{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Poudel SB"],"funding":["NIA NIH HHS","NIDDK NIH HHS","NIEHS NIH HHS"],"pagination":["3027-3042"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12181575"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["47(3)"],"pubmed_abstract":["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<sub>12-24</sub> 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<sub>12-24</sub> mice, evidenced by GFAP<sup>+</sup> (glial fibrillary acidic protein, a marker of astrocytes) and Iba-1<sup>+</sup> (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<sub>12-24</sub> 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."],"journal":["GeroScience"],"pubmed_title":["The impact of inactivation of the GH/IGF axis during aging on healthspan."],"pmcid":["PMC12181575"],"funding_grant_id":["R01 AG059779","P30 DK020572","R01 ES033171","RF1 AG078170"],"pubmed_authors":["Manchanayake DH","Yakar S","Jayarathne H","Basta-Pljakic J","Dixit M","Ruff RR","Yildirim G","He Z","Schaffler MB","Kopchick JJ","Poudel SB","Duran-Ortiz S","Sadagurski M"],"additional_accession":[]},"is_claimable":false,"name":"The impact of inactivation of the GH/IGF axis during aging on healthspan.","description":"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<sub>12-24</sub> 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<sub>12-24</sub> mice, evidenced by GFAP<sup>+</sup> (glial fibrillary acidic protein, a marker of astrocytes) and Iba-1<sup>+</sup> (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<sub>12-24</sub> 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.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jun","modification":"2026-06-01T07:59:41.722Z","creation":"2026-04-08T10:43:47.331Z"},"accession":"S-EPMC12181575","cross_references":{"pubmed":["39535693"],"doi":["10.1007/s11357-024-01426-3"]}}