Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.

BACKGROUND: With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. METHODS: Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. RESULTS: The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: ß = 0.741; NHANES: ß = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel. CONCLUSIONS: Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

Weight change across adulthood and accelerated biological aging in middle-aged and older adults.

BACKGROUND: Little is known regarding the association between weight change and accelerated aging. OBJECTIVES: This study aimed to estimate the influence of weight change across adulthood on biological aging acceleration in middle-aged and older adults in the United States. METHODS: We used data of 5553 adults (40-84 y) from the National Health and Nutrition Examination Survey 1999-2010. Weight change patterns (i.e., stable normal, maximal overweight, obese to nonobese, nonobese to obese, and stable obese) and absolute weight change groups across adulthood (i.e., from young to middle adulthood, young to late adulthood, and middle to late adulthood) were defined. A biological aging measure (i.e., phenotypic age acceleration [PhenoAgeAccel]) at late adulthood was calculated. Survey analysis procedures with the survey weights were performed. RESULTS: Across adulthood, maximal overweight, nonobese to obese, and stable obesity were consistently associated with higher PhenoAgeAccel. For instance, from young to middle adulthood, compared with participants who had stable normal weight, participants experiencing maximal overweight, moving from the nonobese to obese, and maintaining obesity had 1.71 (standard error [SE], 0.21; P < 0.001), 3.62 (SE, 0.28; P < 0.001), and 6.61 (SE, 0.58; P < 0.001) higher PhenoAgeAccel values, respectively. From young to middle adulthood, relative to absolute weight loss or gain of <2.5 kg, weight loss of ≥2.5 kg was marginally associated with lower PhenoAgeAccel (P = 0.054), whereas an obese to nonobese pattern from middle to late adulthood was associated with higher PhenoAgeAccel (P < 0.001). CONCLUSIONS: Maximal overweight, nonobese to obese, and stable obesity across adulthood, as well as an obese to nonobese pattern from middle to late adulthood, were associated with accelerated biological aging. In contrast, weight loss from young to middle adulthood was associated with decelerated biological aging. The findings highlight the potential role of weight management across adulthood for aging. Monitoring weight fluctuation may help identify the population at high risk of accelerated aging.

Relationship among Serum Homocysteine, Intercellular Adhesion Molecule-1, Monocyte Chemoattractant Protein-1, and Visual Impairment in Diabetic Macular Edema.

OBJECTIVE: To determine the relationship among serum homocysteine (Hcy), intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1 (MCP-1) and visual impairment in patients with diabetic macular edema (DME). STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Yulin Second Hospital, China, from April 2018 to May 2021. METHODOLOGY: A total of 132 patients with diabetic retinopathy (DR), complicated with DME, were selected as observation group; and 132 patients with simple DR were included in the control group. According to visual examination, patients in observation group were divided into visual disability and non-visual disability. Serum Hcy, ICAM-1, MCP-1, and other indicators were measured. RESULTS: Duration of diabetes, levels of serum Hcy, ICAM-1 and MCP-1 in observation group were higher than those in control group (all p <0.001). Levels of serum Hcy, ICAM-1 and MCP-1 in patients with mild, moderate and severe DME were significantly different (all p <0.001). Levels of serum Hcy, ICAM-1 and MCP-1 in patients with visual disabilities were higher than those in patients with non-visual disabilities (all p <0.001). Levels of serum Hcy, ICAM-1 and MCP-1 in visually disabled patients were higher than those in non-visual disability patients (all p <0.001). CONCLUSION: Levels of serum Hcy, ICAM-1 and MCP-1 in patients with DR complicated with DME were higher than those without visual disability; and levels of Hcy, ICAM-1 and MCP-1 in patients with visual disability were higher than those without visual disability. In patients with DR complicated with DME, increase of these serum markers may play an important role in visual disability. Key Words: Diabetic retinopathy (DR), Diabetic macular edema (DME), Hcy, ICAM-1, MCP-1, Visual impairment.

Clinical study of 99mTc-3P-RGD2 peptide imaging in osteolytic bone metastasis.

OBJECTIVE: To investigate the value of integrin αvß3 targeted imaging with 99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2 (99mTc-3P-RGD2) as a radiotracer in dectecting osteolytic bone metastases. METHODS: This is a retrospective study involving a cohort of 69 consecutive patients including 59 with lung cancer and 10 with other cancers. Patients were required to receive whole body scan (WBS) and regional SPECT/CT imaging with 99mTc-3P-RGD2 (RGD imaging) and 99mTc-MDP (MDP imaging) as a radiotracer successively within days. Final diagnosis was based on comprehensive assessment of all available data including case history, CT, MRI, SPECT/CT, PET/CT, histopathology and 6-12 months follow-up. Visual observation and semiquantitative analysis (T/N: tracer uptake ratio of osteolytic metastases to normal bone) of 99mTc-3P-RGD2 or 99mTc-MDP imaging were performed and their detective values for osteolytic metastases were compared. RESULTS: A total of 131 osteolytic metastatic lesions were retrospectively studied. Osteolytic metastases mainly presented as "hot region", occasionally as "cool or normal region" on RGD imaging. The detection sensitivity of RGD WBS for osteolytic metastases was significantly higher than that of 99mTc-MDP WBS (80.9% vs. 46.6%, p<0.01). The sensitivity increased to 96.2% (126/131) when combining with SPECT/CT. 99mTc-3P-RGD2 imaging also promoted the detection of unknown primary tumor, lymph node metastases and offered information for clinical staging. T/N of 99mTc-3P-RGD2 in lung adenocarcinoma osteolytic metastases showed no statistical difference compared with that in squamous-cell carcinoma (6.84±3.46 vs. 7.33±3.22, t = 0.39, p = 0.71). Whereas, it was higher in osteolytic metastases from lung cancer than that from thyroid cancer (7.05±3.01 vs. 4.11±2.67, p = 0.03). CONCLUSION: 99mTc-3P-RGD2 peptide imaging showed great potential for detection of osteolytic bone metastasis due to high expression level of integrin αvß3 on osteoclast and most tumor cells.