Effect of aging on expression of angiogenesis-related factors in mouse skeletal muscle.

The molecular mechanisms by which capillary supply is maintained with advancing age remain to be elucidated. To help clarify these mechanisms, we investigated the gene expression levels of angiogenesis-related factors in young (2.5-month-old), adult (6-month-old), and old (22-month-old) mice. To assess the capillary supply, the capillary endothelium in frozen transverse sections was identified by staining for alkaline phosphatase. The mRNA levels for angiogenesis-related factors were analyzed using real-time RT-PCR. The capillary supply to individual muscle fibers, assessed as the number of capillaries around a muscle fiber, did not change with advancing age. Real-time RT-PCR analysis showed that (1) the level of mRNA for VEGF was lower in old animals than young animals; (2) the mRNA levels of Flt-1 and neuropilin-1 are lower in old animals than young animals, while that of KDR/Flk-1 remained unchanged with advancing age; and (3) the levels of mRNA for angiopoietin-1 and -2 remained unchanged, while the mRNA for Tie-2 was lower in old animals than young animals. These findings suggest that capillary supply is maintained irrespective of the down-regulation of several angiogenesis-related factors and that old animals possess the minimum levels of maintenance and reparative abilities needed to preserve the capillary supply.