A biomarker framework for liver aging: the Aging Biomarker Consortium consensus statement

Abstract

In human aging, liver aging per se not only increases susceptibility to liver diseases but also increases vulnerability of other organs given its central role in regulating metabolism. Total liver function tends to be well maintained in the healthy elderly, so liver aging is generally difficult to identify early. In response to this critical challenge, the Aging Biomarker Consortium of China has formulated an expert consensus on biomarkers of liver aging by synthesizing the latest scientific literature, comprising insights from both scientists and clinicians. This consensus provides a comprehensive assessment of biomarkers associated with liver aging and presents a systematic framework to characterize these into three dimensions: functional, imaging, and humoral. For the functional domain, we highlight biomarkers associated with cholesterol metabolism and liver-related coagulation function. For the imaging domain, we note that hepatic steatosis and liver blood flow can serve as measurable biomarkers for liver aging. Finally, in the humoral domain, we pinpoint hepatokines and enzymatic alterations worthy of attention. The aim of this expert consensus is to establish a foundation for assessing the extent of liver aging and identify early signs of liver aging-related diseases, thereby improving liver health and the healthy life expectancy of the elderly population.

Figure 1.

Framework of biomarkers for liver aging. The proposed framework for liver aging consists of three dimensions: functional, imaging, and humoral biomarkers. Abbreviations: ALP, alkaline phosphatase; ALT, aminotransferase; APOC4, apolipoprotein C4; APOE, apolipoprotein E; C4, 7α-hydroxy-4-cholesten-3-one; CHI3L1, chitotriosidase-3-like protein 1; CRP, C-reaction protein; CT, computed tomography; DNAm: DNA methylation; GGT, gamma-glutamyl transferase; HC II, heparin cofactor II; HDL-C, high-density lipoprotein cholesterol; IGF-1, insulin-like growth factor 1; LDL-C, low-density lipoprotein cholesterol; LM, lipid metabolism; MANF, mesencephalic astrocyte-derived neurotrophic factor; MRI, magnetic resonance imaging; OPN, osteopontin; PCSK9, proprotein convertase subtilisin/kexin type 9; PDFF, proton density fat fraction; PW Doppler, pulsed-wave Doppler; TC, total cholesterol; TG, triglycerides.