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Adiponectin levels according to age. a, Adiponectin levels, adjusted for sex and body mass index (BMI) in long-lived probands and controls. This group represents a continuous age group of unrelated individuals from 51 to 106 years of age. b, Adiponectin levels, adjusted for BMI in long-lived probands and controls stratified by sex. c, Adiponectin levels, adjusted for BMI in offspring of long-lived probands stratified by sex. *p ¼ .05, **p ¼ .01 for comparison to the ,65-year-old group. # p , .05 for comparison to the 66-to 75-year-old group. z p , .05 for comparison to the 76-to 85-year-old group. § p , .01 for comparison to females within stratified group.
Source publication
Although caloric restriction in numerous models extends life, longevity in humans is suggested to be limited by the increased
prevalence of obesity. Adiponectin, a fat-derived peptide, has a protective role against age-related disease, and thus is
an excellent candidate gene for longevity. We studied adiponectin levels in centenarians (n = 118), th...
Contexts in source publication
Context 1
... of adiponectin levels with other variables were estimated using regression on an indicator variable for group, stratifying for age, sex, and BMI. In defining strata for age, cut points of 65, 70, 75, 80, and 85 years were used ( Figure 1). Spearman correlations for BMI, % fat, and age were adjusted for age and sex (except age). Spearman correlations for metabolic syndrome-associated traits (i.e., blood pressure, HDL, LDL, triglycerides, glucose, waist circumference, and HDL and LDL particle sizes) were adjusted for age, sex, and BMI (Table ...
Context 2
... phenotypic characteristics of exceptionally long-lived probands, their offspring, and unrelated controls are shown in Table 1. Adiponectin levels are known to be associated with age and BMI (a surrogate for body fat), and these relationships held in our sample ( Figure 1 and Table 2). As previously described (31,32), women had significantly higher adiponectin levels than did men in the combined sample (15.6 6 0.49 vs 11.6 6 0.58 lg/mL; p , .0001, adjusted for age at recruitment and BMI. Furthermore, adiponectin levels were correlated with some serum lipid levels (Table 2), for example, Spearman correlation coefficients for triglycerides and HDL with adiponectin levels were À0.19 (p ¼ .0005) and 0.23 (p , .0001), respectively. Lipoprotein particle sizes were positively correlated, whereas waist circumference was negatively correlated with adiponectin levels (Table 2). Glucose, LDL levels, and blood pressure showed no significant correlation with adiponectin ...
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Citations
... According to vast majority of reports, adiponectin has been exhibited to have protective effect on vascular functions and thus has negative relationship with blood pressure, against incidence of obesity-hypertension [21,140,141]. But the contrary opinion holds that, in different subject groups, the relationships between the adiponectin and blood pressure are various, with positive and non-correlation existing [24,[142][143][144]. The preclinical expriments, longitudinal studies and clinical trials have reported inconsistent outcomes regarding the antihypertensive effects of adiponectin [11,13,[25][26][27][28][29]145]. ...
Background
Obesity and hypertension are major risk factors for cardiovascular diseases that affect millions of people worldwide. Both conditions are associated with chronic low-grade inflammation, which is mediated by adipokines such as adiponectin. Adiponectin is the most abundant adipokine that has a beneficial impact on metabolic and vascular biology, while high serum concentrations are associated with some syndromes. This “adiponectin paradox” still needs to be clarified in obesity-associated hypertension. The aim of this study was to investigate how adiponectin affects blood pressure, inflammation, and metabolic function in obesity hypertension using a Chinese adult case-control study.
Methods
A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Adiponectin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS.
Results
Serum adiponectin levels in the| normal healthy group (NH group) were significantly higher than those in the newly diagnosed untreated just-obesity group (JO group), and negatively correlated with the visceral adiposity index. With multiple linear egression analysis, it was found that, for serum adiponectin, gender, serum albumin (ALB), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDLC) were the significant independent correlates, and for SB, age and HDLC were the significant independent correlates, and for DB, alkaline phosphatase (ALP) was the significant independent correlate. The other variables did not reach significance in the model.
Conclusions
Our study reveals that adiponectin’s role in obesity-hypertension is multifaceted and is influenced by the systemic metabolic homeostasis signaling axis. In obesity-related hypertension, compensatory effects, adiponectin resistance, and reduced adiponectin clearance from impaired kidneys and liver all contribute to the “adiponectin paradox”.
... Аналогичные данные были опубликованы Atzmon G. с соавт. -они также подтвердили у 118 долгожителей более благоприятный метаболический профиль: в популяции были повышены уровни адипонектина, обратно коррелировавшие с ИМТ, окружностью талии и процентом жира в организме, и имевшие положительную связь с уровнем ЛПВП [20]. ...
Adipose tissue is an active endocrine organ that regulates energy homeostasis throughout the body by releasing hundreds of biologically active substances called adipokines. Dysregulation of adipokines is a key feature of insulin resistance with the development of metabolic syndrome and type 2 diabetes mellitus, which is an age-dependent pathology. In turn, dysregulation of adipokines and insulin resistance are associated with the development of metabolic deficiency and senile asthenia syndrome in older age groups. Previous studies have shown that the absence of insulin resistance and low prevalence of diabetes among centenarians are metabolic prerequisites for increased lifespan, suggesting a possible role for adipokine homeostasis in healthy longevity. Among numerous adipokines, adiponectin is considered a protective factor, showing a negative correlation with major metabolic disorders associated with age and obesity, and a positive association with life expectancy and insulin sensitivity among centenarians. Despite all the apparent protective effects of adiponectin, large-scale epidemiological studies have revealed the opposite aspect of adiponectin as a predictor of all-cause mortality and cardiovascular disease in patients with heart failure as well as kidney disease. In this review, the clinical significance of adiponectin is considered in centenarians from the point of view of the development of the main geriatric syndrome - senile asthenia, as well as cardiovascular risk and mortality.
... Furthermore, aging is associated with the redistribution of adipose tissue, involving the transfer of fat from subcutaneous depots to visceral depots (23). Individuals with higher levels of adiponectin, expressed in adipose tissue, are reported to have extended lifespans (24). Some interventions aimed at delaying aging, such as calorie restriction, gene mutations (such as insulinlike growth factor 1 receptor (IGF-1R)), and pharmaceuticals (such as metformin), have demonstrated the ability to impact lipid metabolism (25-27). ...
Objective
The Klotho protein is a well-documented anti-aging protein known for its diverse biological functions. Hyperlipidemia is an established independent risk factor for various chronic diseases. However, there is limited understanding of the connection between Klotho and hyperlipidemia. The aim was to assess the association between serum Klotho levels and hyperlipidemia among adults.
Methods
The study included 11,618 individuals from the NHANES database from 2006 to 2017. Hyperlipidemia was diagnosed following the National Cholesterol Education Program guidelines. Serum Klotho concentration was measured by an enzyme-linked immunosorbent assay kit, and the association between Klotho and hyperlipidemia was assessed by a multivariable logistic regression model. Fitted smoothing curves and threshold-effect analysis were employed to describe nonlinear relationships.
Results
In our multiple logistic regression models, serum Klotho concentration was significantly associated with hyperlipidemia after adjusting for comprehensive confounders (per SD increment odds ratio (OR): 0.91; 95% confidence interval (CI): 0.86–0.97). Compared to individuals in the lowest Klotho quartile, those in the highest quartile exhibited a substantially decreased prevalence of hyperlipidemia (OR: 0.72; 95% CI: 0.58–0.90). Using a two-segment logistic regression model, we identified a U-shaped relationship between serum Klotho concentration and hyperlipidemia, with an inflection point at 1,365.5 pg/mL. Subgroup analysis did not reveal any potential moderating effects.
Conclusion
This study revealed an inverse relationship between Klotho levels and hyperlipidemia. Further investigation is warranted to explore the underlying mechanism between serum Klotho and hyperlipidemia.
... Given that the liver is the source of SHBG, it is important to consider whether the two opposing responses to ageing and weight gain are due to modifications in the liver's metabolic state (Kaufman et al., 2019). Increase in SHBG levels as a result of age in men are not well understood, however, adiponectin, an anti-inflammatory cytokine, has been demonstrated to enhance the generation of SHBG in cultured human liver cells by stimulating AMP-activated protein kinase, lowering lipid content as well as stimulating hepatocyte nuclear factor (HNF), may be one of the explanations for this (Atzmon et al., 2008;Udomsinprasert et al., 2018;Nguyen, 2020). Fig. 2 shows a schematic of the proposed molecular mechanisms that contributes to obesity-associated reduction of the synthesis of hepatic SHBG. ...
Ageing is a natural process with physiological changes in different body parts and has been associated with decreased reproductive capacity. Factors such as imbalance in the antioxidant defence system, vascular diseases, diabetes mellitus, accessory reproductive glands infection, obesity as well as buildup of toxic substances play a role in age-related male reproductive malfunction. Age is inversely proportional to volume of semen, sperm count, sperm progressive motility, sperm viability, normal sperm morphology. The observed negative correlation between ageing and semen indices contributes to male infertility and reproductive decline. Normal levels of ROS, plays crucial role in facilitating sperm function, such as capacitation, hyper-activation, acrosome reaction as well as sperm-oocyte fusion; however, a substantial elevation in the endogenous level of ROS, especially in reproductive tissues, usually instigates destruction of sperm cells and heightened male infertility. Contrarily, antioxidants, such as vitamins C and E, beta-carotene, and micronutrients like zinc and folate, have been found by researchers to facilitate normal semen quality and male reproductive function. Furthermore, the role of hormonal imbalance as a result of the compromised hypothalamic-pituitary-gonadal axis, Sertoli and Leydig cells disorder, and nitric oxide-medicated erectile dysfunction during ageing cannot be undermined.
... Inflammaging may have a role in the decline of the AMPK activity. The ability to respond to oxidative stress with the activation of Nrf2 signaling and expression of its target antioxidant genes declines with age [128]. Adiponectin has a protective role against age-related diseases, and thus is an excellent candidate gene for longevity [129]. ...
Immortal, infinitely reproducing organisms, aka Darwinian demons, claiming the majority of resources, would severely undermine the fitness of offspring. Evolution co-selected fertility and longevity, linking births to deaths and creating various trait correlations, e.g., the fast-slow continuum of life history strategies. Importantly, these correlations and trade-offs are modulated by resource availability and acquisition. The ecological conditions-dependent semelparity-iteroparity plasticity and continuum highlights the programmed nature of both reproductive modes and reproduction-related death pathways. Parental effects, as transgenerational indirect genetic effects, and eco-evolutionary feedback underlie the aging-related action of multilevel selection. Aging trajectories are determined by energy budgets, reproductive activity and stress responses. Evolution "appointed" the germline cells, the prospective individuals of the next generation, as guardians of limited resources and mediators of population regulation. In this capacity, beginning at reproductive maturity, signals of germline cells more or less gradually degenerate parental immune competence, undermine stress response pathways and proteostasis, and derange mitochondrial energy homeostasis. Moreover, the reproductive activity of organisms limits itself, restricting the number of offspring depending on ecological births-deaths balance. The soma is not defenseless. Longevity is correlated and co-selected with somatic stress response capacity. Aging is a survival program of the soma, resisting germline-imposed death. Throughout phylogeny, metabolically stressed organisms downregulate metabolic rate by means of insulin resistance and store rather than use nutrients. In this legacy, aging organisms activate the metabolic stress program and inflammatory defense. The somatic hypometabolic-hypoxic reprogramming adjusts oxygen supply to metabolic demands. The aging organism downregulates vasorelaxant gasotransmitters, while atrial natriuretic peptide becomes resistant. On the other hand, a variety of vasopressor agents are upregulated including type 5 phosphodiesterases. This results in increased vascular tone, reduced tissue perfusion, tissue hypoxia, and, eventually, hypertension and atherosclerosis. However, the survival factors are incapacitated during the course of aging so that the soma is caught in a dead-end trap.
... In humans, adiponectin/ADIPOQ signaling protects against metabolic diseases [42]. Moreover, adiponectin serum levels are higher in exceptionally long-lived humans when compared to non-long-lived individuals [43]. Adipoq null mice have a slightly decreased lifespan and manifest premature metabolic dysfunction, while mice overexpressing Adipoq have a prolonged health span [44]. ...
Aging causes alterations in body composition. Specifically, visceral fat mass increases with age and is associated with age-related diseases. The pathogenic potential of visceral fat accumulation has been associated with its anatomical location and metabolic activity. Visceral fat may control systemic metabolism by secreting molecules that act in distal tissues, mainly the liver, through the portal vein. Currently, little is known about age-related changes in visceral fat in humans. Aiming to identify molecular and cellular changes occurring with aging in the visceral fat of humans, we analyzed publicly available transcriptomic data of 355 omentum samples from the Genotype-Tissue Expression portal (GTEx) of 20–79-year-old males and females. We identified the functional enrichment of genes associated with aging, inferred age-related changes in visceral fat cellularity by deconvolution analysis, profiled the senescence-associated secretory phenotype of visceral adipose tissue, and predicted the connectivity of the age-induced visceral fat secretome with the liver. We demonstrate that age induces alterations in visceral fat cellularity, synchronous to changes in metabolic pathways and a shift toward a pro-inflammatory secretory phenotype. Furthermore, our approach identified candidates such as ADIPOQ-ADIPOR1/ADIPOR2, FCN2-LPR1, and TF-TFR2 to mediate visceral fat-liver crosstalk in the context of aging. These findings cast light on how alterations in visceral fat with aging contribute to liver dysfunction and age-related disease etiology.
... In humans and rodents, lower levels of adiponectin are associated with obesity, insulin resistance and T2DM (Hotta et al. 2000;Havel 2002). Centenarians have higher levels of adiponectin and this may be associated with longevity (Arai et al. , 2019Atzmon et al. 2008;Kizer et al. 2010;Arai & Nobuyoshi 2012;Gulcelik et al. 2013). Adiponectin levels in the offspring of centenarians were higher (following adjustment for age, sex, and BMI) compared to controls (p = .02), ...
... suggesting that inherited factors play a role in determining adiponectin levels. Over-representation of two common variants in adiponectin gene (ADIPOQ) in male long-lived individuals combined with their independent association with elevated plasma adiponectin levels (in men and women) suggests that their presence may promote increased lifespan through the regulation of adiponectin production and/or secretion (Atzmon et al. 2008). ...
... Adiponectin is a serum protein, expressed and secreted exclusively by adipose tissue that plays a protective role against insulin resistance (Combs et al. 2001;Atzmon et al. 2008) and atherosclerosis (Ouchi et al. 1999;Okamoto et al. 2000;Kubota et al. 2002;Shimada et al. 2004) in humans, and protects the heart from ischemia-reperfusion injury in an animal model (Shibata et al. 2005). Adiponectin exerts its favorable effects on insulin sensitivity in vivo through a decrease in hepatic glucose production (Combs et al. 2001). ...
... Sebastiani et al. (2016b) assessed 38 age-related circulating biomarkers in ~ 5 ,000 healthy, older adults of the long-life family study, aged 25-110 years, and 34 biomarkers had a statistically significant association with age at assessment, including adiponectin that showed a high correlation coefficient with age (r= 0.3178, p < 0.001). Atzmon et al. (2008) studied adiponectin levels in centenarians, their offspring, and a cohort of unrelated participants ൏ 9 5 y e a r s . Adiponectin levels were significantly greater in participants older than 95 years (p = .01), ...
... These cytokines suppress the production of adiponectin. These processes may account for the reduced blood adiponectin expression observed in clinical practice among individuals with obesity and type 2 diabetes [63]. Recent research has demonstrated that adiponectin secretion follows a circadian cycle, with peak production occurring during the day. ...
... Adiponectin is a key protein produced by adipose tissue and plays an important role in protecting against insulin resistance, diabetes, atherosclerosis and other age-related diseases [53]. Some research, looking at the plasma adiponectin levels in centenarians and their offspring, suggest that elevated plasma adiponectin levels may promote increased longevity [53]. ...
... Adiponectin is a key protein produced by adipose tissue and plays an important role in protecting against insulin resistance, diabetes, atherosclerosis and other age-related diseases [53]. Some research, looking at the plasma adiponectin levels in centenarians and their offspring, suggest that elevated plasma adiponectin levels may promote increased longevity [53]. Cold exposure in air or water seems to increase the production of adiponectin in adipose tissue through the process of shivering and non-shivering thermogenesis [54] and could, as such, be seen as a positive health effect. ...
... As discussed earlier, regular cold-water swimming may have an impact on fat loss in men [55]. The physiological reasons explaining this are not fully understood, although adiponectin secretion by nonshivering thermogenesis may contribute to this [53]. If regular winter swimming leads to increased levels of plasma adiponectin, it would be expected to have a positive impact on insulin resistance, diabetes, atherosclerosis and other age-related diseases. ...
This review is based on a multiple database survey on published literature to determine the effects on health following voluntary exposure to cold-water immersion (CWI) in humans. After a filtering process 104 studies were regarded relevant. Many studies demonstrated significant effects of CWI on various physiological and biochemical parameters. Although some studies were based on established winter swimmers, many were performed on subjects with no previous winter swimming experience or in subjects not involving cold-water swimming, for example, CWI as a post-exercise treatment. Clear conclusions from most studies were hampered by the fact that they were carried out in small groups, often of one gender and with differences in exposure temperature and salt composition of the water. CWI seems to reduce and/or transform body adipose tissue, as well as reduce insulin resistance and improve insulin sensitivity. This may have a protective effect against cardiovascular, obesity and other metabolic diseases and could have prophylactic health effects. Whether winter swimmers as a group are naturally healthier is unclear. Some of the studies indicate that voluntary exposure to cold water has some beneficial health effects. However, without further conclusive studies, the topic will continue to be a subject of debate.
