Ageing–apoptosis relation in murine spleen

• Published in: Mechanisms of ageing and development 2003-12, Vol.124 (10), p.999-1012
• Main Authors: Itzhaki, Orit, Skutelsky, Ehud, Kaptzan, Tatiana, Sinai, Judith, Michowitz, Moshe, Huszar, Monica, Leibovici, Judith
• Format: Article
• Language: English
• Subjects: Ageing; Ageing, cell death; Aging - physiology; Animals; Apoptosis; Apoptosis - physiology; Biological and medical sciences; Caspases - metabolism; Cell Division; Cell Membrane - metabolism; Cell physiology; Cell proliferation; DNA - metabolism; DNA Fragmentation; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Galactose - metabolism; Gene Expression; Liver - anatomy & histology; Macrophages - physiology; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Murine spleen; N-Acetylneuraminic Acid - metabolism; Organ Size; Spleen - anatomy & histology; Spleen - cytology; Spleen - metabolism; Spleen - physiology
• ISSN: 0047-6374; 1872-6216
• DOI: 10.1016/S0047-6374(03)00171-4

Relatively few studies have been published with regard to modification of apoptosis in normal tissues as a function of ageing. The majority of these studies demonstrated an increase in programmed cell death (PCD) with age. However, opposite results, namely loss of apoptotic control with age, have also been reported. In the present study, we examined proliferation and apoptotic cell death in spleens of C57/BL mice of different ages. A tendency towards decrease in cell proliferative capacity was seen with age. By contrast, apoptosis was increased in spleens from aged animals. Moreover, the proliferative cell/apoptotic cell ratio decreased in function of age. Ladder type DNA degradation was much more pronounced in DNA derived from splenocytes of old mice. These results were supported by a decrease of Bcl-2 and an increase in Fas receptor expression as well as by increased activation of caspases 8, 3 and 9 in splenocytes from aged animals. In addition, cell surface molecular markers recognizable by macrophages in apoptotic cells, namely decreased sialic acid concomitant with increased unmasking of galactose residues, were more pronounced on splenocytes from old mice than on those from young animals. In addition to the experimental evidence which supports a role of apoptotic cell death in ageing, a series of theoretical reasoning, which could also favor this possibility, are discussed.