates were calculated, and QTL analyses were conducted using interval-mapping methods. Mean tail tendon break time values were higher in males and increased nonlinearly with age. Eight total QTLs were nominated in the B6D2F(2) mice at the three measured ages, with the QTL at 800 days confirmed in the recombinant inbred strains. Allelic effect modeling for the identified QTLs suggests differences in gene action between sexes. Candidate genes in the QTL regions include collagen genes and an advanced glycation end-product receptor. The QTLs identified demonstrate influence at some but not all ages.
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Affiliation(s)
- Lauren B Sloane
- Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center, STCBM Room 3.325, 15355 Lambda Drive, San Antonio, TX 78245-3207, USA.
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17
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Gineyts E, Munoz F, Bertholon C, Sornay-Rendu E, Chapurlat R. Urinary levels of pentosidine and the risk of fracture in postmenopausal women: the OFELY study. Osteoporos Int 2010; 21:243-50. [PMID: 19421701 DOI: 10.1007/s00198-009-0939-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2009] [Accepted: 04/10/2009] [Indexed: 01/22/2023]
Abstract
UNLABELLED The aim of the study was to investigate prospectively whether the levels of urinary pentosidine could predict fractures in postmenopausal women from the OFELY cohort. The results of the study suggest that urine pentosidine concentration is not an independent risk factor for fractures in postmenopausal women from a French cohort. INTRODUCTION Pentosidine has been described as an independent risk factor for hip and vertebral fracture in postmenopausal Japanese women. We investigated the prediction of urinary pentosidine on all fragility fracture risk in healthy untreated postmenopausal women from the OFELY cohort. METHODS Urinary pentosidine was assessed at baseline in 396 healthy untreated postmenopausal women aged 63.3 +/- 8.4 years from the OFELY cohort using high-performance liquid chromatography method. Incident clinical fractures were recorded during annual follow-up and confirmed by radiographs, and vertebral fractures were assessed on radiographs performed every 4 years. Multivariate Cox's regression analysis was used to calculate the risk of urinary pentosidine levels after adjustment for age, prevalent fractures, and total hip bone mineral density (BMD). RESULTS During a mean follow-up of 10 years, 88 of the 396 postmenopausal women have undergone incident vertebral (n = 28) and peripheral (n = 60) fractures. Fracture risk was higher in postmenopausal women with pentosidine in the highest quartile (p = 0.02), but it did not remain significant after adjustment for age, BMD, and prevalent fracture. CONCLUSIONS Urine pentosidine concentration is not an independent risk factor of osteoporotic fracture in healthy postmenopausal women from the OFELY cohort.
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Affiliation(s)
- E Gineyts
- Hôpital Edouard Herriot, pavillon F, INSERM Research Unit 831, 69437, Lyon cedex 03, France.
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18
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Rutter K, Sell DR, Fraser N, Obrenovich M, Zito M, Starke-Reed P, Monnier VM. Green tea extract suppresses the age-related increase in collagen crosslinking and fluorescent products in C57BL/6 mice. INT J VITAM NUTR RES 2004; 73:453-60. [PMID: 14743550 PMCID: PMC3561737 DOI: 10.1024/0300-9831.73.6.453] [Citation(s) in RCA: 54] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
Collagen crosslinking during aging in part results from Maillard reaction endproducts of glucose and oxoaldehydes. Because of the tight link between oxidative and carbonyl stress, we hypothesized that natural antioxidants and "nutriceuticals" could block collagen aging in C57BL/6 mice. Six groups of young and adult mice received vitamin C, vitamin E, vitamin C&E, blueberry, green tea extract (GTE), or no treatment for a period of 14 weeks. Body weights and collagen glycation were unaltered by the treatment. However, GTE or vitamin C&E combined blocked tendon crosslinking at 10 months of age (p < 0.05, adult group). GTE also blocked fluorescent products at 385 and 440 nm (p = 0.052 and < 0.05, respectively) and tended to decrease skin pentosidine levels. These results suggest that green tea is able to delay collagen aging by an antioxidant mechanism that is in part duplicated by the combination of vitamin C and E.
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Affiliation(s)
| | - David R. Sell
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
| | | | - Mark Obrenovich
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
| | | | - Pamela Starke-Reed
- National Institute of Diabetes, Digestive and Kidney Diseases, NIH, 31 Center Drive, MSC 2560, Bethesda, MD 20892-2560, USA
| | - Vincent M. Monnier
- Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA
- Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA
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19
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Iwashige K, Kouda K, Kouda M, Horiuchi K, Takahashi M, Nagano A, Tanaka T, Takeuchi H. Calorie Restricted Diet and Urinary Pentosidine in Patients with Rheumatoid Arthritis. ACTA ACUST UNITED AC 2004; 23:19-24. [PMID: 14757997 DOI: 10.2114/jpa.23.19] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
Low-energy diets and fasting have suppressive effects on rheumatoid arthritis. It was reported recently that urine levels of pentosidine (i.e., an advanced glycation end product formed by glycosylation) is associated with the activity of rheumatoid arthritis. We conducted a regimen of caloric restriction combined with fasting in patients with rheumatoid arthritis, and then evaluated urinary pentosidine levels. Ten patients with rheumatoid arthritis underwent a 54-day caloric restriction program. Urinary pentosidine levels were measured and the Lansbury Index were determined by examining the clinical features, blood biochemistry and the inflammation activity of rheumatoid arthritis on days 0, 25 and 54. On day 0, the mean urinary pentosidine level of patients with rheumatoid arthritis was significantly higher than that of the control subjects. On day 54, the mean body weight had reduced due to caloric restriction. The mean values of the erythrocyte sedimentation rate and the Lansbury Index of patients both significantly decreased during the study. In addition, although the urinary pentosidine levels showed no significant difference between day 0 and 25, it was significantly decreased at the end of the study (day 54). The study showed that under a low energy diet a reduction of disease activity in rheumatoid arthritis was accompanied with a reduction of the urinary pentosidine.
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Affiliation(s)
- Kenichi Iwashige
- Department of Public Health, Hamamatsu University School of Medicine, Japan.
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20
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Abstract
The field of Maillard/glycation reactions in vivo has grown enormously during the past 20 years, going from 25 to 500 publications per year. It is now well recognized that many of the "advanced" products form oxidatively or anaerobically and can have deleterious effects on macromolecular and biological function. The feasibility of developing pharmacological agents with beneficial in vivo properties, based on in vitro inhibition of glycation, has been surprisingly successful. This Editorial sets the stage for a series of articles by experts in the field, who have made key contributions to our understanding of the Maillard reaction in vivo.
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21
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DeGroot J, Verzijl N, Wenting-Van Wijk MJ, Bank RA, Lafeber FP, Bijlsma JW, TeKoppele JM. Age-related decrease in susceptibility of human articular cartilage to matrix metalloproteinase-mediated degradation: the role of advanced glycation end products. ARTHRITIS AND RHEUMATISM 2001; 44:2562-71. [PMID: 11710713 DOI: 10.1002/1529-0131(200111)44:11<2562::aid-art437>3.0.co;2-1] [Citation(s) in RCA: 89] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Progressive destruction of articular cartilage is a hallmark of osteoarthritis (OA) and rheumatoid arthritis (RA). Age-related changes in cartilage may influence tissue destruction and thus progression of the disease. Therefore, the effect of age-related accumulation of advanced glycation end products (AGEs) on cartilage susceptibility to proteolytic degradation by matrix metalloproteinases (MMPs) present in synovial fluid (SF) of OA and RA patients was studied. METHODS Cartilage was incubated with APMA-activated SF obtained from OA or RA patients, and tissue degradation was assessed by colorimetric measurement of glycosaminoglycan (GAG) release. Cartilage degradation was related to the level of AGEs in cartilage from donors of different ages (33-83 years) and in cartilage with in vitro-enhanced AGE levels (by incubation with ribose). MMP activity in SF was measured using a fluorogenic substrate. AGE levels were assessed by high-performance liquid chromatography measurement of the glycation product pentosidine. RESULTS In cartilage from donors ages 33-83 years, a strong correlation was found between the age-related increase in pentosidine and the decrease in MMP-mediated tissue degradation (r = -0.74, P < 0.0005). Multiple regression analysis showed pentosidine to be the strongest predictor of the decreased GAG release (P < 0.0005); age did not contribute (P > 0.8). In addition, decreased MMP-mediated GAG release was proportional to increased pentosidine levels after in vitro enhancement of glycation (r = -0.27, P < 0.01). This was demonstrated for both OA and RA SF (for control versus glycated, P < 0.002 for all SF samples tested). CONCLUSION Increased cartilage AGEs resulted in decreased cartilage degradation by MMPs from SF, indicating that aged cartilage is less sensitive than young cartilage to MMP-mediated cartilage degradation, such as occurs in OA and RA. Therefore, the level of cartilage glycation may influence the progression of these diseases.
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Affiliation(s)
- J DeGroot
- Gaubius Laboratory, TNO Prevention and Health, Leiden, The Netherlands.
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22
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Sell DR, Nelson JF, Monnier VM. Effect of chronic aminoguanidine treatment on age-related glycation, glycoxidation, and collagen cross-linking in the Fischer 344 rat. J Gerontol A Biol Sci Med Sci 2001; 56:B405-11. [PMID: 11524442 DOI: 10.1093/gerona/56.9.b405] [Citation(s) in RCA: 40] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023] Open
Abstract
Aminoguanidine (AG) is an inhibitor of protein modification by the advanced Maillard reaction. We evaluated its effects in preventing age-related collagen cross-linking, glycation, and glycoxidation in Fischer 344 rats by administering the drug in their drinking water at 1 g/l from the time they were 6 months until they were 24 months of age. Body weight and food and water consumption were consistently recorded throughout the study. Plasma glucose was measured by the glucose oxidase method, and collagen cross-linking was assessed by tail tendon break time (TBT) in urea. Glycation (furosine) and glycoxidation (pentosidine and carboxymethyllysine) were assessed by high-performance liquid chromatography in acid hydrolysates of skin and tendon collagen. Water consumption dramatically increased (p <.0001) after 20 months of age and was accelerated in the control versus AG-treated rats (p <.0001). Plasma glucose increased approximately 20% at age 19 months in both groups (p <.0001). TBT, glycation, and glycoxidation all increased significantly (p <.0001) with age. However, except for a modest decrease of TBT at all ages that approached significance (p =.077), AG had no effect on collagen glycation or glycoxidation. These results are important because they suggest that alpha,beta-dicarbonyl compounds that can be trapped by aminoguanidine do not play a major role in collagen aging in the rat. Instead, post-Amadori pathways involving oxidative or nonoxidative fragmentation of the Amadori product emerge as the more likely mechanism of collagen cross-linking in aging.
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Affiliation(s)
- D R Sell
- Institute of Pathology, Case Western Reserve University, 2085 Adelbert Road, Cleveland, OH 44106, USA.
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23
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Stefek M, Gajdosik A, Gajdosikova A, Krizanova L. p-Dimethylaminobenzaldehyde-reactive substances in tail tendon collagen of streptozotocin-diabetic rats: temporal relation to biomechanical properties and advanced glycation endproduct (AGE)-related fluorescence. BIOCHIMICA ET BIOPHYSICA ACTA 2000; 1502:398-404. [PMID: 11068182 DOI: 10.1016/s0925-4439(00)00064-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
In the present work, pepsin digests of tail tendons from streptozotocin-diabetic rats were found to contain material that reacted rapidly at room temperature with p-dimethylaminobenzaldehyde (Ehrlich's reagent) to give an adduct with an absorbance spectrum characteristic of the Ehrlich chromogen of pyrrolic nature determined in ageing collagens. A significant correlation of the Ehrlich adduct with tendon mechanical strength and collagen fluorescence characteristic of advanced glycation endproducts was observed. Collagen content of the Ehrlich-positive material was found to be significantly elevated in tendons of diabetic rats compared with age-matched healthy controls. The results indicate that the p-dimethylaminobenzaldehyde-reactive pyrrole moieties may contribute to the increased cross-linking of diabetic matrix collagen. Profound inhibitory effect of aminoguanidine was observed, underlining the role of non-enzymatic mechanisms of advanced glycation in pyrrolisation and cross-linking of collagen exposed to hyperglycaemia. It is hypothesised that quantification of the p-dimethylaminobenzaldehyde-reactive material in matrix collagen may provide a tissue measure of integrated hyperglycaemia over prolonged periods of time. Further research is to assess the significance of p-dimethylaminobenzaldehyde-reactive substances in diabetic collagen tissues and to reveal their relationship to enzyme-mediated physiological pyrrolisation of ageing collagens.
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Affiliation(s)
- M Stefek
- Institute of Experimental Pharmacology, Slovak Academy of Sciences, Dubravska cesta 9, 842 16, Bratislava, Slovakia.
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24
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Iqbal M, Kenney PB, Al-Humadi NH, Klandorf H. Relationship between mechanical properties and pentosidine in tendon: effects of age, diet restriction, and aminoguanidine in broiler breeder hens. Poult Sci 2000; 79:1338-44. [PMID: 11020082 DOI: 10.1093/ps/79.9.1338] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Nonenzymatic glycosylation contributes to the formation of crosslinks, which leads to the structural and functional deterioration of tissue protein. The accumulation of these crosslinks in tissue proteins has been implicated in the alteration of biomechanical properties of connective tissues. The objective of this study was to determine whether tendon breaking time (TBT) and tendon breaking strength (TBS) of the flexor perforans et perforatus digiti iii tendon were related to concentrations of pentosidine in tendons (Pt) of broiler breeder hens from 8 to 125 wk of age. In addition, effects of diet restriction (DR) and a crosslinking inhibitor, aminoguanidine (AG) on Pt, TBS, and TBT were determined. Female chicks (n = 450) were randomly assigned to four treatment groups immediately after hatch: ad libitum-fed (AL); diet-restricted (DR; 60% of AL); and AL and DR groups supplemented with 1.35 mg/kg BW per day AG in the feed (AL+AG and DR+AG, respectively). In AL hens, Pt increased with increasing age (P < or = 0.0001). Concurrently, an age-related parallel increase was found for TBS (P < or = 0.0001) and TBT (P < or = 0.0001). Rate of Pt accumulation was lower in DR (P < or = 0.001), TBS (P < or = 0.01), and TBT (P < or = 0.02) hens compared with AL hens. Concentration of Pt in the AL + AG group was lower (P < or = 0.0002) than in the AL group; TBS and TBT (P < or = 0.01) followed a similar pattern. Supplementation of DR with AG did not affect Pt, TBS, or TBT. The age-related increase in Pt and loss of elasticity in the tendon was retarded by diet restriction and AG.
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Affiliation(s)
- M Iqbal
- Division of Animal and Veterinary Sciences, College of Agriculture, Forestry, and Consumer Sciences, West Virginia University, Morgantown 26506-6108, USA
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25
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Lingelbach LB, Mitchell AE, Rucker RB, McDonald RB. Accumulation of advanced glycation endproducts in aging male Fischer 344 rats during long-term feeding of various dietary carbohydrates. J Nutr 2000; 130:1247-55. [PMID: 10801926 DOI: 10.1093/jn/130.5.1247] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
The observation of accelerated collagen glycation in association with enhanced progression of many age-associated diseases in hyperglycemic subjects has led researchers to propose a role of glycation in the aging process. Although short-term studies in healthy animals suggest that feeding a diet high in fructose may increase serum glucose concentrations and increase glycemic stress, the effects of a long-term feeding, i.e., life span, are unknown. This study was designed to evaluate the long-term effects of dietary carbohydrates on serum and tissue markers of glycemic stress. Three-month-old male Fischer 344 rats were given free access to or restricted to 60% caloric intake of one of five isocaloric diets that contained as their carbohydrate source either cornstarch, glucose, sucrose, fructose or equimolar amounts of fructose and glucose. Rats were killed at 9-, 18- or 26-mo of age. Glycated hemoglobin, serum glucose and fructosamine levels were measured as markers of serum glycemic stress. Collagen-associated fluorescence and pentosidine concentrations were measured in skin, aortic, tracheal and tail tendon collagen as markers of advanced glycation endproducts (AGE). The source of dietary carbohydrate had little effect on markers of glycemic stress and the accumulation of AGE. Restricting the amount of calories consumed resulted in lower serum glucose concentrations, glycated hemoglobin levels and pentosidine concentrations in tail tendon collagen. Our data suggest that the rate of collagen glycation is tissue-specific. These results suggest that long-term feeding of specific dietary carbohydrates does not alter serum glucose concentrations or the rate of collagen glycation. Rather, age-related accumulation of AGE is more closely related to caloric intake.
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Affiliation(s)
- L B Lingelbach
- Department of Nutrition, University of California, Davis, CA 95616-8669, USA
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Sell DR, Kleinman NR, Monnier VM. Longitudinal determination of skin collagen glycation and glycoxidation rates predicts early death in C57BL/6NNIA mice. FASEB J 2000; 14:145-56. [PMID: 10627289 DOI: 10.1096/fasebj.14.1.145] [Citation(s) in RCA: 76] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
In 1988, the National Institute on Aging launched a 10-year program aimed at identification of biomarkers of aging. Previous results from our laboratory showed that pentosidine, an advanced glycation product, formed in skin collagen at a rate inversely related to maximum life span across several mammalian species. As part of the Biomarkers Program, we investigated the hypothesis that longitudinal determination of glycation and glycoxidation rates in skin collagen could predict longevities in ad libitum-fed (AL) and caloric restricted (CR) mice. C57BL/6NNia male mice were biopsied at age 20 months and at natural death. Glycation (furosine method) was assessed by gas chromatography/mass spectrometry (GC/MS) and the glycoxidation products carboxymethyllysine (CML) and pentosidine were determined by GC/MS and HPLC, respectively. CR vs. AL significantly (P<0.0001) increased both mean (34 vs. 27 months) and maximum (47 vs. 31 months) life spans. Skin collagen levels of furosine (pmol/micromol lysine) were approximately 2.5-fold greater than CML levels and 100-fold greater than pentosidine. Individual accumulation rates modeled as linear equations were significantly (P<0.001) inhibited by CR vs. AL for all parameters and in all cases varied inversely with longevity (P<0.1 to <0.0001). The incidence of three tissue pathologies (lymphoma, dermatitis, and seminal vesiculitis) was found to be attenuated by CR and the latter pathology correlated significantly with longevities (r=0.54, P=0. 002). The finding that markers of skin collagen glycation and glycoxidation rates can predict early deaths in AL and CR C57BL/6NNia mice strongly suggests that an age-related deterioration in glucose tolerance is a life span-determining process.
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Affiliation(s)
- D R Sell
- Institute of Pathology and. Animal Resource Center, Case Western Reserve University, Cleveland, Ohio 44106, USA.
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