High plasma adiponectin levels are associated with frailty in a general old‐old population: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Nagasawa, Motonori; Takami, Yoichi; Akasaka, Hiroshi; Kabayama, Mai; Maeda, Satomi; Yokoyama, Serina; Fujimoto, Taku; Nozato, Yoichi; Imaizumi, Yuki; Takeda, Masao; Itoh, Noriyuki; Takeya, Yasushi; Yamamoto, Kōichi; Sugimoto, Ken; Nakagawa, Toshio; Masui, Yukie; Arai, Yasumichi; Ishizaki, Tatsuro; Ikebe, Kazunori; Gondo, Yasuyuki; Kamide, Kei; Rakugi, Hiromi

doi:10.1111/ggi.13258

Cited by 27 publications

(23 citation statements)

References 31 publications

(54 reference statements)

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“…It was reported that elevated circulating APN levels were an independent markers of both myocardial infarction (MI) and all-cause mortality in male patients undergoing coronary angiography 37 . Such inverse correlation with circulating APN levels has been also reported on muscle weakness in elderly people 31,32 , muscle mass and strength in elderly heart failure patients 33 . Here we have revealed that high circulating APN levels in mice were not inhibitory but promotive for muscle regeneration at least under high angiotensin II levels, suggesting that above mentioned higher circulating APN in elderly patients especially with heart failure may not be causative for their associated muscle weakness and loss of muscle mass.…”

Section: Discussionsupporting

confidence: 62%

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Adiponectin promotes muscle regeneration through binding to T-cadherin

Tanaka

Kita

Nishizawa

et al. 2019

Sci Rep

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Skeletal muscle has remarkable regenerative potential and its decline with aging is suggested to be one of the important causes of loss of muscle mass and quality of life in elderly adults. Metabolic abnormalities such as obesity were linked with decline of muscle regeneration. On the other hand, plasma levels of adiponectin are decreased in such metabolic conditions. However, plasma levels of adiponectin have been shown to inversely correlate with muscle mass and strength in elderly people especially with chronic heart failure (CHF). Here we have addressed whether adiponectin has some impact on muscle regeneration after cardiotoxin-induced muscle injury in mice. Muscle regeneration was delayed by angiotensin II infusion, mimicking aging and CHF as reported. Adiponectin overexpression in vivo decreased necrotic region and increased regenerating myofibers. Such enhanced regeneration by excess adiponectin was also observed in adiponectin null mice, but not in T-cadherin null mice. Mechanistically, adiponectin accumulated on plasma membrane of myofibers both in mice and human, and intracellularly colocalized with endosomes positive for a multivesicular bodies/exosomes marker CD63 in regenerating myofibers. Purified high-molecular multimeric adiponectin similarly accumulated intracellularly and colocalized with CD63-positive endosomes and enhanced exosome secretion in differentiating C2C12 myotubes but not in undifferentiated myoblasts. Knockdown of T-cadherin in differentiating C2C12 myotubes attenuated both adiponectin-accumulation and adiponectin-mediated exosome production. Collectively, our studies have firstly demonstrated that adiponectin stimulates muscle regeneration through T-cadherin, where intracellular accumulation and exosome-mediated process of adiponectin may have some roles.

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Section: Discussionsupporting

confidence: 62%

“…Recent clinical studies have shown that plasma APN levels inversely correlated with muscle weakness in elderly people 31,32 , muscle mass and strength especially in heart failure patients 33 . T-cad is expressed abundantly in skeletal muscle in addition to above mentioned vascular endothelium and heart 21 .…”

Section: Introductionmentioning

confidence: 99%

Adiponectin promotes muscle regeneration through binding to T-cadherin

Tanaka

Kita

Nishizawa

et al. 2019

Sci Rep

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“…This topic has been vigorously addressed in our longitudinal cohort study for old people, known as the SONIC (i.e., septuagenarians, octogenarians, and non-agenarians investigation with centenarians) study, which investigated the age differences and similarities in factors influencing healthy aging and psychological well-being, including psychological (i.e., cognition, change in emotion and compensation, personality, and psychological development); social (i.e., socio-economic status and social relationship); and medical, dental, and nutritional aspects (61). In 353 community-dwelling older adults of approximately 83 years, Nagasawa et al deduced an association between circulating adiponectin and frailty status according to the cardiovascular health study criteria (62). The investigators found significantly higher adiponectin levels in frail subjects than in their non-frail counterparts.…”

Section: Adiponectin and Frailty In The Very Old: Another Paradoxmentioning

confidence: 99%

Adipokines and Aging: Findings From Centenarians and the Very Old

2019

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Adipose tissue, which was once considered as a simple energy storage depot, is now recognized as an active endocrine organ that regulates the whole-body energy homeostasis by secreting hundreds of bioactive substances termed adipokines. Dysregulation of adipokines is a key feature of insulin resistance and a metabolic syndrome associated with obesity. Adipokine dysregulation and insulin resistance are also associated with energy-deprivation conditions, such as frailty in old age. Previous studies have demonstrated that preserved insulin sensitivity and low prevalence of diabetes are the metabolic peculiarities of centenarians, suggesting the possible role of adipokine homeostasis in healthy longevity. Among the numerous adipokines, adiponectin is regarded as unique and salutary, showing negative correlations with several age- and obesity-related metabolic disturbances and a positive correlation with longevity and insulin sensitivity among centenarians. However, large-scale epidemiological studies have implied the opposite aspect of this adipokine as a prognostic factor for all-cause and cardiovascular mortality in patients with heart failure or kidney disease. In this review, the clinical significance of adiponectin was comparatively addressed in centenarians and the very old, in terms of frailty, cardiovascular risk, and mortality.

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“…Adipokines secreted by adipose tissues such as adiponectin were found to be associated with frailty. 5 Other adipokines such as vaspin and leptin were found to be associated with chronic diseases, but their association with frailty was not yet studied. Finding the biological correlates would allow physicians to identify frailty, monitor the progression and efficacy of interventions, and delay the onset of frailty and occurrence of disability.…”

Section: Introductionmentioning

confidence: 99%

Elevated serum Il-6 and adiponectin levels are associated with frailty and physical function in Chinese older adults

Ma¹,

Sha²,

Zhang³

et al. 2018

CIA

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PurposeFrailty is associated with adverse health outcomes. Its biological markers are essential to enhance diagnostic ease and would contribute to surveillance of the condition. Considering the involvement of pro-inflammatory and nutritional states in frailty, we aimed to investigate whether inflammatory mediators and adipokines are associated with frailty and their relationship with physical function.Patients and methodsWe recruited 130 older adults (90 nonfrail participants and 40 frail participants, mean age: 72.80±8.61 years) who underwent a comprehensive medical history and frailty assessment. The biochemical indicators (eg, blood urea nitrogen [BUN], high-density lipoprotein [HDL], and hemoglobin [HGB]), insulin pathway (glucose, insulin, and insulin-like growth factor 1 [IGF-1]), circulating inflammatory biomarkers (IL-6, tumor necrosis factor receptor 1, and C-reactive protein), and adipokines (adiponectin, vaspin, and leptin) were compared between the two groups. We further analyzed their correlation with physical function.ResultsFrail older adults showed higher levels of BUN, IL-6, adiponectin, vaspin, and glucose and lower levels of IGF-1, HDL, and HGB compared with nonfrail participants. Serum IL-6 levels were negatively correlated with both grip strength (P=0.03) and gait speed (P=0.04). Levels of circulating adiponectin and leptin were adversely correlated with grip strength (P=0.01) and gait speed (P=0.03), respectively. After adjustment for age and sex, the only markers correlated with physical function were IL-6 (r=−0.180, P=0.044) and adiponectin (r=−0.195, P=0.029).ConclusionHigh levels of IL-6, adiponectin, vaspin, and glucose as well as low levels of IGF-1 were found in frail older adults. Furthermore, IL-6, adiponectin, and leptin levels were negatively correlated with physical function, suggesting that inflammatory mediators and adipokines are biomarkers for frailty and decreased function in older adults.

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High plasma adiponectin levels are associated with frailty in a general old‐old population: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study

Cited by 27 publications

References 31 publications

Adiponectin promotes muscle regeneration through binding to T-cadherin

Adiponectin promotes muscle regeneration through binding to T-cadherin

Adipokines and Aging: Findings From Centenarians and the Very Old

Elevated serum Il-6 and adiponectin levels are associated with frailty and physical function in Chinese older adults

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