Longevity Papers 2025-06-13: A single factor for safer cellular rejuvenation
In this episode of Longevity Papers, we critically analyze a groundbreaking new paper for biotech researchers and longevity enthusiasts: A single factor for safer cellular rejuvenation by Camillo et al. from Shift Bioscience, posted to bioRxiv on June 6, 2025 (https://doi.org/10.1101/2025.06.05.657370). The paper introduces a single, anonymous gene, SB000, discovered through a novel rejuvenation-first screening platform. The authors claim SB000 rivals the rejuvenation potency of the famous Yamanaka factors (OSKM) without inducing the dangerous pluripotency that has hindered their therapeutic use. We delve into the multi-omic evidence, including the dramatic reversal of epigenetic clocks in both fibroblasts (Figure 2) and keratinocytes (Figure 4) - by as much as 13.6 years in skin cells. We also examine the crucial safety data from Figure 3, which shows SB000 preserves cellular identity and function, like collagen secretion, and, unlike OSK, fails to form pluripotent colonies in long-term culture. While the findings are exciting, we maintain a healthy skepticism, discussing the major limitations: this is an un-reviewed preprint, the identity of SB000 is a trade secret, the discovery relies on a proprietary black box clock, and all experiments are conducted in vitro, a far cry from a living organism. Finally, we propose the essential follow-up studies needed to validate these claims, from dissecting the genes mechanism of action to the critical in vivo proof-of-concept experiments in aged mice to test for true healthspan improvements and, most importantly, long-term safety.