Morphological aspects of aging liver: half a century of progress in Japan

The most important morphological aspects of the physiological changes of the liver with age are decreases in the numbers of hepatocytes and their mitochondria, coupled with increases in their volumes. The latter is considered to partially compensate for the decrease in numbers of hepatocytes and mitochondria, but leads to a more limited reserve capacity and thus to a condition in which liver function can be more readily exhausted. The binuclearity and polyploidization of the hepatocytes increase with age and are considered to be due to inhibition of their cell division process. Our studies on the parabiosis between young and old rats and mice, on the implantation of isolated hepatocytes in the spleens of rats of different ages, and on the regenerative process after partial hepatectomy in rats of different ages, suggested the existence of humoral inhibitory factor(s) for the division of the cells and their mitochondria. Morphological studies on the native and Hawaiian Japanese, as well as on the USA Caucasians and the Costa Rican Latinos revealed that a difference in the process of the age-related decrease in hepatocyte number among different ethnicities is mainly due to differences in nutritional conditions rather than to genetic factors. Experimental studies are now being carried out on the effect(s) of various dietary conditions on age-related changes of the liver, and the results obtained support the findings of the geographical studies.