IGF-1 Signaling (Insulin/IGF-1 -> PI3K -> AKT axis)

Classification

Category: Upstream regulator (growth-factor signaling axis)

Aliases: Insulin/IGF-1 signaling (IIS), Insulin-like growth factor 1 signaling

Relationship to mTOR complexes: Upstream of mTORC1 (via PI3K-AKT-TSC1/2-Rheb) — see mTORC1 vs mTORC2 for the full complex-level map.

Summary

Insulin and IGF-1 binding to their receptors activates PI3K, which activates AKT, which inhibits TSC1/2, which activates Rheb, which activates mTORC1. This is the canonical growth-factor input branch of mTORC1 regulation, distinct from the amino-acid (Rag) and energy-status (AMPK) branches. IMPORTANT editorial nuance from the sourcing brief: IGF-1 is NOT a one-directional 'lower is always better' longevity score -- both excess and deficiency states have documented trade-offs in the source literature, and this dataset does not endorse a simple 'minimize IGF-1' framing.

• Circulating insulin and IGF-1 bind their respective receptors, activating receptor tyrosine kinase signaling
• Downstream PI3K activation phosphorylates and activates AKT

• Activated AKT inhibits TSC1/2, activating Rheb and thereby mTORC1 (see /akt, /tsc1-tsc2, /rheb)
• Lower circulating IGF-1 was associated with longest lifespan in the Solon-Biet low-protein/high-carbohydrate diet groups (see /protein-restriction) -- an association, not established as a standalone causal lifespan lever

• IGF-1 signaling is the growth-factor branch that converges with the amino-acid (Rag GTPase) and energy-status (AMPK) branches at the TSC1/2-Rheb node to jointly control mTORC1.
• Editorial nuance (brief §4): IGF-1 is not a one-directional lifespan score. Both very high and very low IGF-1 states carry documented trade-offs in the literature; this dataset reports the Solon-Biet low-IGF-1/long-lifespan association without endorsing a general 'lower IGF-1 is always better' claim.

Source tier

Tier 2 · Biological synthesis (author-cluster reviews, not primary trial data) Reference synthesis attributed in the brief to the Saxton & Sabatini; Laplante & Sabatini; and Liu & Sabatini mTOR review literature (author-cluster attribution, tier 2, brief §4). Exact article-level PMID/DOI not supplied in the sourcing brief and is not fabricated here.