Table 1.
Phenotypic characteristics of mice with mutations affecting the GH-IIS axis and lifespan
| Mice models | Key Physiology | Average Lifespan (%) | Body weight (%) | Body fat | Insulin sensitivity | Tumor incidence | Stress resistance | Plasma GH | Plasma IGF1 | Plasma glucose | References |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Long-lived models | |||||||||||
| Snell (Pou1f1−/−) | GH, PRL and TSH deficiency | F+51 M+29 (11718806) | ↓ (25–33) | ↑ | ↑ | ↓ | ↑ | ↓ | ↓ | ↓ | 16577229 1371619 |
| F and M+38 (15699523) | 11718806 | ||||||||||
| 15699523 | |||||||||||
| Ames (Prop1−/−) | GH, PRL and TSH deficiency | F+68 M+49 (8900272) | ↓ (33) | ↑ | ↑ | ↓ | ↑ | ↓ | ↓ | ↓ | 8900272 11719795 |
| F and M+37 (11719795) | |||||||||||
| Little (Ghrhr−/−) | GH deficiency | F+25 M+23 (11371619) | ↓ (50–67) | ↑ | ↑ | ↓ | ↑ | ↓ | ↓ | ↓ | 1270792 11371619 |
| Ghr−/− | GH resistance | F+38 M+55 (10875265) | ↓ (41–50) | ↑ | ↑ | ↓ | ↑ | ↑ | ↓ | ↓ or ↔ | 10875265 |
| F+25 M+16 (12933651) | 12933651 | ||||||||||
| F+30 M+30 (16682650) | 16682650 | ||||||||||
| Fgf21 Tg* | GH resistance | F+40 M+30 (23066506) | ↓ (60) | ↔ | ↑ | ? | ? | ↑ | ↓ | ↓ | 18585098 |
| 23066506 | |||||||||||
| LI-Igf1−/− | IGF1 reduction 75–85% | F+16 (21799924) | ↓ (75–100) | ↓ | ↓ | ? | ? | ↑ | ↓ | ↔ | 10359843 |
| 11423474 | |||||||||||
| 21799924 | |||||||||||
| Heart Igf1 Tg* | IGF1 excessed | M+23a (17973971) | ↔ (100) | ? | ? | ? | ? | ? | ↑ | ↔ | 17973971 |
| Pappa−/− | IGF1 reduced | F and M+38 (17681037) | ↓ (40) | ? | ↔ | ↓ | ? | ↔ | ↔ | ↔ | 14973274 |
| F+29 M+24 (20351075) | 17681037 | ||||||||||
| 20351075 | |||||||||||
| Klotho Tg | IIS inhibition | F+19 M+31 (16123266) | ↔ (100) | ? | F ↔ | ? | ↑ | ? | ? | ↔ | 16123266 |
| F+19 M+20 (16123266) | M↓ | ||||||||||
| Igf1r+/− | IGF1 resistance | F+33 M NS (12483226) | ↓ (90) | ? | ↓ | ↔ | ↑, F ↑ M | ? | ↔ | ↔ | 12483226 |
| F and M NS (22132081) | ↔ | 22132081 | |||||||||
| Brain IGF1R+/−* | Brain IIS reduction | F+8 M+13b (18959478) | ↓ (90–92) | ↑ | ↓ | ↓ | ↑ | ↓ | ↓ | ↔ | 18959478 |
| FIR−/− | Fat-specific insulin resistance | F and M+11 (12543978) | ↓ (70) | ↓ | ↑ | ? | ? | ? | ? | ↔ | 12110165 |
| 12543978 | |||||||||||
| Irs1−/−* | Insulin resistance or normal | F+16 M+14 (21283571) | ↓ (70) | ↓ | ↓ | ? | ? | ↔ | ↔ | ↔ | 7969452 17928362 |
| 21283571 | |||||||||||
| 29779018 | |||||||||||
| Irs2+/− | IRS2 reduced | F and M+17 (17641201) | ↔ (100) | ? | ↑ or ↔ | ? | ? | ↔ | ↔ | ↓ | 17641201 |
| F and M NS (17928362) | 17928362 | ||||||||||
| Brain Irs2+/− | Brain IRS2 reduced | F and M (+/−)+18 (17641201) | ↔ (100) | ↑ | ↓ | ? | ? | ↔ | ↔ | ? | 17641201 |
| Brain Irs2−/− | F and M (−/−)+14 (17641201) | ||||||||||
| mtor+/−::mlst8+/−* | mTORC1 reduction 50% | F+14 M NS (22461615) | ↔ (100) | ? | ↔ | ? | ? | ? | ? | ↔ | 22461615 |
| S6K1−/−* | S6K1 deficient | F+20 M NS (19797661) | ↓ (48) | ↓ | ↑ | ? | ? | ↔ | ↔ | ↔ | 19797661 |
| p66Shc+/− | IRS inhibition, S6K1 inhibition | F and M (+/−)+7a (10580504) | ↔ (100) | ↓ | ↔ | ? | ↑ | ? | ? | ↔ | 10580504 |
| p66Shc−/− | F and M (−/−)+28a (10580504) | 20624962 | |||||||||
| Myc+/−* | IGF1 reduction and MYC-regulated genes | F+21 M+11a (25619689) | ↓ (81) | ↔ | ? | ↔ | ? | ? | ↓ | ? | 25619689 |
| Normal or short-lived models | |||||||||||
| GHA Tg | GH resistance | NS (12933651) | ↓ (55–70) | ↑ | ↑ | ↓ | ? | ? | ↓ | ↓ or ↔ | 1791834 11487276 |
| 12933651 | |||||||||||
| 15231300 | |||||||||||
| Bovine GH Tg | GH excessed | M-45 (14583653) | ↑ (200) | ↓ | ↓ | ↑ | ? | ↑ | ↑ | ↓ | 1791834 11701438 |
| 14583653 | |||||||||||
| 15231300 | |||||||||||
| 18948397 | |||||||||||
| LID | 75% reduced IGF1 | M-? (22421704) | ↔ (100) | ↑ | ↓ | ↓ | ? | ↑ | ↓ | ↔ | 10377413 |
| 11334415 | |||||||||||
| 22421704 | |||||||||||
| Kl−/−* | IIS activation, growth retardation | 60.7 daysc (9363890) | ↓ (44–47) | ? | ↓ | ? | ? | ? | ? | ? | 9363890 |
| Irs2−/− | Irs2 deletion | F-26 M-84 (9495343) | ↓ (90) | ? | ↓ | ? | ? | ? | ? | ↑ | 9495343 |
*
New added or updated mice models in this review.
↑ up-regulated; ↓ down-regulated; ↔ no difference; ?, no data available.
a
Median lifespan.
b
Significant at censored lifespan data before week 130–135.
c
No lifespan data for control.
NS, not significant.