Lifelong congenital untreated isolated GH deficiency does not alter human leukocyte telomere length

Background Telomere shortening reflects cumulative cell replication and functions as a mitotic clock. It is influenced by age and body mass, as both increase the demand for cell proliferation. The GH/IGF-I axis plays a central role in cell proliferation. The Itabaianinha cohort in Brazil, with severe isolated congenital GH deficiency (IGHD) due to a homozygous mutation in the GHRH receptor gene (GHRHR), represents a unique human model of markedly reduced stature and body mass with preserved lifespan, extended healthspan, and normal brain aging. Purpose To evaluate leukocyte telomere length (LTL) in individuals with untreated congenital IGHD and its association with the GH/IGF axis and metabolic parameters. Methods LTL was assessed in 34 IGHD subjects homozygous for the GHRHR c.57 + 1G→A mutation (aged 24–89 years) and 36 controls homozygous for the wild-type allele (aged 26–79 years). LTL was measured by quantitative PCR using the telomere-to-single copy gene (T/S) ratio. T/S ratio Z-scores used the control-group mean and standard deviation. Circulating IGF-I, IGF-II, and metabolic parameters were evaluated. Results IGHD subjects had markedly reduced height and weight, while BMI was similar between groups. IGF-I and IGF-II levels were significantly lower in IGHD ( p < 0.0001 for both). LTL did not differ between IGHD,0.96 (0.3), and controls),1.01 (0.4), and age-related telomere decline was comparable. Z-scores confirmed no deviation from expected values. LTL correlated modestly with IGF-II, but not with IGF-I or HOMA-IR. Conclusion LTL in individuals with untreated IGHD was like that of controls. Age-related LTL decline was also comparable between the groups.