From "Stopping" Aging to "Reversing" It? Four Rejuvenation Factors Identified from 30 Candidates

1) Where Does "Resilience Aging" Occur?

As we age, cuts heal more slowly, colds linger longer, and recovery from surgery takes more time. This decline in "resilience" is one of the most tangible changes in aging that directly impacts daily life.

In January 2026, research from the University of California, San Francisco (UCSF) focused on fibroblasts as the cells underlying this decline in resilience. They demonstrated the potential to revert aged cells to a younger state by manipulating "transcription factors," proteins that control the on/off state of genes.

2) The Main Player: Fibroblasts Supporting the "Scaffold" and Repair Process of Tissues

Fibroblasts create the "scaffold (extracellular matrix)" that fills the spaces between cells in organs and skin, maintaining tissue shape and facilitating repair when damage occurs. However, as aging slows the movement and function of fibroblasts, both scaffold maintenance and repair processes become delayed.

This is a key point: while discussions on aging often drift towards "lifespan" or "appearance," the focus here is on the more practical "self-repair ability." The scope of treatment could be more about "fixing the difficulty in healing" rather than chasing the dream of anti-aging.

3) The Core of the Research: A Comprehensive Approach to Target Aging

Aging research is challenging due to the multitude of potential causes. Gene expression, mitochondria, inflammation, protein quality control, and epigenetics (acquired gene regulation) are all intertwined, making it difficult to distinguish cause from effect.

In response, the research team

• first captured the changes in gene expression occurring in aged fibroblasts

• identified potential "transcription factors" driving these changes through computational analysis

• and used Perturb-seq with CRISPR to manipulate each transcription factor and compare effects

forming a "discovery→verification" flow.

4) "Among 30 Factors, Some Work Alone": E2F3/EZH2/STAT3/ZFX

Upon examining 30 transcription factor candidates, factors that could reverse aging characteristics even when manipulated alone were identified. Specifically, increasing E2F3 or EZH2 and suppressing STAT3 or ZFX were the four directions noted.

These individual manipulations reportedly led to improvements in cell proliferation, maintenance of protein health (proteostasis), and mitochondrial activity, reducing cellular aging (senescence).

When we hear "rejuvenation," we often imagine large-scale genetic alterations, but this is a novel point. It showed the possibility that aging characteristics could collectively shift even with a single control point.

5) A Further Step: Improvement of "Elderly Mouse Liver" with EZH2

The research was not limited to cell experiments but was also verified in mice. Increasing EZH2 in elderly (20-month-old) mice improved liver fibrosis, reduced fat accumulation in the liver, and enhanced glucose tolerance.

What emerges here is a form of rejuvenation aimed at the "practical benefits" of metabolism and organ function, rather than "appearance." Fatty liver, fibrosis, and glucose metabolism disorders tend to increase with age and are directly linked to healthy lifespan.

6) However, the Biggest Issue is Safety: Transcription Factors Are Too Powerful

Transcription factors are "master levers" at the upstream of gene networks. If effective, they can have a significant impact, but if too effective, they can be dangerous. Particularly, "increased proliferation" and "reduced senescent cells" can be closely related to tumorigenesis (cancer) depending on the context.

The research highlights that aging reversal was observed "without inducing dedifferentiation or tumorigenic programs," but this is under experimental conditions. Clinical verification will require separate phases to address long-term administration, systemic effects, off-target tissue impacts, and delivery methods (gene introduction or drugs).

Moreover, since the research is connected to corporate activities, transparency, including conflicts of interest and patents, becomes crucial. Rejuvenation research is an area where expectations tend to run high, making discussions on reproducibility and safety indispensable.

7) Translating into "Treatment": Aiming for "Single Targets" Instead of CRISPR

This achievement is positioned in the context of drug discovery and treatment development, as well as basic research. If aging indicators can be shifted with a single target, the design of drugs becomes simpler. If it can be translated into a method that can be adjusted through administration (e.g., nucleic acid medicine) rather than permanently rewriting genes, it will be easier to control from a safety perspective.

However, questions remain about which cells to target, to what extent, and for how long. How to monitor side effects? Treating aging as a "target for treatment" requires not only scientific but also medical implementation design.

8) Reactions on Social Media: A Topic Where "Expectations and Caution Grow Simultaneously"

This news spreads easily on social media. Words like "rejuvenation," "resilience," and "reversing aging" are powerful, yet prone to misunderstanding.

Common reactions include the following patterns:

• Expectations (Medical): "If healing delays in the elderly improve, the landscape of post-surgery recovery and chronic diseases will change."

• Expectations (Metabolic): "If fatty liver, fibrosis, and glucose metabolism improve, it directly impacts healthy lifespan."

• Caution (Translatability): "Mice and humans are different. Will it work beyond the liver?"

• Concerns (Safety): "Increased proliferation = cancer risk? Are transcription factors too strong?"

• Practical (Implementation): "How to deliver it to targeted cells? How long will it last?"

The important point is that this achievement does not mean "a drug that makes people rejuvenate immediately" has been developed, but rather it demonstrates the stage where "the aged state can be shifted from a single control point." The more excitement there is on social media, the more careful we should be in drawing lines.

9) Conclusion: The Trend of Treating Aging as a "Design Problem" Accelerates

This research has shifted the perception of aging from "too complex to handle" to "something that might have targetable control points."

By capturing fibroblast aging data, identifying transcription factor candidates, verifying the effects of single factors through single-cell analysis, and demonstrating improved function in elderly mouse livers with EZH2, rejuvenation research has moved closer to an engineering question of "which control points to manipulate" rather than just a "dream."

However, transcription factor manipulation is powerful, and clinical application requires safety and transparency. Given the tendency for expectations to run high, the real challenge lies in the accumulation of further verification from this point onward.

Reference URLs (Copying here will ensure links are retained)

PNAS Paper (PubMed Abstract)
https://pubmed.ncbi.nlm.nih.gov/41512022/

UCSF News Release (EurekAlert!)
https://www.eurekalert.org/news-releases/1112231

Junevity Announcement (Business Wire)
https://www.businesswire.com/news/home/20260112739359/en/Junevity-Announces-First-Peer-Reviewed-Research-Showing-Single-Target-Repression-Can-Reprogram-Cellular-Aging

(SNS Example) Reddit (r/longevity Thread)
https://www.reddit.com/r/longevity/comments/1i4a608/singlefactor_transcriptional_reprogramming/