Hang Zhang, Junwei Huang, Peiyu Lin, Jiayin Song, Chonghui Hu, Biaojun Lin, Lingdan Le, Shangyou Zheng
Aging biomarkers, particularly in accelerated aging populations, are significantly associated with pancreatic disease risk, with potential implications for clinical risk stratification. Circulating lipid biomarkers were identified as potential statistical mediators of the association between PhenoAgeAccel and pancreatic diseases.
BACKGROUND: Biological aging refers to gradual declines in overall physiological function and can raise susceptibility to diseases. However, whether biological age acceleration is associated with pancreatic diseases remains unclear.
METHODS: In UK Biobank, 326,873 adults recruited in 2006-2010 were included. Klemera-Doubal Method Biological Age Acceleration (KDMAgeAccel) and Phenotypic Age Acceleration (PhenoAgeAccel) were categorized (G1-G4 by standard deviation [SD]) and modeled continuously. We examined the associations and dose-response relationships between acceleration and the following clinical outcomes: overall pancreatic diseases, acute pancreatitis, chronic pancreatitis, pancreatic cysts, pancreatic cancer, and pancreas-related mortality. Cohen's d, independent t-tests, multivariable Cox proportional hazards regression, and causal mediation analysis were used to assess differences between aging groups, disease associations, and the mediation effects of circulating lipid biomarkers.
RESULTS: KDMAgeAccel and PhenoAgeAccel demonstrated significant associations with pancreatic disease risk (both P < 0.05). PhenoAgeAccel demonstrated significant non-linear associations with overall pancreatic diseases, pancreatic cysts, pancreatic cancer, and pancreas-related mortality (all P for non-linearity <0.05), while no significant non-linearity was observed for acute pancreatitis or chronic pancreatitis (both P for non-linearity >0.05). In the fully adjusted Cox model, compared with G1, the PhenoAgeAccel G4 group had higher risks of all pancreatic diseases (hazard ratio [HR] 1.706, 95% confidence interval [CI] 1.513-1.923), acute pancreatitis (1.637, 1.352-1.981), chronic pancreatitis (3.551, 2.248-5.609), pancreatic cysts (1.547, 1.128-2.122), pancreatic cancer (1.387, 1.123-1.713), and pancreas-related mortality (1.442, 1.139-1.824).Circulating lipid biomarkers partially mediated the association between PhenoAgeAccel and pancreatic diseases, with notable contributions from free cholesterol in small LDL (6.66% for chronic pancreatitis), cholesterol to total lipids ratio in medium LDL (8.54% for acute pancreatitis), and cholesterol to total lipids ratio in large LDL (8.06% for pancreatic cancer).
CONCLUSIONS: Aging biomarkers, particularly in accelerated aging populations, are significantly associated with pancreatic disease risk, with potential implications for clinical risk stratification. Circulating lipid biomarkers were identified as potential statistical mediators of the association between PhenoAgeAccel and pancreatic diseases.