| First Author | Poudel SB | Year | 2025 |
| Journal | Geroscience | Volume | 47 |
| Issue | 3 | Pages | 3027-3042 |
| PubMed ID | 39535693 | Mgi Jnum | J:389116 |
| Mgi Id | MGI:8385146 | Doi | 10.1007/s11357-024-01426-3 |
| Citation | Poudel SB, et al. (2025) The impact of inactivation of the GH/IGF axis during aging on healthspan. Geroscience 47(3):3027-3042 |
| abstractText | Several mouse lines with congenital growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis disruption have shown improved health and extended lifespan. The current study investigated how inactivating this axis, specifically during aging, impacts the healthspan. We used a tamoxifen-inducible global GH receptor (GHR) knockout mouse model starting at 12 months and followed the mice until 24 months of age (iGHRKO(12-24) mice). We found sex- and tissue-specific effects, with some being pro-aging and others anti-aging. Measuring an array of cytokines in serum revealed that inactivation of the GH/IGF-1 axis at 12 months did not affect systemic inflammation during aging. On the other hand, hypothalamic inflammation was significantly reduced in iGHRKO(12-24) mice, evidenced by GFAP(+) (glial fibrillary acidic protein, a marker of astrocytes) and Iba-1(+) (a marker for microglia). Liver RNAseq analysis indicated feminization of the male transcriptome, with significant changes in the expression of monooxygenase, sulfotransferase, and solute-carrier-transporter gene clusters. Finally, we found impaired bone morphology, more pronounced in male iGHRKO(12-24) mice and correlated with GH/IGF-1 inactivation onset age. We conclude that inhibiting the GH/IGF-1 axis during aging only partially preserves the beneficial healthspan effects observed with congenital GH deficiency. |
