A 2023 rodent study investigated Nrf2’s capacity to reverse cell senescence:

“Poly-D,L-lactic acid (PDLLA) filler corrects soft tissue volume loss by increasing collagen synthesis in the dermis. Adipose-derived stem cells (ASCs) are known to attenuate the decrease in fibroblast collagen synthesis that occurs during aging.

Conclusions:

1. PDLLA increased macrophage NRF2 expression, resulting in increased M2 polarization and IL-10 expression in senescent macrophages and aged skin.
2. Increased IL-10 expression by macrophages led to reduced ASC senescence, and increased ASC proliferation and paracrine secretion of TGF-β and FGF2.
3. Increased TGF-β and FGF2 levels in turn led to increased fibroblast proliferation and synthesis of collagen and elastin fibers.
4. PDLLA-modulated macrophage not only directly stimulated fibroblast activity, promoting proliferation and collagen synthesis, but also reduced expression of NF-kB and MMP2/3/9.

These effects ultimately led to skin rejuvenation in aged skin.”

https://www.mdpi.com/2076-3921/12/6/1204 “Poly-D,L-Lactic Acid Filler Increases Extracellular Matrix by Modulating Macrophages and Adipose-Derived Stem Cells in Aged Animal Skin”

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This study’s Nrf2 activator was persistent. Per Part 1’s findings, that probably won’t work out well long-term, as constant Nrf2 activation may cause cell senescence. It would still be worthwhile for other researchers to replicate this study’s rejuvenation effects using other Nrf2 activators with different activation periods and additional senescence measurements.

It was this study’s H₂O₂ and unmeasured aging environments that caused cell senescence. Other studies could follow principles of An environmental signaling paradigm of aging and rejuvenate by changing subjects’ aging environments since:

“It is clear that the increasing number of senescent cells depends on the post-adult developmental stage rather than chronological age. The coincidence that these processes result in particular forms of impairment in old age does not seem to be random as it is present in all mammals, and may be causative of many aspects of aging.”

Maybe similar to how Environmental signaling rescues aging muscle stem cells reversed aged muscle stem cell gene expression?