Insulin resistance, aging biology, and non- communicable chronic diseases: a narrative review of bidirectional mechanisms and translational implications.
Level 5 - mechanism / opinion, no new human data
Narrative review synthesizing mechanistic and observational literature without systematic review methodology.
PubMed 42577545 · doi:10.3389/fendo.2026.1891078
What was done
Authors conducted a structured narrative literature review synthesizing mechanistic, translational, omics, epidemiologic, and intervention studies. The review evaluated bidirectional relationships between insulin resistance, compensatory hyperinsulinemia, biological aging processes, and age-related non-communicable chronic diseases such as cardiovascular disease, neurodegenerative disorders, sarcopenia, chronic kidney disease, and liver disease.
What was found
The abstract reports no quantitative values or effect estimates. It outlines reciprocal mechanistic pathways connecting insulin resistance to aging biology, including insulin/IGF-1 signaling disruption, mitochondrial dysfunction, oxidative stress, endothelial dysfunction, adipokine imbalance, chronic inflammation (inflammaging), cellular senescence, ectopic lipid accumulation, AGE-RAGE signaling, and impaired autophagy and proteostasis. The authors note that evidence quality ranges from strong to exploratory and that most published clinical associations currently lack demonstrated causality.
Why it matters
The paper frames insulin resistance as an integrated, bidirectional mediator within a broader network of metabolic and biological aging mechanisms rather than a standalone, unidirectional cause of age-related chronic disease.
Limits
As a narrative review, the paper lacks systematic search criteria, explicit inclusion/exclusion protocols, and formal risk-of-bias assessment. Much of the underlying evidence discussed remains associative or preclinical, with limited established causal evidence in human clinical settings.
Cited by
- supports Insulin resistance is a causal driver of systemic endothelial dysfunction and cardiovascular dysfunction.