Lessons Learned About Prostatic Transformation from the Age-Related Methylation of 5α-Reductase Type 2 Gene

Autophagy has been strongly linked with hormesis, however, it is only relatively recently that the mechanistic basis underlying this association has begun to emerge. Lysosomal autophagy is a group of processes that degrade proteins, protein aggregates, membranes, organelles, segregated regions of cytoplasm, and even parts of the nucleus in eukaryotic cells. These degradative processes are evolutionarily very ancient and provide a survival capability for cells that are stressed or injured. Autophagy and autophagic dysfunction have been linked with many aspects of cell physiology and pathology in disease processes; and there is now intense interest in identifying various therapeutic strategies involving its regulation. The main regulatory pathway for augmented autophagy is the mechanistic target of rapamycin (mTOR) cell signaling, although other pathways can be involved, such as 5′-adenosine monophosphate-activated protein kinase. Mechanistic target of rapamycin is a key player in the many highly interconnected intracellular signaling pathways and is responsible for the control of cell growth among other processes. Inhibition of mTOR (specifically dephosphorylation of mTOR complex 1) triggers augmented autophagy and the search is on the find inhibitors that can induce hormetic responses that may be suitable for treating many diseases, including many cancers, type 2 diabetes, and age-related neurodegenerative conditions.

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A Narrative Review on Sarcopenia in Type 2 Diabetes Mellitus: Prevalence and Associated Factors

Nutrients ◽

10.3390/nu13010183 ◽

2021 ◽

Vol 13 (1) ◽

pp. 183

Author(s):

Anna Izzo ◽

Elena Massimino ◽

Gabriele Riccardi ◽

Giuseppe Della Pepa

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Elderly Population ◽

The Elderly ◽

Narrative Review ◽

Macrovascular Complications ◽

Diabetic Patients ◽

Age Related

Type 2 diabetes mellitus (T2DM) represents a major health burden for the elderly population, affecting approximately 25% of people over the age of 65 years. This percentage is expected to increase dramatically in the next decades in relation to the increased longevity of the population observed in recent years. Beyond microvascular and macrovascular complications, sarcopenia has been described as a new diabetes complication in the elderly population. Increasing attention has been paid by researchers and clinicians to this age-related condition—characterized by loss of skeletal muscle mass together with the loss of muscle power and function—in individuals with T2DM; this is due to the heavy impact that sarcopenia may have on physical and psychosocial health of diabetic patients, thus affecting their quality of life. The aim of this narrative review is to provide an update on: (1) the risk of sarcopenia in individuals with T2DM, and (2) its association with relevant features of patients with T2DM such as age, gender, body mass index, disease duration, glycemic control, presence of microvascular or macrovascular complications, nutritional status, and glucose-lowering drugs. From a clinical point of view, it is necessary to improve the ability of physicians and dietitians to recognize early sarcopenia and its risk factors in patients with T2DM in order to make appropriate therapeutic approaches able to prevent and treat this condition.

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Hyperinsulinemia and Its Pivotal Role in Aging, Obesity, Type 2 Diabetes, Cardiovascular Disease and Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms22157797 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7797

Author(s):

Joseph A. M. J. L. Janssen

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Insulin Secretion ◽

Early Stage ◽

Insulin Clearance ◽

Future Research ◽

Age Related ◽

Hepatic Insulin Clearance

For many years, the dogma has been that insulin resistance precedes the development of hyperinsulinemia. However, recent data suggest a reverse order and place hyperinsulinemia mechanistically upstream of insulin resistance. Genetic background, consumption of the “modern” Western diet and over-nutrition may increase insulin secretion, decrease insulin pulses and/or reduce hepatic insulin clearance, thereby causing hyperinsulinemia. Hyperinsulinemia disturbs the balance of the insulin–GH–IGF axis and shifts the insulin : GH ratio towards insulin and away from GH. This insulin–GH shift promotes energy storage and lipid synthesis and hinders lipid breakdown, resulting in obesity due to higher fat accumulation and lower energy expenditure. Hyperinsulinemia is an important etiological factor in the development of metabolic syndrome, type 2 diabetes, cardiovascular disease, cancer and premature mortality. It has been further hypothesized that nutritionally driven insulin exposure controls the rate of mammalian aging. Interventions that normalize/reduce plasma insulin concentrations might play a key role in the prevention and treatment of age-related decline, obesity, type 2 diabetes, cardiovascular disease and cancer. Caloric restriction, increasing hepatic insulin clearance and maximizing insulin sensitivity are at present the three main strategies available for managing hyperinsulinemia. This may slow down age-related physiological decline and prevent age-related diseases. Drugs that reduce insulin (hyper) secretion, normalize pulsatile insulin secretion and/or increase hepatic insulin clearance may also have the potential to prevent or delay the progression of hyperinsulinemia-mediated diseases. Future research should focus on new strategies to minimize hyperinsulinemia at an early stage, aiming at successfully preventing and treating hyperinsulinemia-mediated diseases.

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Telomere Length and Oxidative Stress and Its Relation with Metabolic Syndrome Components in the Aging

Biology ◽

10.3390/biology10040253 ◽

2021 ◽

Vol 10 (4) ◽

pp. 253

Author(s):

Graciela Gavia-García ◽

Juana Rosado-Pérez ◽

Taide Laurita Arista-Ugalde ◽

Itzen Aguiñiga-Sánchez ◽

Edelmiro Santiago-Osorio ◽

...

Keyword(s):

Oxidative Stress ◽

Metabolic Syndrome ◽

Telomere Length ◽

Scientific Evidence ◽

Telomeric Dna ◽

Biochemical Alterations ◽

The Metabolic Syndrome ◽

Age Related ◽

And Function

A great amount of scientific evidence supports that Oxidative Stress (OxS) can contribute to telomeric attrition and also plays an important role in the development of certain age-related diseases, among them the metabolic syndrome (MetS), which is characterised by clinical and biochemical alterations such as obesity, dyslipidaemia, arterial hypertension, hyperglycaemia, and insulin resistance, all of which are considered as risk factors for type 2 diabetes mellitus (T2DM) and cardiovascular diseases, which are associated in turn with an increase of OxS. In this sense, we review scientific evidence that supports the association between OxS with telomere length (TL) dynamics and the relationship with MetS components in aging. It was analysed whether each MetS component affects the telomere length separately or if they all affect it together. Likewise, this review provides a summary of the structure and function of telomeres and telomerase, the mechanisms of telomeric DNA repair, how telomere length may influence the fate of cells or be linked to inflammation and the development of age-related diseases, and finally, how the lifestyles can affect telomere length.

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TYPE 2 (SUBRETINAL) NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION ASSOCIATED WITH PURE RETICULAR PSEUDODRUSEN PHENOTYPE

Retina ◽

10.1097/iae.0000000000000758 ◽

2016 ◽

Vol 36 (3) ◽

pp. 449-457 ◽

Cited By ~ 14

Author(s):

Jonathan Naysan ◽

Jesse J. Jung ◽

Kunal K. Dansingani ◽

Chandrakumar Balaratnasingam ◽

K. Bailey Freund

Keyword(s):

Macular Degeneration ◽

Age Related Macular Degeneration ◽

Subretinal Neovascularization ◽

Reticular Pseudodrusen ◽

Age Related

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Evaluation of Representative Piping Systems Designed by Implicit Fatigue Concept

Volume 1: Codes and Standards ◽

10.1115/pvp2008-61581 ◽

2008 ◽

Cited By ~ 1

Author(s):

Shin-Beom Choi ◽

Sun-Hye Kim ◽

Yoon-Suk Chang ◽

Jae-Boong Choi ◽

Young-Jin Kim ◽

...

Keyword(s):

Fatigue Life ◽

Nuclear Power ◽

Heat Removal ◽

Environmental Water ◽

Lessons Learned ◽

Metal Fatigue ◽

Aging Effects ◽

Age Related ◽

Piping Systems ◽

Surge Line

NUREG-1801 provides generic aging lessons learned to manage aging effects that may occur during continued operation beyond the design life of nuclear power plant. According to this report, the metal fatigue, among several age-related degradation mechanisms, is identified as one of time-limited aging analysis item. The objective of this paper is to introduce fatigue life evaluation of representative surge line and residual heat removal system piping which was designed by implicit fatigue concept. For the back-fitting evaluation employing explicit fatigue concept, detailed parametric CFD as well as FE analyses results are used. The well-known ASME Section III NB-3600 procedure is adopted for the metal fatigue and NUREG/CR-5704 procedure is further investigated to deal with additional environmental water effects. With regard to the environmental effect evaluation, two types of fatigue life correction factors are considered, such as maximum Fen and individual Fen. As a result, it was proven that a thermal stratification phenomenon is the governing factor in metal fatigue life of the surge line and strain rate is the most important parameter affecting the environmental fatigue life of both piping. The evaluation results will be used as technical bases for continued operation of OPR 1000 plant.

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Associations of cardiovascular diseases and type 2 diabetes with ophthalmic diseases in a population sample over 55 years old

CARDIOVASCULAR THERAPY AND PREVENTION ◽

10.15829/1728-8800-2021-2886 ◽

2021 ◽

Vol 20 (7) ◽

pp. 2886

Author(s):

A. O. Direev ◽

I. V. Munts ◽

E. S. Mazurenko ◽

M. Yu. Shapkina ◽

A. N. Ryabikov ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Diseases ◽

Carotid Atherosclerosis ◽

Population Sample ◽

Age Related Macular Degeneration ◽

Hypertensive Retinopathy ◽

Multivariate Models ◽

Age Related ◽

Ophthalmic Diseases

Aim. To study associations of cardiovascular diseases and type 2 diabetes (T2D) with ophthalmic diseases in a population sample of men and women from middle to old age (Novosibirsk).Material and methods. The population cohort was initially studied in 2003-2005 (n=9360, 45-69 years old, Novosibirsk, the Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE) project). At the second survey (2015-2017) in a random subsample (n=1011), the following ophthalmic diseases were identified: hypertensive retinopathy (HR), diabetic retinopathy (DR), cataract, glaucoma, age-related macular degeneration (AMD), optic disc abnormalities, etc.Results. The prevalence of HR signs in persons with and without hypertension (HTN) was 81 and 46%, respectively (p<0,001). This association persisted regardless of other factors (odds ratio, 2,27 (95% confidence interval: 1,78-4,17). The prevalence of AMD, cataract and DR increased in HTN, but associations were largely explained by metabolic factors in multivariate models. People with T2D more often than without T2D had signs of DR (9,3 vs 0,4%, p<0,001), AMD (22 vs 17%, p=0,042) and glaucoma (14 vs 7%, p=0,001). Associations of T2D with DR and glaucoma persisted regardless of other factors. Individuals with carotid atherosclerosis (CA) were 1,6 times more likely to have HR than those without CA when adjusted for sex, age, and smoking (p=0,013).Conclusion. In the surveyed population sample of mainly elderly people, a number of associations between cardiometabolic and common ophthalmic diseases were revealed. The identified comorbidities may have important therapeutic and prophylactic applications in an aging population.

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Clinical Characteristics and Risk of Diabetic Complications in Data-Driven Clusters Among Type 2 Diabetes

Frontiers in Endocrinology ◽

10.3389/fendo.2021.617628 ◽

2021 ◽

Vol 12 ◽

Author(s):

Lin Xing ◽

Fangyu Peng ◽

Qian Liang ◽

Xiaoshuang Dai ◽

Junli Ren ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Complications ◽

Clinical Characteristics ◽

Chinese Patients ◽

Newly Diagnosed ◽

Medication Treatment ◽

Dipeptidyl Peptidase 4 ◽

Age Related

BackgroundThis study aimed to cluster newly diagnosed patients and patients with long-term diabetes and to explore the clinical characteristics, risk of diabetes complications, and medication treatment related to each cluster.Research Design and MethodsK-means clustering analysis was performed on 1,060 Chinese patients with type 2 diabetes based on five variables (HbA1c, age at diagnosis, BMI, HOMA2-IR, and HOMA2-B). The clinical features, risk of diabetic complications, and the utilization of elven types of medications agents related to each cluster were evaluated with the chi-square test and the Tukey–Kramer method.ResultsFour replicable clusters were identified, severe insulin-resistant diabetes (SIRD), severe insulin-deficient diabetes (SIDD), mild obesity-related diabetes (MOD), and mild age-related diabetes (MARD). In terms of clinical characteristics, there were significant differences in blood pressure, renal function, and lipids among clusters. Furthermore, individuals in SIRD had the highest prevalence of stages 2 and 3 chronic kidney disease (CKD) (57%) and diabetic peripheral neuropathy (DPN) (67%), while individuals in SIDD had the highest risk of diabetic retinopathy (32%), albuminuria (31%) and lower extremity arterial disease (LEAD) (13%). Additionally, the difference in medication treatment of clusters were observed in metformin (p = 0.012), α-glucosidase inhibitor (AGI) (p = 0.006), dipeptidyl peptidase 4 inhibitor (DPP-4) (p = 0.017), glucagon-like peptide-1 (GLP-1) (p <0.001), insulin (p <0.001), and statins (p = 0.006).ConclusionsThe newly diagnosed patients and patients with long-term diabetes can be consistently clustered into featured clusters. Each cluster had significantly different patient characteristics, risk of diabetic complications, and medication treatment.

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Hypertension and Micro-Vascular Complications Among Type 2 Dm Adult Patients in Mukalla, Yemen

Journal of Clinical Research and Reports ◽

10.31579/2690-1919/056 ◽

2020 ◽

Vol 3 (5) ◽

pp. 01-04

Author(s):

Abdullah Ghouth

Keyword(s):

Care Center ◽

Vascular Complications ◽

Diabetic Patients ◽

Type 2 Diabetic Patients ◽

Cross Sectional ◽

Health Care Center ◽

Age Related ◽

Significant Difference ◽

High Prevalence

The Background and Purpose: to assess the prevalence of hypertension and micro-vascular complications among type 2 diabetic patients registered in primary health care center in Mukalla city at eastern Yemen. Methods: A Cross-sectional study was conducted in a randomly selected eligible patients from the diabetic registry of the AL Noor Charity Center (ACC), Mukalla city in Yemen. Results: Prevalence of hypertension in the T2DM patients were 46.7% (56/120). Retinopathy is the most micro-vascular complications among the adults having T2DM (73/120, 60.8%) while nephropathy is the least prevalence (13/120, 10.8%), prevalence of neuropathy was 49.2% (59/120). a high prevalence of retinopathy in males (66%) than females (55.7%) and a high prevalence of neuropathy in male adults (52.2%) than females (46%).No statistical significant difference were exit related to gender for any studied complications. Similar findings were observed regarding age related variations. Conclusion: A high prevalence of hypertension, retinopathy and neuropathy were reported among T2DM patients in Mukalla. Adopting effective and safe treatment strategies are highly recommended to prevent premature death and complications due to DM.

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