Involvement of insulin resistance in D-galactose-induced age-related dementia in rats: Protective role of metformin and saxagliptin

Atherosclerotic disease, such as coronary artery disease (CAD), is known to be a chronic inflammatory disease, as well as an age-related disease. Excessive oxidative stress produced by reactive oxygen species (ROS) contributes to the pathogenesis of atherosclerosis. Sestrin2 is an anti-oxidant protein that is induced by various stresses such as hypoxia, DNA damage, and oxidative stress. Sestrin2 is also suggested to be associated with aging. Sestrin2 is expressed and secreted mainly by macrophages, endothelial cells, and cardiomyocytes. Sestrin2 plays an important role in suppressing the production and accumulation of ROS, thus protecting cells from oxidative damage. Since sestrin2 is reported to have anti-oxidant and anti-inflammatory properties, it may play a protective role against the progression of atherosclerosis and may be a potential therapeutic target for the amelioration of atherosclerosis. Regarding the association between blood sestrin2 levels and atherosclerotic disease, the blood sestrin2 levels in patients with CAD or carotid atherosclerosis were reported to be high. High blood sestrin2 levels in patients with such atherosclerotic disease may reflect a compensatory response to increased oxidative stress and may help protect against the progression of atherosclerosis. This review describes the protective role of sestrin2 against the progression of atherosclerotic and cardiac diseases.

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Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

Orvosi Hetilap ◽

10.1556/650.2021.32200 ◽

2021 ◽

Vol 162 (33) ◽

pp. 1318-1327

Author(s):

Tamás Halmos ◽

Ilona Suba

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Life Expectancy ◽

Significant Risk ◽

Low Grade ◽

Aging Effects ◽

Protective Function ◽

Beneficial Effects ◽

Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

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The Protective Role of Exercise Against Age-Related Neurodegeneration

Ageing Research Reviews ◽

10.1016/j.arr.2021.101543 ◽

2021 ◽

pp. 101543

Author(s):

Alyson L. Sujkowski ◽

Luke Hong ◽

R.J. Wessells ◽

Sokol V. Todi

Keyword(s):

Protective Role ◽

Age Related

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Protocatechuic acids protects against high glucose- induced insulin resistance in human visceral adipose tissue

Problems of Endocrinology ◽

10.14341/probl201662545-46 ◽

2016 ◽

Vol 62 (5) ◽

pp. 45-46

Author(s):

Paulina Ormazabal ◽

Beatrice Scazzocchio ◽

Rosaria Varì ◽

Annunziata Iacovelli ◽

Roberta Masella

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Visceral Adipose Tissue ◽

High Glucose ◽

Protective Role ◽

Insulin Sensitizer ◽

20 Nm ◽

Visceral Adipose

Adipocytes exposed to high glucose concentrations exhibit impaired insulin signaling. Binding of insulin to its membrane receptor activates insulin metabolic pathway leading to IRS-1 and AKT phosphorylations. The accumulation of visceral adipose tissue (VAT) correlates with insulin resistance and metabolic syndrome. Anthocyanins (ACN) are bioactive food compounds of great nutritional interest. We have shown that protocatechuic acid (PCA), a major metabolite of ACN, might exert insulin-sensitizer activities in human visceral adipose tissue. The aim of this work was to define the protective role of PCA against insulin-resistance induced by high glucose in VAT.Methodology: VAT obtained from control subject (BMI≤25) were separated in four experimental groups: i) PCA: samples treated for 24 h with 100 μM PCA, ii) GLU: VAT treated with 30 mM glucose for 24 h, iii) PCA+GLU: 1 hour incubation with 100 μM PCA before adding glucose (30 mM, 24 h), iv) CTR: vehicle. After treatment, VAT groups were (or not) acutely stimulated with insulin (20 nM, 20 min). Tyr-IRS-1 and Ser-Akt phosphorylations were assessed by Western blotting (WB) in basal or insulin stimulated tissues in all experimental groups. Samples were assessed for IRS-1, IR, Akt and GLUT4 protein content by WB. Results: No differences in protein contents between experimental groups were found. GLU tissues showed a lower increment in insulin-stimulated phosphorylation of IRS-1 and Akt compared to CTR and PCA samples. This impaired activation was completely reversed by the pretreatment with PCA.Conclusion: An in-vitro insulin-resistance condition induced by high glucose was established in biopsies of VAT. PCA restores the ability of GLU-tissues to fully respond to insulin by increasing IRS-1 and Akt phosphorylations. These results confirm the insulin-sensitizer effect of PCA on VAT previously reported by our group. An anthocyanin rich diet might help to protect against insulin-resistance in VAT.

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Autophagy Protects Advanced Glycation End Product-Induced Apoptosis and Expression of MMP-3 and MMP-13 in Rat Chondrocytes

BioMed Research International ◽

10.1155/2017/6341919 ◽

2017 ◽

Vol 2017 ◽

pp. 1-9 ◽

Cited By ~ 5

Author(s):

Wenzhou Huang ◽

Peng Ao ◽

Jian Li ◽

Tianlong Wu ◽

Libiao Xu ◽

...

Keyword(s):

Western Blotting ◽

Annexin V ◽

Protective Role ◽

Autophagic Flux ◽

Advanced Glycation ◽

Age Related ◽

Glycation End Products ◽

Induced Apoptosis ◽

Related Proteins

Aging is one of the most prominent risk factors for the pathological progression of osteoarthritis (OA). One feature of age-related changes in OA is advanced glycation end products (AGEs) accumulation in articular cartilage. Autophagy plays a cellular housekeeping role by removing dysfunctional cellular organelles and proteins. However, the relationship between autophagy and AGE-associated OA is unknown. The aim of this study is to determine whether autophagy participates in the pathology of AGE-treated chondrocytes and to investigate the exact role of autophagy in AGE-induced cell apoptosis and expression of matrix metalloproteinase- (MMP-) 3 and MMP-13. AGEs induced notable apoptosis that was detected by Annexin V/PI double-staining, and the upregulation of MMP-3 and MMP-13 was confirmed by Western blotting. Autophagy-related proteins were also determined by Western blotting, and chondrocytes were transfected with mCherry-GFP-LC3B-adenovirus to monitor autophagic flux. As a result, autophagy significantly increased in chondrocytes and peaked at 6 h. Furthermore, rapamycin (RA) attenuated AGE-induced apoptosis and expression of MMP-3 and MMP-13 by autophagy activation. In contrast, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) enhanced the abovementioned effects of AGEs. We therefore demonstrated that autophagy is linked with AGE-related pathology in rat chondrocytes and plays a protective role in AGE-induced apoptosis and expression of MMP-3 and MMP-13.

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Diethyl Hexyl Phthalate (DEHP) is associated with insulin resistance in adipose tissue of male rat: Protective role of antioxidant vitamins (C & E)

Journal of Cellular Biochemistry ◽

10.1002/jcb.24399 ◽

2013 ◽

Vol 114 (3) ◽

pp. 558-569 ◽

Cited By ~ 43

Author(s):

Parsanathan Rajesh ◽

Sampath Sathish ◽

Chinnapaiyan Srinivasan ◽

Jayaraman Selvaraj ◽

Karundevi Balasubramanian

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Protective Role ◽

Antioxidant Vitamins ◽

Male Rat

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A Possible Role for the Antioxidants Lutein and Zeaxanthin in Protecting against Age-Related Increases in Lens Density

Perception ◽

10.1068/v970269 ◽

1997 ◽

Vol 26 (1_suppl) ◽

pp. 166-166

Author(s):

B R Hammond ◽

J E Náñez

Keyword(s):

Light Exposure ◽

Latency Period ◽

Crystalline Lens ◽

Epidemiological Data ◽

Protective Role ◽

Older Individuals ◽

Age Related ◽

Number Of Factors ◽

Relationship Of

Epidemiological data have identified a number of factors that influence risk of developing age-related cataract (ARC). For instance, factors that promote (eg smoking and light exposure) and factors that protect (eg antioxidants) against oxidative stress to the crystalline lens appear to increase and decrease risk of ARC, respectively. Although biochemical studies consistently support a protective role for antioxidants, the epidemiological data are inconsistent. Since ARC is a condition with a protracted latency period, it is possible that the inconsistencies present in the epidemiological literature may be due to the focus on cataractous patients. We focused on the lens health of individuals prior to cataract. Lens health was determined by measuring the optical density (OD) of the lens with a psychophysical technique. OD characterises many of the biochemical changes of the lens and is part of many systems used to classify ARC. Variance in lens OD, stratified by age, was examined for its relationship to variables thought to be important to the etiology of ARC. We report results for the relationship of lens OD to the antioxidants lutein and zeaxanthin (L and Z). For older individuals (>48 years) we noted a significant inverse relationship between dietary intake of L and Z and lens OD ( n=39, r=−0.34, p<0.015). This was not the case for younger individuals (24 – 36 years). This relationship is increased when L and Z are measured directly in the retina is a psychophysical technique. For older individuals, retinal L and Z (ie macular pigment) are inversely related to lens OD ( n=51, r=-0.47, p<0.001). These data are consistent with a role of L and Z in protecting against age-related increases in the OD of the crystalline lens.

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