Aging-Related Changes in the Ultrastructure of Hepatocytes and Cardiomyocytes of Elderly Mice Are Enhanced in ApoE-Deficient Animals

Abstract

Biological aging is associated with various morphological and functional changes, yet the mechanisms of these phenomena remain unclear in many tissues and organs. Hyperlipidemia is among the factors putatively involved in the aging of the liver and heart. Here, we analyzed morphological, ultrastructural, and biochemical features in adult (7-month-old) and elderly (17-month-old) mice, and then compared age-related features between wild type (C57Bl/6 strain) and ApoE-deficient (transgenic ApoE−/−) animals. Increased numbers of damaged mitochondria, lysosomes, and lipid depositions were observed in the hepatocytes of elderly animals. Importantly, these aging-related changes were significantly stronger in hepatocytes from ApoE-deficient animals. An increased number of damaged mitochondria was observed in the cardiomyocytes of elderly animals. However, the difference between wild type and ApoE-deficient mice was expressed in the larger size of mitochondria detected in the transgenic animals. Moreover, a few aging-related differences were noted between wild type and ApoE-deficient mice at the level of plasma biochemical markers. Levels of cholesterol and HDL increased in the plasma of elderly ApoE−/− mice and were markedly higher than in the plasma of elderly wild type animals. On the other hand, the activity of alanine transaminase (ALT) decreased in the plasma of elderly ApoE−/− mice and was markedly lower than in the plasma of elderly wild type animals.

Short-term fenofibrate treatment improves ultrastructure of hepatocytes of old rats

“…Similar increase in lipid droplets were found in the liver of aging mice [21,31]. Interestingly, in Fischer 344 male rats the volume of lipid droplets in hepatocytes undergoes a biphasic response during aging, i.e.…”

“…Łysek-Gładysińska et al observed increased number of damaged mitochondria in the hepatocytes of 17-month-old mice as compared to 6-month old animals [21]. Interestingly, no age-dependent increase in hydrogen peroxide release relative to the amount of oxygen consumed was observed in the isolated murine liver mitochondria [18].…”

“…It has been showed that aging in rodents is associated with some decline of mitochondrial function with mitochondria from old mice characterized by less regular and more heterogeneous cristae not arranged in parallel stacks [18], and increased content of oxidation products of phospholipids, proteins and DNA, decreased membrane potential, and increased mitochondrial size and fragility [19]. It was revealed that aging in rodents [20][21][22] and humans [22] is associated with the increase in individual mitochondrial volume and decline in the number of mitochondria in the liver. These findings are supported by our observation of the increased matrix electron density of mitochondria in hepatocytes of old rats.…”

Mesenchymal stem cells reverse thymus aging by reprogramming the DNA methylation of thymic epithelial cells

“…Therefore, we used human TECs as the research object, induced aging by H 2 O 2 , and observed the effect of intervention with MSCs. H 2 O 2 is a small molecule that induce cell senescence due to oxidative stress caused by high levels of free radicals produced by the cell membrane, and increase the activity of SA-β-gal and expression of P16 and P21 [ [26] , [27] , [28] ], which were consisted with our results that the changes of TECs after treatment with 200 μmol/L H 2 O 2 for 72 h. Interestingly, when senescent TECs were cocultured with MSCs in Transwell chambers for 48 h, the activity of SA-β-gal decreased, and P16 and P21 down-regulated, chromatin was evenly distributed, and autophagosomes were observed. Moreover, under a Nanolive 4D microscope, it was found that MSCs continuously secreted vesicular substances into ageing TECs, resulting in uniform distribution of TEC chromatin, appearance of intracellular autophagosomes and smaller cell morphology.…”

Vitamin K2 (MK-7) Intercepts Keap-1/Nrf-2/HO-1 Pathway and Hinders Inflammatory/Apoptotic Signaling and Liver Aging in Naturally Aging Rat

“…The aging process is associated with a gradual dysregulation of genomic, cellular, tissue and whole-organism homeostasis, leading to a compromised ability to respond to stress, deteriorated function and increased morbidity and mortality risks. Moreover, these changes lead to serious pathologies, including cardiovascular disorders, diabetes, neurodegenerative diseases and cancer [ 3 ].…”