Do low DHEA-S and low IGF-1 indicate reduced anabolic tone?

In aging men, the gradual decline of key endocrine axes shifts the physiological balance toward a catabolic state, reducing overall physical resilience and metabolic health.

Clinical and metabolic impacts of low DHEA-S

• Marker of Adrenal Tone: Serum DHEA-S is the primary circulating adrenal androgen and serves as a direct biomarker of adrenal anabolic output.
• Muscle and Fat Distribution: Lower endogenous DHEA-S levels in aging males independently predict decreases in handgrip strength, calf muscle area, and skeletal muscle mass.
• Metabolic Resilience: While DHEA supplementation trials show modest improvements in lean mass (averaging approximately 0.45 kg), restoring DHEA-S levels in overweight older adults with impaired glucose tolerance significantly reduces visceral abdominal fat and improves insulin sensitivity indices.

Molecular mechanisms and GH-IGF-1 decline

• The Somatopause Axis: Circulating IGF-1 is the primary downstream mediator of growth hormone (GH). Its age-related decline reflects reduced GH anabolic tone.
• Impaired AKT-mTOR Signaling: Diminished IGF-1 levels limit the activation of the downstream IRS-PI3K-AKT-mTOR signaling cascade in skeletal muscle. This molecular deficit compromises muscle protein synthesis, satellite cell proliferation, and regenerative capacity.
• Functional Consequences: This signaling decline clinically manifests as muscle wasting (sarcopenia), loss of muscle strength, compromised bone density from reduced osteoblast differentiation, delayed tissue healing, and systemic fatigue.

Bottom line

• Low DHEA-S and IGF-1 are reliable biological indicators of reduced adrenal and growth-hormone anabolic tone. This hormonal decline collectively impairs critical metabolic pathways and downstream skeletal AKT-mTOR signaling, undermining lean muscle preservation, tissue repair, and metabolic resilience in aging males.