Aging accelerates but life-long dietary restriction suppresses apoptosis-related Fas expression on hepatocytes

• Published in: The American journal of pathology Vol. 151; no. 3; pp. 659 - 663
• Main Authors: Higami, Y, Shimokawa, I, Tomita, M, Okimoto, T, Koji, T, Kobayashi, N, Ikeda, T
• Format: Journal Article
• Language: English
• Published: Bethesda, MD ASIP 01.09.1997; American Society for Investigative Pathology
• Subjects: Aging; Animals; Apoptosis; Biological and medical sciences; Energy Intake; fas Receptor - genetics; Gastroenterology. Liver. Pancreas. Abdomen; Immunohistochemistry; Liver - metabolism; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Other diseases. Semiology; Polymerase Chain Reaction; Rats; Rats, Inbred F344; RNA, Messenger - metabolism; Immunohistochemistry; Senescence; Rat; Liver; Rodentia; Hepatic disease; Polymerase chain reaction; Pathology; Vertebrata; Experimental disease; Mammalia; Hepatocyte; Animal; Digestive diseases; Molecular biology; Restricted diet; Apoptosis
• ISSN: 0002-9440; 1525-2191

Aging enhances apoptosis of hepatocytes under normal physiological conditions and increases the susceptibility of hepatocytes to apoptosis whereas life-long dietary restriction suppresses the age-enhanced susceptibility to apoptosis. We examined the subcellular mechanisms of the age-associated changes and effect of dietary restriction using quantitative reverse transcription polymerase chain reaction and immunohistochemistry for Fas in the livers of 6- and 24-month-old male Fischer 344 rats fed ad libitum or 70% diet restricted. We also analyzed the level of ordinary and variant forms of Fas mRNA. The ordinary form of Fas mRNA, but not the variant form of Fas mRNA, significantly increased with age. Dietary restriction significantly suppressed the ordinary form of Fas mRNA in advanced age. Aging enhanced Fas immunoreactivity in the hyperplastic bile epithelium and hepatocytes whereas dietary restriction suppressed it. Our findings indicate that Fas protein, particularly the ordinary form of Fas, is involved in age-associated apoptosis of hepatocytes. Fas overexpression in advanced age may explain the age-enhanced susceptibility to apoptosis. Our results also suggest that dietary restriction suppresses Fas overexpression, resulting in a reduction of the age-enhanced susceptibility to apoptosis.