Journal September 26, 2026 5 min read

How the IGF-1 axis changes with age

IGF-1 signalling declines across the lifespan, but the trajectory is not linear and differs by tissue, diet and disease state. This page summarises what the current registered and published evidence shows about age-relat

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Insulin-like growth factor 1 (IGF-1), also called somatomedin C, is a 70-amino-acid single-chain polypeptide hormone of the somatomedin family, structurally homologous to proinsulin and acting largely through the type 1 IGF receptor (IGF-1R), a receptor tyrosine kinase. Circulating IGF-1 is produced mainly in the liver under growth hormone (GH) control, and is bound in serum by IGF-binding proteins, principally IGFBP-3. The work described below centres on the GH/IGF-1 somatotropic axis and its receptor family.

Across the human lifespan, serum IGF-1 is low in infancy, rises through childhood and puberty to a peak in late adolescence, then falls progressively through adulthood. The decline is not uniform: it varies with nutritional status, body composition, sex, and the presence of metabolic or endocrine disease, and it is accompanied by changes in IGFBP-3 that alter the amount of free, receptor-available hormone. The sections below set out what specific studies have measured.

Research Studies

IGF-1 and age in healthy children: the AgRP/GH axis study

A registered cross-sectional study is measuring plasma levels of Agouti-related peptide (AgRP) in 140 healthy children aged 5–17 years and relating those levels to GH, IGF-1, age, body composition and other endocrine parameters [1]. The rationale given is that GH stimulates AgRP and that AgRP may mediate some of GH's nutritional and metabolic effects, supporting the concept of a GH–AgRP axis [1]. The study is designed to characterise plasma AgRP in children for the first time and to determine how it relates to IGF-1 across this age band [1].

IGF-1 and age in children on different diets

A study of 7,344 serum samples from 2,508 healthy participants aged 3 months to 19 years compared IGF-1 and IGFBP-3 concentrations and anthropometry between omnivorous, vegetarian and vegan children, using optimal 1:3 pair matching from age 10 [4]. After adjustment for pubertal status, vegan children were shorter than vegetarians (β = −0.59, p = 0.006) [4]. The same dataset provides age-stratified IGF-1 and IGFBP-3 values across the paediatric range, which is the relevant comparison for anyone assessing how the axis changes with age in this population [4].

IGF-1 in adults with type 2 diabetes and MASLD

A 3-month, single-centre, prospective, randomised, parallel-controlled, open-label trial is investigating the effect of metformin combined with dapagliflozin on serum IGF-1 in male patients with type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease [2]. Eighty-four eligible male patients aged 30–60 years, with HbA1c 7.0–10.0%, CAP ≥248 dB/m, and on stable metformin monotherapy for at least 8 weeks, are randomised 1:1 to continue metformin alone or to receive metformin plus dapagliflozin 10 mg/day for 12 weeks [2]. The primary endpoint is the change in serum IGF-1 from baseline to 3 months between groups [2]. This is a disease-state population, not a healthy-ageing one, and the results are not yet reported.

IGF-1 axis biomarkers and growth response in paediatric growth disorders

A systematic scoping review of PubMed-indexed literature from 2000 to 2026 examined precision medicine in paediatric growth disorders, integrating clinical phenotype, genetics, IGF-1 biology and artificial intelligence [6]. The review notes that recombinant human growth hormone has been used for four decades under a largely population-based dosing paradigm, yet growth response varies substantially among children with apparently similar auxological phenotypes [6]. IGF-1 axis biomarkers are among the variables proposed to explain that variability [6].

MC4R variation and somatropin response in severe GH deficiency

A case report described pharmacogenetic hypersensitivity to somatropin in a child with severe growth hormone deficiency and an MC4R p.V166I variant [7]. MC4R is a G protein-coupled receptor regulating energy homeostasis; pathogenic MC4R variants are the most common cause of monogenic obesity and are frequently associated with increased linear growth [7]. The report concerns the link between MC4R signalling and somatic growth in a single paediatric patient [7].

GH receptor antagonism and IGF-1 in acromegaly models

Acromegaly is caused by GH hypersecretion from a pituitary adenoma, and pegvisomant is the only approved GH receptor antagonist, given by daily subcutaneous injection [5]. A novel half-life-extended monoclonal antibody GH receptor antagonist, MAR002, was generated by immunising transgenic mice with the extracellular domain of human and cynomolgus monkey GH receptor and engineering Fc modifications to limit effector function and extend serum half-life [5]. MAR002 was benchmarked against pegvisomant in biophysical assays and cellular signalling inhibition studies [5]. This work is preclinical and animal- and cell-based; it does not establish human dosing or outcomes.

Exercise, IGF-1 biology and colon cancer outcomes

The phase III CHALLENGE trial found that a 3-year structured physical activity programme significantly improved disease-free survival (HR 0.72) and overall survival (HR 0.63) in patients with resected colon cancer [3]. A review synthesising the clinical, epidemiological and translational evidence describes exercise as a validated, disease-modifying intervention in this population [3]. The review places IGF-1 axis biology among the translational mechanisms considered, alongside other systemic mediators [3].

Diabetes, IGF-1 and cancer risk

A review of epidemiological and molecular-mechanism studies examined the association between diabetes mellitus and cancer risk [8]. Diabetes and cancer are described as two major global health burdens, and the review systematically analyses recent advances in the relationship between them [8]. IGF-1 signalling is among the molecular pathways discussed in that context [8].

Comparison of age-related IGF-1 findings across the cited studies

Study / population	Age range	IGF-1-related measure	Direction reported
AgRP/GH axis study, healthy children [1]	5–17 years	Plasma AgRP vs GH, IGF-1, age	Relationship under investigation
Dietary cohort, healthy children [4]	3 months–19 years	IGF-1 and IGFBP-3 serum concentrations	Vegan children shorter than vegetarians after pubertal adjustment (β = −0.59, p = 0.006)
Metformin–dapagliflozin trial, male T2DM with MASLD [2]	30–60 years	Change in serum IGF-1 at 3 months	Primary endpoint; results not yet reported
Paediatric growth disorder review [6]	Children	IGF-1 axis biomarkers vs growth response	Response varies among similar phenotypes
Acromegaly preclinical work [5]	Transgenic mice, cell assays	GHR antagonism and downstream signalling	Preclinical only

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