# Oliver Hahn

> In middle school I read about DNA replication failures and got hooked on aging. Now I lead brain aging at Calico. Put young immune cells into an old brain and it ages them fast. I build discovery engines to find what drives brain aging.

Principal Investigator for Brain Aging, Calico Life Sciences.

## Links

- [X](https://x.com/Oliver__Hahn)
- [LinkedIn](https://www.linkedin.com/in/oliver-hahn-ph-d-2363b3141/)
- [Google Scholar](https://scholar.google.com/citations?user=vpa2PmUAAAAJ)
- [GitHub](https://github.com/olihahn)

## Papers

Also as [JSON](papers.json) and [BibTeX](papers.bib).

- [Heterochronic myeloid cell replacement reveals the local brain environment as key driver of microglia aging](https://www.biorxiv.org/content/10.1101/2025.09.02.673859v1) bioRxiv (preprint), 2025. Young replacement microglia, the brain's immune cells, aged fast in old brains. Old ones looked young in young brains.
- [Atlas of the aging mouse brain reveals white matter as vulnerable foci](https://www.cell.com/cell/fulltext/S0092-8674(23)00805-X) Cell, 2023. We profiled 15 mouse brain regions across 7 ages. Glial aging runs faster in white matter than cortex.
- [CoolMPS for robust sequencing of single-nuclear RNAs captured by droplet-based method](https://doi.org/10.1093/nar/gkaa1127) Nucleic Acids Research, 2020. CoolMPS sequencing reproduced standard Illumina results on single-nucleus RNA from young and old mouse hippocampus.
- [Ageing hallmarks exhibit organ-specific temporal signatures](https://www.nature.com/articles/s41586-020-2499-y) Nature, 2020. Organs hit the same aging hallmarks on different schedules. Immune activation shows first in white fat.
- [A nutritional memory effect counteracts the benefits of dietary restriction in old mice](https://www.nature.com/articles/s42255-019-0121-0) Nature Metabolism, 2019. In 800 mice, stopping dietary restriction at 24 months raised mortality fast. Starting it late helped only weakly.
- [Hepatic gene body hypermethylation is a shared epigenetic signature of murine longevity](https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007766) PLOS Genetics, 2018. Dietary restriction, rapamycin and dwarf genetics each add methylation inside gene bodies in mouse liver.
- [Dietary restriction protects from age-associated DNA methylation and induces epigenetic reprogramming of lipid metabolism](https://link.springer.com/article/10.1186/s13059-017-1187-1) Genome Biology, 2017. Dietary restriction delayed age-related epigenetic changes in mouse liver and added methylation at lipid genes.
- [A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase](https://www.nature.com/articles/s41467-025-59860-6) Nature Communications, 2025. A microRNA atlas of 15 mouse brain regions. miR-155-5p rises with age in both sexes, driven by microglia.
- [Myeloid cell replacement is neuroprotective in chronic experimental autoimmune encephalomyelitis](https://www.nature.com/articles/s41593-024-01609-3) Nature Neuroscience, 2024. Replacing immune cells by transplant improved neurological deficits in a mouse model of multiple sclerosis.
- [Characterizing expression changes in noncoding RNAs during aging and heterochronic parabiosis across mouse tissues](https://www.nature.com/articles/s41587-023-01751-6) Nature Biotechnology, 2023. A noncoding RNA map of 16 organs. miR-29c-3p tracks aging and returns to young levels in liver with young blood.
- [Ageing-associated changes in transcriptional elongation influence longevity](https://www.nature.com/articles/s41586-023-05922-y) Nature, 2023. RNA polymerase speeds up with age in five species. Dietary restriction reverses most of this, and slowing polymerase extends lifespan.
- [Platelet factors are induced by longevity factor klotho and enhance cognition in young and aging mice](https://www.nature.com/articles/s43587-023-00468-0) Nature Aging, 2023. Klotho raises platelet factors in blood. One of them, PF4, improves cognition in young and old mice.
- [Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17](https://www.nature.com/articles/s41586-022-04722-0) Nature, 2022. Young cerebrospinal fluid improved memory in old mice. Fgf17 alone did too.
- [Exercise plasma boosts memory and dampens brain inflammation via clusterin](https://www.nature.com/articles/s41586-021-04183-x) Nature, 2021. Plasma from running mice reduced brain inflammation in sedentary mice, through proteins including clusterin.
- [Dysregulation of brain and choroid plexus cell types in severe COVID-19](https://www.nature.com/articles/s41586-021-03710-0) Nature, 2021. Brains from COVID-19 patients showed no molecular trace of virus but broad changes in barrier cells and microglia.
- [Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain](https://www.nature.com/articles/s41593-019-0566-1) Nature Neuroscience, 2020. Microglia fill with lipid droplets as brains age. These cells clear debris poorly and drive inflammation.
- [A single-cell transcriptomic atlas characterizes ageing tissues in the mouse](https://www.nature.com/articles/s41586-020-2496-1) Nature, 2020. A single-cell atlas of aging across 23 mouse tissues and organs.
- [The Sense of Smell Impacts Metabolic Health and Obesity](https://www.cell.com/cell-metabolism/fulltext/S1550-4131(17)30357-1) Cell Metabolism, 2017. Mice that lost smell neurons resisted diet-induced obesity. Losing smell after obesity reduced fat mass.
- [Inferring causal molecular networks: empirical assessment through a community-based effort](https://www.nature.com/articles/nmeth.3773) Nature Methods, 2016. A community challenge scored over 2,000 networks for causal links in cancer cell signaling.

## Projects

- [Ember](https://github.com/olihahn/ember-app) A cigar journal for Android. Its home screen is a painted terrace you can lean into.
- [Sentinel](https://github.com/Vanthys/tcr-agent) Agent proposing antigen targets for unknown T cell receptors. Second of 70 teams and People's Choice, Bio x AI Hackathon.
- [Brain aging atlas browser](https://twc-stanford.shinyapps.io/spatiotemporal_brain_map/) Explore gene expression across 15 mouse brain regions and 7 ages. Code and data are public.

## Writing

- [What changes in normal human brain aging](https://www.linkedin.com/feed/update/urn:li:activity:7510644745455669248/) 284 human brains echo our mouse atlas: microglia and other glia change most with age, especially in white matter.
- [Biology has to be able to answer back](https://www.linkedin.com/feed/update/urn:li:activity:7485271114232037376/) AI in biology needs causal tests in living systems. We read them, write changes into them, and reason over results.
- [What my Paperpile library says about me](https://www.linkedin.com/feed/update/urn:li:activity:7454267222983827456/) I pointed Claude Code at my 2,052 saved papers. It found my forgotten PhD project on cardiolipin.
- [First unlock from vibe science: public datasets](https://www.linkedin.com/feed/update/urn:li:activity:7451925605182509056/) AI agents make public data usable fast. I combined 107,219 perturbations from 5 Perturb-seq sources into one collection.
- [Computational biology is the quiet AI win](https://www.linkedin.com/feed/update/urn:li:activity:7450494127038758912/) Computational biology is where AI is doing the most for science right now, more than hypothesis generators or lab robots.
- [DNA methylation dynamics in murine ageing and longevity (PhD thesis abstract, University of Cologne)](https://kups.ub.uni-koeln.de/8577/) My PhD on how DNA methylation changes with aging, dietary restriction and longevity in mice.