Will you live to 120? · Sources and Further Reading

Chapter 6 — Proteostasis

Trifunovic, A., et al. (2004). Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature. — and Kujoth, G.C., et al. (2005). Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science. — The mutator mouse: premature aging from mtDNA mutations, but without the runaway ROS the theory predicted.

Andziak, B., et al. (2006). High oxidative damage levels in the longest-living rodent, the naked mole-rat. Aging Cell. — The wrinkled refutation of “oxidative damage sets lifespan.”

Schriner, S.E., et al. (2005). Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. — The modest exception that proves how disappointing the antioxidant-overexpression experiments mostly were.

Andreux, P.A., et al. (2019). The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nature Metabolism. — The shift from “mop up ROS” to “improve quality control.”

Chapter 6 — Proteostasis

Anfinsen, C.B. (1973). Principles that govern the folding of protein chains. Science. — The Nobel lecture: structure is encoded in sequence.

Levinthal, C. (1969). How to fold graciously. (In Mössbauer Spectroscopy in Biological Systems, proceedings.) — The paradox of folding speed.

Hartl, F.U., Bracher, A., & Hayer-Hartl, M. (2011). Molecular chaperones in protein folding and proteostasis. Nature. — The chaperone machinery, reviewed.

Ohsumi, Y. (2014). Historical landmarks of autophagy research. Cell Research. — Autophagy from its discoverer (2016 Nobel laureate).

Prusiner, S.B. (1982). Novel proteinaceous infectious particles cause scrapie. Science. — The radical, Nobel-winning prion idea — a self-templating misfolded shape.

Hardy, J.A., & Higgins, G.A. (1992). Alzheimer’s disease: the amyloid cascade hypothesis. Science. — The hypothesis that organized — and arguably distorted — three decades of Alzheimer’s research.

van Dyck, C.H., et al. (2023). Lecanemab in early Alzheimer’s disease. New England Journal of Medicine. — and Sims, J.R., et al. (2023). Donanemab in early symptomatic Alzheimer’s disease (TRAILBLAZER-ALZ 2). JAMA. — The first anti-amyloid drugs to slow decline — a modest, risky, genuinely real effect that both partly vindicates and partly indicts the amyloid hypothesis.

Jumper, J., et al. (2021). Highly accurate protein structure prediction with AlphaFold. Nature. — Varadi, M., et al. (2022). AlphaFold Protein Structure Database… Nucleic Acids Research. — and Abramson, J., et al. (2024). Accurate structure prediction of biomolecular interactions with AlphaFold3. Nature. — The solving of protein-structure prediction (Hassabis and Jumper, 2024 Nobel Prize in Chemistry), the database, and the extension toward interactions — read with the chapter’s footnote about what it does not predict.

Rubinsztein, D.C., Mariño, G., & Kroemer, G. (2011). Autophagy and aging. Cell. — Why the cleanup crews falling behind is central to aging.

Chapter 7 — Reprogramming

Gurdon, J.B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology. — The nuclear-transfer experiments showing an adult cell retains all the instructions for a whole organism.

Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. — The four-factor reset (2012 Nobel Prize, shared with Gurdon): proof that cell identity is reversible.

Lapasset, L., et al. (2011). Rejuvenating senescent and centenarian human cells by reprogramming through pluripotency. Genes & Development. — Reprogramming resets the markers of cellular age toward zero.

Ocampo, A., et al. (2016). In vivo amelioration of age-associated hallmarks by partial reprogramming. Cell. — The proof of concept that partial, cyclic reprogramming can rejuvenate a living mammal without teratomas.

Lu, Y., et al. (2020). Reprogramming to recover youthful epigenetic information and restore vision. Nature. — Partial reprogramming (OSK) restoring vision in mice — the strongest demonstration of restored function, and the science behind the first human trial.

Conboy, I.M., et al. (2005). Rejuvenation of aged progenitor cells by exposure to a young systemic environment. Nature. — and Mehdipour, M., et al. (2020). Rejuvenation of three germ layers’ tissues by exchanging old blood plasma with saline-albumin. Aging. — Heterochronic parabiosis, and the later evidence that diluting old blood matters more than adding young.

Hou, P., et al. (2013). Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds. Science. — and Guan, J., et al. (2022). Chemical reprogramming of human somatic cells to pluripotent stem cells. Nature. — Reprogramming with drugs instead of genes — the route most amenable to AI-driven discovery.

(The first human trial of partial epigenetic reprogramming — a Phase 1 study for an eye disease — was cleared by the U.S. FDA in early 2026; see the sponsor’s announcements and the public trial registry for current status.)

The Reckoning

Olshansky, S.J., et al. (2024). Implausibility of radical life extension in humans in the twenty-first century. Nature Aging. — The core of the chapter’s answer (and listed under the Introduction above).

Goldman, D.P., et al. (2013). Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Affairs. — The geroscience case: why targeting aging itself beats fighting one disease at a time, and why curing any single disease buys surprisingly little.

López-Otín, C., et al. (2013; 2023). The hallmarks of aging / Hallmarks of aging: An expanding universe. Cell. — The synthesis to return to.

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A closing note. This list is a starting point, not a boundary. Every paper here is embedded in a web of others — the studies it built on, the ones that challenged it, the ones that came after. Follow those threads. The most important thing these references can teach you is not any single result but the texture of how the work is actually done: provisional, argued-over, self-correcting, and far more honest with itself than the headlines that summarize it. That texture is the real subject of this book.

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