Do DHEA-S and IGF-1 decline with age?

During aging, the endocrine system undergoes a coordinated shift characterized by the decline of two primary anabolic signals: dehydroepiandrosterone sulfate (DHEA-S) and insulin-like growth factor 1 (IGF-1). This decline marks a systemic transition toward a less regenerative physiological state.

Clinical decline and axis tone

• DHEA-S and Adrenal Output: DHEA-S levels peak in the third decade of life and decline progressively by 2% to 5% per year (20% to 40% per decade), leaving older adults with only 10% to 20% of their youthful peak. This decline directly tracks reduced adrenal androgen secretory reserve.
• IGF-1 and Somatotropic Tone: Circulating IGF-1 levels fall by approximately 14% per decade of adult life, resulting in older adults having levels that are 30% to 50% of their youthful peak. This reduction directly reflects a blunting of growth hormone (GH) axis tone, commonly referred to as somatopause.

Mechanistic pathways and cellular repair

• Anabolic Signaling: IGF-1 directly stimulates muscle protein synthesis, osteoblast-driven bone remodeling, and neurovascular maintenance. Simultaneously, DHEA-S serves as an intracrine prohormone for local conversion to active androgens and estrogens, which supports protein synthesis and counteracts catabolic cortisol.
• Inflammatory Modulation: Beyond direct repair, DHEA-S modulates the systemic microenvironment by suppressing pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha), helping to maintain an anti-inflammatory, tissue-regenerative state.

Bottom line

• Key Takeaway: Lower levels of DHEA-S and IGF-1 serve as reliable clinical indicators of reduced adrenal secretory reserve and blunted somatotropic tone. Together, these declines shift the body's endocrine balance away from cellular repair and toward a catabolic, pro-inflammatory environment that accelerates tissue degradation.