Blocking growth hormone in midlife extends mouse lifespan

Growth hormone drives the production of IGF-1, a growth factor that is useful early in life but is associated with accelerated aging at chronically high levels in later life. Humans born insensitive to growth hormone (Laron syndrome) show striking resistance to diabetes, cognitive decline, and cardiovascular disease. Earlier mouse studies confirmed that animals with permanently reduced growth hormone signaling live longer, but those models were altered from birth, disrupting normal growth and development.

Intervening at midlife

The researchers developed a mouse model in which the growth hormone receptor (GHR) is knocked out at 12 months of age, roughly equivalent to human middle age. Males became shorter and lighter but outlived controls. Females showed no change in body weight yet also lived longer. The effect was most pronounced among the longest-lived animals: the longest-lived female GHR knockout mice survived four months beyond the longest-lived female controls. The study was published in the journal Aging Cell.

The role of IGF-1

Both sexes developed increased fat mass and reduced lean mass compared with controls. Under ordinary circumstances those changes would signal metabolic trouble. Yet inflammatory markers were largely unaffected and the animals remained mobile and active throughout. IGF-1 levels dropped sharply in males after the receptor was switched off. The researchers note that this pattern differs substantially from typical age-related obesity.

From a longevity perspective, a midlife intervention avoids the developmental problems caused by early-life disruption of growth hormone signaling. Whether comparable effects occur in humans remains unknown. The findings are preliminary and based on a mouse model. They do, however, point toward growth hormone receptor blockade as a potential direction for future anti-aging research.

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