BACKGROUND: Biological aging is a physiological process that can be altered by various factors. The presence of a chronic metabolic disease can accelerate aging and increase the risk of further chronic diseases. The aim of the study was to determine whether the presence of metabolic syndrome (MetS) affects levels of markers that are associated with, among other things, aging. MATERIAL AND METHODS: A total of 169 subjects (58 with MetS, and 111 without metabolic syndrome, i.e., non-MetS) participated in the study. Levels of telomerase, GDF11/15, sirtuin 1, follistatin, NLRP3, AGEs, klotho, DNA/RNA damage, NAD+, vitamin D, and blood lipids were assessed from blood samples using specific enzyme-linked immunosorbent assay (ELISA) kits. RESULTS: Telomerase (p < 0.01), DNA/RNA damage (p < 0.006) and GDF15 (p < 0.02) were higher in MetS group compared to non-MetS group. Only vitamin D levels were higher in the non-MetS group (p < 0.0002). Differences between MetS and non-MetS persons were also detected in groups divided according to age: in under 35-year-olds and those aged 35-50 years. CONCLUSIONS: Our results show that people with MetS compared to those without MetS have higher levels of some of the measured markers of biological aging. Thus, the presence of MetS may accelerate biological aging, which may be associated with an increased risk of chronic comorbidities that accompany MetS (cardiovascular, inflammatory, autoimmune, neurodegenerative, metabolic, or cancer diseases) and risk of premature death from all causes.

• Keywords
• AGEs, DNA/RNA damage GDF11/15, NAD+, NLRP3, aging, follistatin, klotho, metabolic syndrome, sirtuin 1, telomerase, vitamin D,
• Publication type
• Journal Article MeSH

OBJECTIVE: GDF11 is a member of the TGF-β superfamily that was recently implicated as potential "rejuvenating" factor, which can ameliorate metabolic disorders. The main objective of the presented study was to closely characterize the role of GDF11 signaling in the glucose homeostasis and in the differentiation of white adipose tissue. METHODS: We performed microscopy imaging, biochemical and transcriptomic analyses of adipose tissues of 9 weeks old ob/ob mice and murine and human pre-adipocyte cell lines. RESULTS: Our in vivo experiments employing GDF11 treatment in ob/ob mice showed improved glucose/insulin homeostasis, decreased weight gain and white adipocyte size. Furthermore, GDF11 treatment inhibited adipogenesis in pre-adipocytes by ALK5-SMAD2/3 activation in cooperation with the WNT/β-catenin pathway, whose inhibition resulted in adipogenic differentiation. Lastly, we observed significantly elevated levels of the adipokine hormone adiponectin and increased glucose uptake by mature adipocytes upon GDF11 exposure. CONCLUSION: We show evidence that link GDF11 to adipogenic differentiation, glucose, and insulin homeostasis, which are pointing towards potential beneficial effects of GDF11-based "anti-obesity" therapy.

• MeSH
• Adipogenesis * MeSH
• Adiponectin metabolism   MeSH
• beta Catenin * metabolism   MeSH
• Cell Differentiation physiology   MeSH
• Glucose metabolism   MeSH
• Insulin metabolism   MeSH
• Bone Morphogenetic Proteins metabolism   MeSH
• Humans MeSH
• Mice MeSH
• Smad2 Protein MeSH
• Smad3 Protein MeSH
• Smad Proteins, Receptor-Regulated MeSH
• Growth Differentiation Factors metabolism   MeSH
• Wnt Signaling Pathway MeSH
• Receptor, Transforming Growth Factor-beta Type I MeSH
• Transforming Growth Factor beta metabolism   MeSH
• Adipocytes metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Adiponectin MeSH
• beta Catenin * MeSH
• GDF11 protein, human MeSH Browser
• Gdf11 protein, mouse MeSH Browser
• Glucose MeSH
• Insulin MeSH
• Bone Morphogenetic Proteins MeSH
• Smad2 Protein MeSH
• Smad3 Protein MeSH
• Smad Proteins, Receptor-Regulated MeSH
• Growth Differentiation Factors MeSH
• SMAD2 protein, human MeSH Browser
• Smad2 protein, mouse MeSH Browser
• SMAD3 protein, human MeSH Browser
• Smad3 protein, mouse MeSH Browser
• Receptor, Transforming Growth Factor-beta Type I MeSH
• TGFBR1 protein, human MeSH Browser
• Tgfbr1 protein, mouse MeSH Browser
• Transforming Growth Factor beta MeSH

Studies over the past 30 years have revealed that adipose tissue is the major endocrine and paracrine organ of the human body. Arguably, adiopobiology has taken its reasonable place in studying obesity and related cardiometabolic diseases (CMDs), including Alzheimer's disease (AD), which is viewed herein as a neurometabolic disorder. The pathogenesis and therapy of these diseases are multiplex at basic, clinical and translational levels. Our present goal is to describe new developments in cardiometabolic and neurometabolic adipobiology. Accordingly, we focus on adipose- and/or skeletal muscle-derived signaling proteins (adipsin, adiponectin, nerve growth factor, brain-derived neuroptrophic factor, neurotrophin-3, irisin, sirtuins, Klotho, neprilysin, follistatin-like protein-1, meteorin-like (metrnl), as well as growth differentiation factor 11) as examples of metabotrophic factors (MTFs) implicated in the pathogenesis and therapy of obesity and related CMDs. We argue that these pathologies are MTF-deficient diseases. In 1993 the "vascular hypothesis of AD" was published and in the present review we propose the "vasculometabolic hypothesis of AD." We discuss how MTFs could bridge CMDs and neurodegenerative diseases, such as AD. Greater insights on how to manage the MTF network would provide benefits to the quality of human life.

• Keywords
• Alzheimer’s disease, BDNF, Klotho, NGF, adipokines, adiponectin, cardiometabolic diseases, irisin, metabotrophic factors,
• MeSH
• Adipokines metabolism   MeSH
• Molecular Targeted Therapy methods   MeSH
• Humans MeSH
• Metabolic Syndrome drug therapy   metabolism   MeSH
• Neurodegenerative Diseases drug therapy   metabolism   MeSH
• Neuropeptides metabolism   MeSH
• Nerve Growth Factors metabolism   MeSH
• Signal Transduction MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• Adipokines MeSH
• Neuropeptides MeSH
• Nerve Growth Factors MeSH