Understanding the Unique Microenvironment in the Aging Liver

Abstract

In the past decades, many studies have focused on aging because of our pursuit of longevity. With lifespans extended, the regenerative capacity of the liver gradually declines due to the existence of aging. This is partially due to the unique microenvironment in the aged liver, which affects a series of physiological processes. In this review, we summarize the related researches in the last decade and try to highlight the aging-related alterations in the aged liver.

Chemical composition and anti-aging effects of standardized herbal chicken essence on D-galactose- induced senescent mice

“…Owing to the complexity of the aging process and no universally acceptable single-measurement biomarker of aging is presently known ( 45 ), the evidence from several findings, in both animal and human liver specimens, has indicated the presence of specific aging hallmarks in the diseases involving the hepatic compartments; thus, the liver is regarded as an important organ for use in evaluating the aging biomarkers ( 45 – 47 ). D-Gal-induced aging in mice can cause hepatic cell swelling, necrosis, inflammatory cell infiltration, and other pathological changes, leading to liver damage ( 48 ).…”

Angiocrine Signaling in Sinusoidal Health and Disease

“…LSEC regulation of HSC activation and quiescence via VEGF-stimulated NO production is critical for sinusoidal homeostasis, 73 but aging results in increased activation and transdifferentiation of HSCs into myofibroblasts, as well as HSC hyperplasia, lipid drop alterations, telomere attrition, impaired release of Asig proteins such as HGF, and finally impaired production of ECM components such as laminin. 108 114 115 This failure of LSEC to maintain HSC quiescence with age was also associated with significantly increased macrophage infiltration in rodent models and altered gene expression of sinusoidal protective pathways in young and aged cirrhosis patients. 109…”

“…Aging impacts endothelial dysfunction and liver disease. 40,59,[105][106][107][108] Aging amplifies pathogenic injury mechanisms, increases inflammation, and impairs sinusoidal function. Age-related LSEC pseudocapillarization results in fenestrae loss, increased basement membrane thickness, similar but less severe than fibrosis, 105,109 and microvascular rarefication (MVR) 110 which impedes the transport between the sinusoidal circulation and space of Disse.…”

Emerging Roles of Spatial Transcriptomics in Liver Research

“…Aging is strongly associated with reduced hepatic function. 82 Nikoopoulou et al adapted 10x Visium technology as well as single-cell RNA-seq and ATAC-seq to livers from young (3-4 months) and old (18-22 months) mice and revealed…”