Longevity & Aging
partial reprogramming (OSK) improves youthful cellular function
In plain terms: Can resetting cells make tissues young again?
Leans support(Animal or laboratory evidence) Longevity & Aging 🐭 Non-human evidence🔬 Includes disconfirming
Part of: 🩺 partial reprogramming (osk)
RefutedContestedStrong support
consensus score 0.90
Yes, but only shown in animals so far, with zero human data and real tumor-risk concerns.
📅 Last reviewed: 2026-07-14 ⓘ
Evidence ladder
How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."
Top evidence so far: Animal studies (Animal)
MechanismIn-vitroAnimalObservationalRCTMeta-analysis
How the studies fall
12 support 1 contradict 0 tested null 0 mixed · 13 sources, 11 independent groups
What the evidence shows
Mouse landmark, independently replicated in physiologically aged wild-type mice (Browder 2022). Mouse-only; teratoma / identity-loss risk if expression is unchecked. Zero human data.
The evidence (16)
| Source | Grade | Stance | Quality | Finding |
|---|---|---|---|---|
| Paine PT, Nguyen A, Ocampo A 2024 · Aging Cell | observational | supports | moderate | Review of partial reprogramming as rejuvenation tech: striking mouse benefits but cell-identity-loss/tumor risks, no human data |
| Browder KC, Reddy P, Yamamoto M, Haghani A, Guillen IG, Sahu S, Wang C, Luque Y, Prieto J, Shi L, Shojima K, Hishida T, Lai Z, Li Q, Choudhury FK, Wong WR, Liang Y, Sangaraju D, Sandoval W, Esteban CR, Delicado EN, Garcia PG, Pawlak M, Vander Heiden JA, Horvath S, Jasper H, Izpisua Belmonte JC 2022 · Nat Aging | animal | supports | moderate | Browder 2022 NatAging partial reprog rejuvenates kidney/skin physiologically-aged WT mice. ANIMAL-ONLY |
| Yang JH, Petty CA, Dixon-McDougall T, Lopez MV, Tyshkovskiy A, Maybury-Lewis S, Tian X, Ibrahim N, Chen Z, Griffin PT, Arnold M, Li J, Martinez OA, Behn A, Rogers-Hammond R, Angeli S, Gladyshev VN, Sinclair DA 2023 · Aging (Albany) | in-vitro | supports | low | Chemical cocktails mimic OSK to reverse cellular-aging markers and restore youthful transcriptome in human cells; non-genetic route |
| Macip CC, Hasan R, Hoznek V, Kim J, Lu YR, Metzger LE, Sethna S, Davidsohn N 2024 · Cellular Reprogramming | animal | supports | low | Gene-therapy OSK partial reprogramming extends lifespan and reverses age-related changes in aged wild-type mice; replication, mouse-only |
| Jones RG, Dimet-Wiley A, Haghani A, da Silva FM, Brightwell CR, Lim S, Khadgi S, Wen Y, Dungan CM, Brooke RT, Greene NP, Peterson CA, McCarthy JJ, Horvath S, Watowich SJ, Fry CS, Murach KA 2023 · J Physiol | animal | supports | moderate | Muscle-specific in-vivo OKSM reprogramming shares a molecular signature with exercise adaptation in aged mouse skeletal muscle |
| Teefy BB, Benayoun BA 2023 · Cell Metabolism | animal | mixed | high | Commentary, not a study: 'A recent report by Yang et al. in Cell demonstrates that faithful DNA double-strand breaks and repair cycles phenocopy many aspects of aging in mice. Whether this progeroid phenotype is caused by a loss of epigenetic information remains to be conclusively determined.' Review — zero weight; the data belong to Yang 2023. |
| Ocampo A, Reddy P, Martinez-Redondo P, Platero-Luengo A, Hatanaka F, Hishida T, Li M, Lam D, Kurita M, Beyret E, Araoka T, Vazquez-Ferrer E, Donoso D, Roman JL, Xu J, Rodriguez Esteban C, Nuñez G, Nuñez Delicado E, Campistol JM, Guillen I, Guillen P, Izpisua Belmonte JC 2016 · Cell | animal | supports | moderate | Ocampo 2016 Cell OSKM ameliorates aging+extends lifespan progeroid mice. ANIMAL/MECHANISM-ONLY |
| Doeser MC, Schöler HR, Wu G 2018 · Stem Cells | animal | supports | moderate | Transient in-vivo partial reprogramming reduces fibrosis/scar formation while avoiding teratoma; functional benefit in mice |
| de Lázaro I, Yilmazer A, Nam Y, Qubisi S, Razak FMA, Degens H, Cossu G, Kostarelos K 2019 · Mol Ther | animal | supports | moderate | Non-viral transient OKSM in mouse skeletal muscle enhances regeneration tumor-free; transient expression avoids tumorigenesis |
| Horvath S, Lacunza E, Mallat MC, Portiansky EL, Gallardo MD, Brooke RT, Chiavellini P, Pasquini DC, Girard M, Lehmann M, Yan Q, Lu AT, Haghani A, Gordevicius J, Abba M, Goya RG 2025 · Geroscience | animal | supports | moderate | OSKM gene therapy in 25-month-old rats (39 days, hippocampus): improved spatial memory and partially reversed age-related hippocampal DNA-methylation aging — new in-vivo evidence partial reprogramming restores a youthful FUNCTION (cognition). Animal. |
| Wang P, Wang R, Huo Y, Peng Y, Fu C, Hu Y, Ren Z, Mulat Y, Zhang H, Jiang D, Lin H 2025 · Adv Sci (Weinh) | animal | supports | moderate | Pulsed partial reprogramming in senescent Schwann cells reset stress-granule/proteostasis homeostasis and enhanced peripheral nerve function — additional in-vivo support that partial reprogramming restores youthful cell function (animal). |
| Schoenfeldt L, Paine PT, Picó S, Kamaludeen M NH, Phelps GB, Mrabti C, Desdín-Micó G, Del Carmen Maza M, Perez K, Ocampo A 2025 · EMBO Mol Med | in-vitro | supports | moderate | Chemical reprogramming ameliorates aging hallmarks and extends lifespan; independent support for reprogramming-based rejuvenation |
| Hu D, Borgne EL, Meinl R 2023 · Cellular Reprogramming | animal | supports | low | Commentary, not a study: 'A recent study in Aging Cell showed that transcriptional activation of endogenous Oct4 using the CRISPR/dCas9 activator system is sufficient for cellular rejuvenation and extending the lifespan of a progeria mouse model.' Authors at Retro Biosciences. Review — zero weight; the underlying Aging Cell paper is the evidence. |
| Lu Y, Brommer B, Tian X, Krishnan A, Meer M, Wang C, Vera DL, Zeng Q, Yu D, Bonkowski MS, Yang JH, Zhou S, Hoffmann EM, Karg MM, Schultz MB, Kane AE, Davidsohn N, Korobkina E, Chwalek K, Rajman LA, Church GM, Hochedlinger K, Gladyshev VN, Horvath S, Levine ME, Gregory-Ksander MS, Ksander BR, He Z, Sinclair DA 2020 · Nature | animal | supports | moderate | OSK (Myc omitted) reprogramming improves tissue function in mice; demonstrates reversibility but mouse-only |
| Chondronasiou D, Gill D, Mosteiro L, Urdinguio RG, Berenguer-Llergo A, Aguilera M, Durand S, Aprahamian F, Nirmalathasan N, Abad M, Martin-Herranz DE, Stephan-Otto Attolini C, Prats N, Kroemer G, Fraga MF, Reik W, Serrano M 2022 · Aging Cell | animal | supports | moderate | Single transient OSKM cycle drives multi-omic rejuvenation of naturally aged mouse tissues without changing cell identity |
| Griscelli F, Féraud O, Oudrhiri N, Gobbo E, Casal I, Chomel JC, Biéche I, Duvillard P, Opolon P, Turhan AG, Bennaceur-Griscelli A 2012 · Am J Pathol | in-vitro | contradicts | moderate | Partially reprogrammed human iPSCs form malignant germ-cell-like tumors on differentiation; flags tumorigenic safety risk |
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