The Klotho gene is recognized for its anti-aging properties. Its downregulation leads to aging-like phenotypes, whereas overexpression can extend lifespan. Klotho protein exists in three forms: α-klotho, β-klotho and γ-klotho. The α-klotho has two isoforms: a membrane-bound form, primarily in the kidney and brain, and a secreted klotho protein present in blood, urine, and cerebrospinal fluid. Klotho functions as a co-receptor for fibroblast growth factor-23 (FGF23), regulating phosphate metabolism. The membrane-bound form controls various ion channels and receptors, while the secreted form regulates endocrine FGFs, including FGF19 and FGF21. The interaction between β-klotho and FGF21 in muscle is critical in the development of sarcopenic obesity. This systematic review, registered in PROSPERO and conducted following PRISMA guidelines, evaluates klotho levels in individuals with obesity or sarcopenic obesity. The study includes overweight, obese, and sarcopenic obese adults compared to those with a normal body mass index. After reviewing 713 articles, 20 studies were selected, including observational, cross-sectional, cohort studies, and clinical trials. Significant associations between klotho levels and obesity, metabolic syndrome (MS), and cardiovascular risk were observed. Exercise and dietary interventions positively influenced klotho levels, which were linked to improved muscle strength and slower decline. Klotho is a potential biomarker for obesity, MS, and sarcopenic obesity. Further research is needed to explore its mechanisms and therapeutic potential.

Background/Objectives: Long-term comparative data on body composition (BC) trajectories following different bariatric procedures remain limited, particularly regarding potential muscle preservation after malabsorptive techniques. We aimed to compare 5-year changes in adiposity and muscle mass following biliopancreatic diversion (BPD), Roux-en-Y gastric bypass (RYGB), and sleeve gastrectomy (SG), adjusting for baseline heterogeneity. Methods: In this retrospective longitudinal study, 128 patients with severe obesity were followed for 60 months. BC was assessed annually using multi-frequency bioelectrical impedance analysis. Multivariable linear mixed-effects models adjusted for baseline BMI, age, and sex were used to evaluate trajectories of total weight loss (%WL), fat mass loss (%FML), and skeletal muscle mass (SMM). Results: BPD demonstrated a significantly superior longitudinal trajectory for %WL (β = 0.124 [95% CI: 0.013–0.235], p = 0.028) and %FML (β = 0.288 [95% CI: 0.135–0.440], p < 0.001) over 5 years. However, no statistically significant independent differences between techniques were observed at the isolated 60-month endpoint after full adjustment. Although BPD was associated with a higher percentage of muscle mass loss (p = 0.019), absolute skeletal and appendicular muscle mass did not differ significantly across procedures. Age emerged as an independent negative predictor of weight and fat loss (p < 0.001). Conclusions: After rigorous adjustment for baseline characteristics, BPD provides greater long-term adiposity reduction without evidence of disproportionate impairment of absolute muscle mass compared with RYGB or SG. These findings contribute to a more refined understanding of long-term body composition dynamics following bariatric surgery.

This pilot study aimed to investigate the role of the Klotho/FGF (fibroblast growth factor) system in biological features associated with premature aging, particularly inflammation and muscle dysfunction, focusing on its association with inflammatory markers, body composition, and muscle function in middle-aged adults. A total of 45 participants aged 50–60 years were enrolled, including 30 patients with obesity (22F/8M) and 15 healthy controls (11F/4M). Comprehensive assessments were conducted, including body composition analysis and muscle function tests. Evaluations of protein expression of Klotho, β-Klotho, FGF19, FGF21, FGF23, TFN-α and IL-10 were assessed in peripheral blood mononuclear cells (PBMCs). A Principal Component Analysis (PCA) was carried out to explore the relationships among variables. Significant differences were observed between the obese and control groups, with obese individuals exhibiting lower levels of Klotho and higher levels of TFN-α. The PCA revealed that higher Klotho levels were positively associated with better muscle function and lower inflammatory markers. These associations suggest that Klotho-related alterations may reflect biological processes linked to inflammation and muscle dysfunction in obesity. These findings suggest that alterations in the Klotho/FGF system may reflect biological pathways commonly associated with aging-related phenotypes in obesity, rather than direct measures of chronological aging. Given the exploratory design and limited sample size, these findings should be interpreted as hypothesis-generating rather than evidence of causal mechanisms.