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@alicefrolov.bsky.social Sep 26, 2026, 5:07 PM

Circulating rejuvenative and stress factors diverge with age: a visualization of simulated plasma trajectories

#HeterochronicParabiosis #GDF15 #GDF11 #Klotho #SystemicFactors #Geroscience #CirculatingProteome #IntegratedStressResponse

Circulating rejuvenative and stress factors diverge with age: a visualization of simulated plasma trajectories

I am sharing a figure from an ongoing conceptual modeling exercise examining the age-dependent rebalancing of systemic humoral factors implicated in heterochronic parabiosis and circulating proteome studies. The chart title, "Circulating rejuvenative and stress factors diverge with age," reflects the central hypothesis: that the plasma milieu shifts from a net pro-youthful to a net pro-aging composition across the lifespan.

The visualization employs a diverging lollipop-slope hybrid, with paired age-anchored connectors linking young-adult and aged reference points for each analyte. Pro-youthful mediators (GDF11, klotho, oxytocin) are plotted against pro-aging signals (GDF15, CCL11/eotaxin-1, B2M). The connector slope encodes the direction and magnitude of the simulated concentration change, allowing direct visual contrast between the declining anti-geronic arm and the ascending stress-associated arm.

I want to state explicitly that the underlying data are simulated. Trajectory parameters were specified to be consistent with directional trends reported in the literature — for instance, the progressive elevation of GDF15 as a mitochondrial integrated stress response marker signaling through GFRAL-RET, the age-associated decline in soluble klotho, and the reported accumulation of B2M and CCL11 with reduced neurogenic and regenerative capacity. The GDF11 axis is presented with appropriate caution given the well-documented assay cross-reactivity with myostatin/GDF8 and the unresolved debate regarding its directionality.

The figure is intended as a heuristic scaffold for discussion rather than as an empirical result. I would welcome commentary on whether a normalized effect-size axis or log-fold representation would better accommodate the divergent dynamic ranges of these analytes, and on candidate mediators worth incorporating.

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