{"doi":"10.18632/aging.204257","title":"Looking at IGF-1 through the hourglass","abstract":"The role of insulin-like growth factor 1 (IGF-1) in human aging has been hotly debated.IGF-1, a central regulator of growth, plays a critical function in development and energy investment.For instance, the absence of functional IGF-1 or IGF-1 receptors in the central nervous system leads to severe developmental abnormalities, whereas reduction in circulating IGF-1 level, which is regulated by growth hormone (GH), results in small whole-body size [1].In contrast, during aging, circulating IGF-1 may become dispensable or even detrimental.In fact, reduced long-term GH/IGF-1 improves the lifespan and health of numerous model organisms, including nematode worms, fruit flies, and mice.Despite strong evidence for beneficial effects of diminished GH/IGF-1 signaling in aging models, human studies investigating IGF-1's role in aging and age-associated diseases have been discrepant and until recently it has not been possible to reconcile the inconsistent results.Extreme phenotypes in humans can shed some light on the controversy.Acromegaly and Laron dwarfism provide examples of medical conditions resulting from extreme excess or insufficiency of IGF-1, respectively.The excess GH and IGF-1 of acromegaly cause a variety of harmful effects, including hypertension, diabetes, cardiac dysfunction, colonic polyps, and arthritis; all of these can be classified as conditions that become more prevalent with aging.In contrast, the attenuated IGF-1 signaling that results from defective GH receptors of Laron dwarves seems to confer protection from cancer, stroke, and diabetes while increasing obesity and auditory deficits.Thus, it appears that exceptionally high circulating levels of IGF-1 are generally harmful, while extremely low IGF-1 signaling results in a combination of benefits and harms.However, direct study of cohorts with more modest variability in circulating IGF-1 levels has yielded conflicting results.While some previous studies, including ours, have shown a positive association between high IGF-1 and adverse outcomes in respect to mortality and age-related co-morbidities [2, 3], others have found the opposite effect or no associations [4].These prior studies were generally conducted in modestly-sized samples and varied significantly in the basic demographics of the participants.Nonetheless, one pattern did begin to emerge from these diverse studies: the beneficial effects of lower IGF-1 were most apparent among the oldest age groups.Thus, it became","journal":"Aging","year":2022,"id":285323,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9566,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":280514,"name":"Sofiya Milman","orcid":"0000-0001-9247-0082","position":1,"is_corresponding":false},{"id":311483,"name":"William B. Zhang","orcid":"0000-0002-4372-5496","position":0,"is_corresponding":true}],"reference_count":8,"raw_metadata":null,"created_at":"2026-07-19T00:29:40.826853Z","pmid":"36063137","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}