From the experiments of progeria-like syndrome, Selye proposed that calciphylaxis was an important factor in tissue aging processes. The purpose of this study was to try to reestimate his hypothesis, to clarify that the changes of connective tissue metabolism might precede the calciphylaxis, and to clarify the relationships between serum glycoprotein components and connective tissue metabolism. Female Wistar rats were divided in five groups, of which control group I were killed for analysis before experiment. Another four groups were control group II (no treatment), D-2 group (calciferol oral administration, daily), DHT group (dihydrotachysterol oral administration, daily), and D-2+DS group (D-2+dextran sulfate=MDS-Kowa intravenous administration, daily). Four weeks after feeding, D-2 group showed progeria-like syndrome, whereas DHT group showed minimal change probably for its insufficient DHT doses. D-2+DS group resembled D-2 group but their appearences were not so marked than D-2 group. Uronic acid (UA), hexosamine (HA), hydroxyproline (×100/13.2=collagen) were analysed with each aorta, rib cartilage and skin. Histological examinations were done with aorta and skin. The results were as follows: Comparing control II with control I: decreasing tendency of HA in aorta, increasing tendency of HA in rib cartilage, and increase of collagen in all tissues were observed. Comparing D-2 group with control II: non-significant changes of HA, UA in aorta, and significant decrease of both HA and UA in rib cartilage and skin were observed. Collagen was increased in all tissues. Comparing DHT group with control II: non-significant changes of HA, UA and increase of collagen were observed. Comparing D-2+DS group with D-2 group: higher HA, UA and lower collagen contents than D-2 group were observed. Histological observations: in D-2 group, arteriosclerotic changes were observed from media to intima of aorta, namely, rupture and fragmentation of elastic fibers, increased PAS positive substances and deposition of calcium. In D-2+DS group, aorta showed changes those like D-2 group with lesser degree of PAS positive substances and calcium deposition than D-2 group. In DHT group, arteriosclerotic changes were not revealed. The serum hexosamine levels were high in D-2 group, low in control I, and those of control II were intermediate. There were no lineal correlations between serum hexosamine levels and tissue hexosamine contents. These results indicate, 1) changes of connective tissue components in progeria-like syndrome are similar to those in physiological aging, 2) lesser calcium deposition relates lesser aged appearences, 3) preceding the calcium deposition, changes of connective tissue metabolism going on, and 4) serum hexosamine changes seem, in part, to refer to changes of connective tissue metabolism.
The accumulation of age pigment or lipofuscin is one of the most consistnet morphological changes in the nerve cells of aged animals. Howeve, little information is available regarding the age-related biochemical changes in the nervous system. For the purpose of obtaining some age-related biochemical changes, the effect of age and environmental factors on the lipoperoxidizability of the brain were studied in rats and following results were obtained. 1) Lipid peroxidizability of the brain increases with advancing age showing a positive correlation. 2) This increase of lipid-peroxide may be inhibited by administration of antioxidants, such as α-tocopherol and α-tocopheryl felurate. 3) In VE-deficient rat, lipid peroxidizability of the brain appeared to be accerelated. However, the difference of lipid-peroxide content in the brain between control and VE-deficientcy groups tended to decrease with advancing age. 4) Administration of peroxide of linoleic acid or acetanilid also caused the increase of lipoperoxide in the brain. These results are interesting in suggesting a biochemical process for the formation of lipofuscin as well as presenting an evidence to support “Free Radical Theory of Aging”.
In connection with the significant role of serum phospholipids in arteriosclerosis, the concentration of various phospholipids and cholesterol was estimated in sera of normal adult as well as of patients with arteriosclerosis. Methods: Lipids were extracted from serum by the method of Floch and six phospholipids fractions (lysolecithin, sphingomyelin, lecithin, phosphatidyl-serine plus phosphatidyl-inositol, phosphatidyl-inositol, phosphatidyl-ethanolamine and phosphatidic acid) were separated by use of the thin layer chromatography of Skipski's Method modified by Tashiro. The fractionation was quantitatively performed, since the recovery of the individual lipids estimated from phosphorus was 92 to 96 per cent. Results: (1) In normal adults, the content of the total phospholipids in serum was 160mg/dl, and the composition of individual phospholipids was also relatively constant at the age of 20 years as well as 50 years. Furthermore, the individual values of phospholipids were not significantly altered in sera collected every 10 days. (2) In serum of patients with arteriosclerosis, on the other hand, the concentration either of total phospholipids, lecithin, ph-ethanolamine, ph-inositol plus ph-serine, or total cholesterol, as well as the C/P ratio were significantly higher than those of normal serum. In view of the increased content of ph-inositol, -serine and -ethanolamine in serum, the blood coagulability must be considered as rather high in the arteriosclerotic. (3) When dextran sulfate was administered in patients with arteriosclerosis, the content of total phospholipids, lecithin and cholesterol was decreased, while the values of cholesterol, ph-inositol+ph-serine and C/P ratio were decreased by the administration of ethylnandrol.