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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) Oct 2012The cognitive decline associated with normal aging was long believed to be due primarily to decreased synaptic density and neuron loss. Recent studies in both humans and... (Review)
Review
The cognitive decline associated with normal aging was long believed to be due primarily to decreased synaptic density and neuron loss. Recent studies in both humans and non-human primates have challenged this idea, pointing instead to disturbances in white matter (WM) including myelin damage. Here, we review both cross-sectional and longitudinal studies in humans and non-human primates that collectively support the hypothesis that WM disturbances increase with age starting at middle age in humans, that these disturbances contribute to age-related cognitive decline, and that age-related WM changes may occur as a result of free radical damage, degenerative changes in cells in the oligodendrocyte lineage, and changes in microenvironments within WM.
Topics: Aging; Animals; Brain; Cognition Disorders; Humans; Magnetic Resonance Imaging; Nerve Fibers, Myelinated; Primates
PubMed: 22203458
DOI: 10.1007/s11357-011-9357-7 -
Age (Dordrecht, Netherlands) Dec 2006
PubMed: 22253497
DOI: 10.1007/s11357-006-9025-5 -
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 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 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) 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) Oct 2012Many environmental conditions show rhythmic changes across the 24-h day; these include changes in light intensity, ambient temperature, food availability, and presence... (Review)
Review
Many environmental conditions show rhythmic changes across the 24-h day; these include changes in light intensity, ambient temperature, food availability, and presence or absence of predators. Consequently, many organisms have developed corresponding adaptations, which ensure that specific physiological and behavioral events occur at an appropriate time of the day. In mammals, the underlying mechanism responsible for synchronizing internal biochemical processes with circadian environmental cues has been well studied and is thought to comprise three major components: (1) photoreception by the retina and transmission of neural signals along the retinohypothalamic tract, (2) integration of photoperiodic information with an internal reference circadian pacemaker located in the suprachiasmatic nucleus, and (3) dissemination of circadian information to target organs, via the autonomic nervous system and through humoral pathways. Given the importance that neuroendocrine rhythms play in coordinating normal circadian physiology and behavior, it is plausible that their perturbation during aging contributes to the etiology of age-related pathologies. This mini-review highlights some of the most dramatic rhythmic neuroendocrine changes that occur in primates during aging, focusing primarily on data from the male rhesus macaques (Macaca mulatta). In addition to the age-associated attenuation of hormone levels and reduction of humoral circadian signaling, there are also significant age-related changes in intracrine processing enzymes and hormone receptors which may further affect the functional efficacy of these hormones. Rhesus macaques, like humans, are large diurnal primates and show many of the same physiological and behavioral circadian changes during aging. Consequently, they represent an ideal translational animal model in which to study the causes and consequences of age-associated internal circadian disruption and in which to evaluate novel therapies.
Topics: Aging; Animals; Brain; Circadian Rhythm; Macaca mulatta; Neurosecretory Systems
PubMed: 22198672
DOI: 10.1007/s11357-011-9352-z -
Age (Dordrecht, Netherlands) Jun 2006
PubMed: 19943134
DOI: 10.1007/s11357-006-9012-x -
Age (Dordrecht, Netherlands) Jun 2006Two mutant mouse models of longevity in which the loss of only one copy of the gene leads to a significantly increased lifespan have recently been described: Igf1r (+/-)...
Two mutant mouse models of longevity in which the loss of only one copy of the gene leads to a significantly increased lifespan have recently been described: Igf1r (+/-) and mclk1 (+/-). Igf1r encodes a transmembrane receptor kinase for the insulin-like growth factor-1, and mclk1 encodes a hydroxylase that is necessary for the biosynthesis of ubiquinone. Interestingly, the motivation for testing the longevity of both of these mutants came from observations in the nematode Caenorhabditis elegans. IGF-1R protein is homologous to DAF-2 and mCLK1 is the mouse orthologue of the C. elegans enzyme CLK-1. In worms, the homozygous inactivation of both of these longevity genes is viable and no dominant mutations are known. In addition to aging slowly, old mclk1 (+/-) mice were found to undergo loss-of-heterozygosity at the mclk1 locus, which results in clones of mclk1 (-/-) cells in the liver, presumably because mclk1 (-/-) cells can outcompete mclk1 (+/-) cells under certain conditions. We will discuss how these observations suggest novel directions of research, but also call for some caution in the interpretation of past and future results.
PubMed: 19943141
DOI: 10.1007/s11357-006-9006-8