Table 1.
Physiologic Parameters of IGF-1 Deficient and Wild-Type Mice Related to IGF-1 Function
| IGF-1 Levels | ||||
|---|---|---|---|---|
| Genotype | Liver | Kidney | Muscle | Serum |
| IGF-1 deficient | 1980±555ng/g | 1620±208ng/g | 678±181ng/g | 480±58ng/mL |
| Wild type | 2808±245ng/g | 2396±434ng/g | 1541±706ng/g | 909±123ng/m |
| Organ Weight (g) | ||||
| Genotype | Liver | Kidney | Heart | Brain |
| IGF-1 deficient | 1.37±0.001 | 0.21±0.007 | 0.155±0.0015 | 0.44±0.028 |
| Wild type | 1.39±0.002 | 0.21±0.022 | 0.22±0.0033 | 0.47±0.019 |
| Organ Weight (% of body weight) | ||||
| Genotype | Liver | Kidney | Heart | Brain |
| IGF-1 deficient | 7.3% | 1.1% | 0.8% | 2.4% |
| Wild type | 6.3% | 0.9% | 1.0% | 2.1% |
| Organ Weight/Tibia Length (g/cm) | ||||
| Genotype | Liver | Kidney | Heart | Brain |
| IGF-1 deficient | 1.41 | 0.175 | 0.129 | 0.367 |
| Wild type | 1.06 | 0.161 | 0.169 | 0.361 |
| Litter Size | ||||
| IGF-1 deficient | 6±2 | |||
| Wild type | 8±2 | |||
| Bone Mineral Density | ||||
| 100 d | 495 d | |||
| Male | Female | Male | Female | |
| IGF-1 deficient | 0.0425g/cm2 | 0.0475g/cm2 | 0.0435g/cm2 | 0.0440g/cm2 |
| ±0.002 | ±0.002 | ±0.002 | ±0.002 | |
| Wild type | 0.0535g/cm2 | 0.0565g/cm2 | 0.0525g/cm2 | 0.0535g/cm2 |
| ±0.002 | ±0.002 | ±0.002 | ±0.002 | |
| End-of-Life Pathology | ||||
| Male | Female | |||
| Wild Type (N = 26) | IGF-1 Deficient (N = 6) | Wild Type (N = 26) | IGF-1 Deficient (N = 12) | |
| Cause of death | ||||
| Neoplastic | 15 (57.7%) | 2 (33.3%) | 15 (57.7%) | 6 (50.0%) |
| Lymphoma | 1 | 1 | 1 | 4 |
| Hemangioma | 9 | 0 | 9 | 1 |
| Hepatocellular carcinoma | 2 | 1 | 2 | 1 |
| Others | 3 | 0 | 3 | 0 |
| Non-neoplasm | 5 | 2 | 5 | 3 |
| Glomerurosclerosis | 4 (26.7%) | 1 (16.7%) | 4 (26.7%) | 3 (25%) |
| Thrombus, heart | 1 | 1 | 1 | 0 |
| Other | 6 | 2 | 6 | 3 |
| Total | 26 | 6 | 26 | 12 |
Note: IGF-1 = IGF type 1.
Physiological parameters predicted to be influenced by changes in IGF-1 levels were examined in wild-type and IGF-1-deficient mice.
Total IGF-1 levels were assessed by ELISA using extracts from the tissues indicated or using serum in female mice. Tissue IGF-1 levels were examined in two separate assays with similar results, whereas serum IGF-1 levels presented are representative of at least three similar assays; animal numbers were n = 4 for kidney, n = 5 for liver and muscle, n = 15 for IGF-1-deficient serum, and n = 4 for wild-type serum. Absolute values of IGF-1 levels varied between assays, whereas relative differences between wild-type and IGF-1-deficient animals remained consistent. All differences between wild-type and IGF-1-deficient animals were significant at p < .05.
Average body weights were 18.62 g for IGF-1-deficient females and 22 g for control females at 7 months of age. Tibia length at this age was 1.2cm for IGF-1 deficient and 1.3 for controls.
Litter size was determined during breeding for longevity cohorts. Organ weight was examined at 3 months of age during necropsy. Organs were washed in phosfate-buffered saline and briefly dried prior to weighing, n = 4 for each genotype.
Bone mineral density was assessed by dual-energy x-ray absorptiometry; bone mineral density was lower (p < .0001) in the IGF-1-deficient mice compared with controls. Bone mineral density was reduced at 495 days relative to 100 days, and sex also influenced bone mineral density (p < .01); n = 10 in each age group and for each sex.
Pathological examination was performed at the University of Texas Health Sciences Center on a subset of animals from the Lankenau Cohort.
The mean and maximum life span achieved for the IGF-1-deficient and control mice at each institution is presented. The data labeled “All Cohorts” contains life-span data from all mice at all three institutions. Maximum life span represents the average life span of the final 10% of each cohort. The maximum life-span difference between IGF-1-deficient and control animals at all sites is significant at p = .0001 for males and p = .0016 for females.