# Hyperfunction theory of aging

The hyperfunction theory of aging was proposed by Mikhail Blagosklonny in 2006. It offers a different cause of aging. It says aging is driven by growth pathways that stay overactive. The main culprit is mTOR. The alternative view (passive damage piling up) takes a back seat. During development, these pathways are essential for growth and reproduction. The catch: after you finish developing, they are never switched off. That creates a 'quasi-program', a pointless continuation of the growth program. Evolution never selected against it, because harm after reproduction carries no fitness penalty. This cellular 'hyperfunction' has consequences. It drives cellular senescence, tissue overgrowth, fibrosis, and sterile inflammation. Those, in turn, produce classic age-related diseases. The theory does not deny that molecular damage accumulates. It just argues that mTOR-driven hyperfunction limits life first, before damage alone would. The support is concrete. In rodent studies, rapamycin extended lifespan even when started late in life (Harrison et al., 2009). And a randomized trial (Mannick et al., 2014) found that low-dose everolimus improved flu-vaccine response in older adults. Whether mTOR inhibition extends lifespan in healthy humans is still open. The PEARL trial gave preliminary safety and healthspan data in 2024. But there is no definitive outcome evidence as of 2025.

## Sources

- Blagosklonny MV. (2006). Aging and Immortality: Quasi-Programmed Senescence and Its Pharmacologic Inhibition. Cell Cycle. https://doi.org/10.4161/cc.5.18.3288
- Blagosklonny MV. (2021). The hyperfunction theory of aging: three common misconceptions. Oncoscience. https://doi.org/10.18632/oncoscience.545
- Barzilai DA. (2025). Mikhail 'Misha' Blagosklonny's enduring legacy in geroscience: the hyperfunction theory and the therapeutic potential of rapamycin. Aging. https://doi.org/10.18632/aging.206189
- Mannick JB, Del Giudice G, Lattanzi M, et al.. (2014). mTOR inhibition improves immune function in the elderly. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.3009892

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