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Age (Dordrecht, Netherlands) Feb 2016Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups.... (Review)
Review
Obesity has become a major public health problem. Given the current increase in life expectancy, the prevalence of obesity also raises steadily among older age groups. The increase in life expectancy is often accompanied with additional years of susceptibility to chronic ill health associated with obesity in the elderly. Both obesity and ageing are conditions leading to serious health problems and increased risk for disease and death. Ageing is associated with an increase in abdominal obesity, a major contributor to insulin resistance and the metabolic syndrome. Obesity in the elderly is thus a serious concern and comprehension of the key mechanisms of ageing and age-related diseases has become a necessary matter. Here, we aimed to identify similarities underlying mechanisms related to both obesity and ageing. We bring together evidence that age-related changes in body fat distribution and metabolism might be key factors of a vicious cycle that can accelerate the ageing process and onset of age-related diseases.
Topics: Aged; Aging; Body Composition; Global Health; Humans; Insulin Resistance; Life Expectancy; Obesity; Prevalence; Risk Factors
PubMed: 26846415
DOI: 10.1007/s11357-016-9884-3 -
Age (Dordrecht, Netherlands) Aug 2015Many, even healthy, older people fail to adequately regulate food intake and experience loss of weight. Aging-associated changes in the regulation of appetite and the... (Review)
Review
Many, even healthy, older people fail to adequately regulate food intake and experience loss of weight. Aging-associated changes in the regulation of appetite and the lack of hunger have been termed as the anorexia of aging. The etiology of the anorexia of aging is multi-factorial and includes a combination of physiological changes associated with aging (decline in smell and taste, reduced central and peripheral drive to eat, delayed gastric emptying), pathological conditions (depression, dementia, somatic diseases, medications and iatrogenic interventions, oral-health status), and social factors (poverty, loneliness). However, exact mechanisms of the anorexia of aging remain to be elucidated. Many neurobiological mechanisms may be secondary to age-related changes in body composition and not associated with anorexia per se. Therefore, further studies on pathophysiological mechanisms of the anorexia of aging should employ accurate measurement of body fat and lean mass. The anorexia of aging is associated with protein-energy malnutrition, sarcopenia, frailty, functional deterioration, morbidity, and mortality. Since this symptom can lead to dramatic consequences, early identification and effective interventions are needed. One of the most important goals in the geriatric care is to optimize nutritional status of the elderly.
Topics: Aging; Anorexia; Appetite; Eating; Gastrointestinal Absorption; Gastrointestinal Motility; Humans
PubMed: 26232135
DOI: 10.1007/s11357-015-9821-x -
Age (Dordrecht, Netherlands) Mar 2010In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in... (Review)
Review
In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.
Topics: Aging; Animals; Biomarkers; Cognition Disorders; Dehydroepiandrosterone Sulfate; Humans; Models, Animal; Rodentia
PubMed: 19711196
DOI: 10.1007/s11357-009-9113-4 -
Age (Dordrecht, Netherlands) Aug 2015The sirtuins comprise a highly conserved family proteins present in virtually all species from bacteria to mammals. Sirtuins are members of the highly conserved class... (Review)
Review
The sirtuins comprise a highly conserved family proteins present in virtually all species from bacteria to mammals. Sirtuins are members of the highly conserved class III histone deacetylases, and seven sirtuin genes (sirtuins 1-7) have been identified and characterized in mammals. Sirtuin activity is linked to metabolic control, apoptosis, cell survival, development, inflammation, and healthy aging. In this review, we summarize and discuss the potential mutual relations between each sirtuin and cardiovascular health and the impact of sirtuins on oxidative stress and so age-related cardiovascular disorders, underlining the possibility that sirtuins will be novel targets to contrast cardiovascular risks induced by aging.
Topics: Aging; Animals; Cardiovascular Diseases; Humans; Oxidative Stress; Risk Factors; Sirtuins
PubMed: 26099749
DOI: 10.1007/s11357-015-9804-y -
Age (Dordrecht, Netherlands) Dec 2010As life expectancy continually increases, it is imperative to identify determinants of survival to the extreme end of the lifespan and more importantly to identify...
As life expectancy continually increases, it is imperative to identify determinants of survival to the extreme end of the lifespan and more importantly to identify factors that increase the chance of survival free of major morbidities. As such, the current study assessed 45 common disease factors as predictors of survival and morbidity-free survival to age 85 years. Within the Rotterdam Study, a population-based cohort, we evaluated morbidity-free participants who were able to attain age 85 within the study duration (n = 2,008). Risk factors were assessed at baseline (1990-1993), and mortality and morbidities were then collected continuously until mortality or the occurrence of their 85th birthday (average time of 7.9 years). Risk factors included demographic and lifestyle variables, health and morbidity indicators and physiological makers. Major morbidities examined included dementia, cancer, cerebrovascular accident, heart failure and myocardial infarction. Logistic regression analyses demonstrated that many of the variables were independently predictive for survival and for morbidity-free ageing to 85 years. These included being female, absence of left ventricular abnormalities, stable body weight, unimpaired instrumental activities of daily living, lower C-RP levels and higher levels of femoral neck bone mineral density and albumin. Relative to non-survival, predictors were stronger for morbidity-free survival than for total survival or survival with morbidity. This suggests that lifespan and healthy survival to older age can be relatively well predicted. Understanding predictors of a long and healthy lifespan is vital for developing primary and secondary preventions to help improve the quality of life of older adults and for reducing the financial burden of the rapidly escalating ageing population.
Topics: Aged; Aged, 80 and over; Aging; Albumins; Biomarkers; Bone Density; C-Reactive Protein; Dementia; Disease-Free Survival; Female; Femur Neck; Heart Failure; Humans; Life Expectancy; Life Style; Logistic Models; Longevity; Male; Middle Aged; Myocardial Infarction; Neoplasms; Netherlands; Predictive Value of Tests; Prospective Studies; Quality of Life; Radiography; Risk Factors; Stroke; Survival Rate
PubMed: 20514522
DOI: 10.1007/s11357-010-9154-8 -
Age (Dordrecht, Netherlands) 2014Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune... (Review)
Review
Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.
Topics: Aging; Animals; Autoimmune Diseases; Bacterial Infections; Female; Humans; Immune Tolerance; Immunity, Cellular; Immunity, Innate; Immunosuppression Therapy; Male; Mice; Myeloid Cells; Neoplasms; Virus Diseases
PubMed: 25399072
DOI: 10.1007/s11357-014-9729-x -
Age (Dordrecht, Netherlands) Jun 2014Advanced age is characterized by increased incidence of many chronic, noninfectious diseases that impair the quality of living of the elderly and pose a major burden on... (Review)
Review
Advanced age is characterized by increased incidence of many chronic, noninfectious diseases that impair the quality of living of the elderly and pose a major burden on the healthcare systems of developed countries. These diseases are characterized by impaired or altered function at the tissue and cellular level, which is a hallmark of the aging process. Age-related impairments are likely due to loss of homeostasis at the cellular level, which leads to the accumulation of dysfunctional organelles and damaged macromolecules, such as proteins, lipids, and nucleic acids. Intriguingly, aging and age-related diseases can be delayed by modulating nutrient signaling pathways converging on the target of rapamycin (TOR) kinase, either by genetic or dietary intervention. TOR signaling influences aging through several potential mechanisms, such as autophagy, a degradation pathway that clears the dysfunctional organelles and damaged macromolecules that accumulate with aging. Autophagy substrates are targeted for degradation by associating with p62/SQSTM1, a multidomain protein that interacts with the autophagy machinery. p62/SQSTM1 is involved in several cellular processes, and its loss has been linked to accelerated aging and to age-related pathologies. In this review, we describe p62/SQSTM1, its role in autophagy and in signaling pathways, and its emerging role in aging and age-associated pathologies. Finally, we propose p62/SQSTM1 as a novel target for aging studies and age-extending interventions.
Topics: Adaptor Proteins, Signal Transducing; Aging; Autophagy; DNA; Gene Expression Regulation, Developmental; Humans; Immediate-Early Proteins; Sequestosome-1 Protein; Signal Transduction
PubMed: 24557832
DOI: 10.1007/s11357-014-9626-3 -
Age (Dordrecht, Netherlands) Jun 2013Ageing is accompanied by alterations to T-cell immunity and also by a low-grade chronic inflammatory state termed inflammaging. The significance of these phenomena is... (Review)
Review
Ageing is accompanied by alterations to T-cell immunity and also by a low-grade chronic inflammatory state termed inflammaging. The significance of these phenomena is highlighted by their being predictors of earlier mortality. We have recently published that the proinflammatory cytokine TNFα is a strong inducer of CD4(+) T-cell senescence and T-cell differentiation, adding to the growing body of literature implicating proinflammatory molecules in mediating these critical age-related T-cell alterations. Moreover, the inflammatory process is also being increasingly implicated in the pathogenesis of many common and severe age-related diseases, including cancer, cardiovascular diseases and type 2 diabetes. Furthermore, major age-related risk factors for poor health, such as obesity, stress and smoking, are also associated with an upregulation in systemic inflammatory markers. We propose the idea that the ensuing inflammatory response to influenza infection propagates cardiovascular diseases and constitutes a major cause of influenza-related mortality. While inflammation is not a negative phenomenon per se, this age-related dysregulation of inflammatory responses may play crucial roles driving age-related pathologies, T-cell immunosenescence and CMV reactivation, thereby underpinning key features of the ageing process.
Topics: Aging; Animals; Cytokines; Humans; Inflammation; Longevity; T-Lymphocytes
PubMed: 22252437
DOI: 10.1007/s11357-012-9381-2 -
Age (Dordrecht, Netherlands) Mar 2009Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-beta, hypoxia-induced factor (HIF), and the...
Many age-related diseases are associated with, and may be promoted by, cardiac fibrosis. Transforming growth factor (TGF)-beta, hypoxia-induced factor (HIF), and the matrix metalloproteinase (MMP) system have been implicated in fibrogenesis. Thus, we investigated whether age is related to these systems and to atrial fibrosis. Right atrial appendages (RAA) obtained during heart surgery (n = 115) were grouped according to patients' age (<50 years, 51-60 years, 61-70 years, or >70 years). Echocardiographic ejection fractions (EF) and fibrosis using Sirius-red-stained histological sections were determined. TGF-beta was determined by quantitative RT-PCR and hypoxia-related factors [HIF1 alpha, the vascular endothelial growth factor (VEGF)-receptor, CD34 (a surrogate marker for microvessel density), the factor inhibiting HIF (FIH), and prolyl hydroxylase 3 (PHD 3)] were detected by immunostaining. MMP-2 and -9 activity were determined zymographically, and mRNA levels of their common tissue inhibitor TIMP-1 were determined by RT-PCR. Younger patients (<50 years) had significantly less fibrosis (10.1% +/- 4.4% vs 16.6% +/- 8.3%) than older individuals (>70 years). While HIF1 alpha, FIH, the VEGF-receptor, and CD34 were significantly elevated in the young, TGF-beta and PHD3 were suppressed in these patients. MMP-2 and -9 activity was found to be higher while TIMP-1 levels were lower in older patients. Statistical analysis proved age to be the only factor influencing fibrogenesis. With increasing age, RAAs develop significantly more fibrosis. An increase of fibrotic and decrease of hypoxic signalling and microvessel density, coupled with differential expression of MMPs and TIMP-1 favouring fibrosis may have helped promote atrial fibrogenesis.
PubMed: 19234766
DOI: 10.1007/s11357-008-9077-9 -
Age (Dordrecht, Netherlands) Dec 2016Age at menarche (AM) and age at natural menopause (ANM) are complex traits with a high heritability. Abnormal timing of menarche or menopause is associated with a... (Comparative Study)
Comparative Study
Age at menarche (AM) and age at natural menopause (ANM) are complex traits with a high heritability. Abnormal timing of menarche or menopause is associated with a reduced span of fertility and risk for several age-related diseases including breast, endometrial and ovarian cancer, cardiovascular disease, and osteoporosis. To identify novel genetic loci for AM or ANM in East Asian women and to replicate previously identified loci primarily in women of European ancestry by genome-wide association studies (GWASs), we conducted a two-stage GWAS. Stage I aimed to discover promising novel AM and ANM loci using GWAS data of 8073 women from Shanghai, China. The Stage II replication study used the data from another Chinese GWAS (n = 1230 for AM and n = 1458 for ANM), a Korean GWAS (n = 4215 for AM and n = 1739 for ANM), and de novo genotyping of 2877 additional Chinese women. Previous GWAS-identified loci for AM and ANM were also evaluated. We identified two suggestive menarcheal age loci tagged by rs79195475 at 10q21.3 (beta = -0.118 years, P = 3.4 × 10) and rs1023935 at 4p15.1 (beta = -0.145 years, P = 4.9 × 10) and one menopausal age locus tagged by rs3818134 at 22q12.2 (beta = -0.276 years, P = 8.8 × 10). These suggestive loci warrant a further validation in independent populations. Although limited by low statistical power, we replicated 19 of the 98 menarche loci and 5 of the 20 menopause loci previously identified in women of European ancestry in East Asian women, suggesting a shared genetic architecture for these two traits across populations.
Topics: Age Factors; Aged; Asian People; China; Cohort Studies; Female; Genetic Loci; Genome-Wide Association Study; Genotype; Humans; Korea; Linear Models; Menarche; Menopause; Middle Aged; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 27629107
DOI: 10.1007/s11357-016-9939-5