Ishigami Akihito, Kondo Yoshitaka, Nanba Reiko, Ohsawa Takako, Handa Setsuko, Kubo Sachiho, Akita Masumi, Maruyama Naoki
Organ Disorder and Aging Research Group, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo 173-0015, Japan.
Biochem Biophys Res Commun. 2004 Mar 12;315(3):575-80. doi: 10.1016/j.bbrc.2004.01.091.
Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with aging. SMP30-deficient (SMP30Y/-) mice are viable and fertile but lower in body weight and shorter in life span than the wild-type. In the electron microscope, hepatocytes from SMP30Y/- but not the wild-type mice at 12 months of age clearly contained many lipid droplets, abnormally enlarged mitochondria with indistinct cristae, and enlarged lysosomes filled with electron-dense bodies. In liver specimens from SMP30Y/- mice, the marked number of lipid droplets visible around the central vein increased notably in size and amount as the animals aged. Biochemical analysis of neutral lipids, total hepatic triglyceride, and cholesterol from SMP30Y/- mice showed approximately 3.6- and 3.3-fold higher levels, respectively, than those from age-matched wild-type mice. Moreover, values for total hepatic phospholipids from SMP30Y/- mice were approximately 3.7-fold higher than those for their wild-type counterparts. By thin-layer chromatography analysis, phosphatidylethanolamine, cardiolipin, phosphatidylcholine, phosphatidylserine, and sphingomyelin accumulations were detected separately in lipid extracts from SMP30Y/- mouse livers and provided results that strongly indicate the profound effect of an SMP30 deficiency on the metabolism of these neutral lipids and phospholipids. Conceivably, this abnormality of lipid metabolism is sufficient to curtail the life span of SMP30-deficient mice.
衰老标记蛋白-30（SMP30）是一种与雄激素无关的因子，其水平会随着衰老而降低。SMP30基因缺陷（SMP30Y/-）小鼠能够存活且可育，但与野生型小鼠相比，体重较轻且寿命较短。在电子显微镜下，12月龄的SMP30Y/-小鼠的肝细胞中明显含有许多脂滴、线粒体异常肿大且嵴不清晰，以及充满电子致密体的溶酶体肿大，而野生型小鼠的肝细胞则没有这些现象。在SMP30Y/-小鼠的肝脏标本中，随着动物年龄的增长，中央静脉周围可见的脂滴数量显著增加，其大小和数量都明显增多。对SMP30Y/-小鼠的中性脂质、肝脏总甘油三酯和胆固醇进行生化分析，结果显示其水平分别比年龄匹配的野生型小鼠高约3.6倍和3.3倍。此外，SMP30Y/-小鼠肝脏总磷脂的值比其野生型对应物高约3.7倍。通过薄层色谱分析，在SMP30Y/-小鼠肝脏的脂质提取物中分别检测到磷脂酰乙醇胺、心磷脂、磷脂酰胆碱、磷脂酰丝氨酸和鞘磷脂的积累，这些结果有力地表明SMP30缺陷对这些中性脂质和磷脂代谢有深远影响。可以想象，这种脂质代谢异常足以缩短SMP30缺陷小鼠的寿命。
