About This Project

Muscle loss occurs during spaceflight, aging, and prolonged inactivity, but these conditions may be driven by different gene-regulatory signals. I analyzed publicly available mouse muscle datasets to identify transcription factors, proteins that control gene activity, shared across these forms of atrophy or unique to each one. The results reveal both common stress-related regulators and condition-specific patterns that may help prioritize future muscle-wasting research.

Ask the Scientists

What is the context of this research?

Muscle atrophy, the loss of muscle mass and strength, occurs during aging, prolonged inactivity, and spaceflight. Prior studies comparing these conditions gene-by-gene found only modest overlap, suggesting shared regulation may be better detected at the transcription-factor (TF) level, which are the proteins that switch genes on or off.

I hypothesized that comparing TF activity, not just genes, across spaceflight, aging, and disuse would reveal a shared "pan-atrophy" regulatory core obscured at the gene level. Using NASA OSD-576 (spaceflight), GSE145480 (aging), and GSE273092 (disuse), I applied decoupleR to infer TF activity, building on foundational work showing FoxO factors drive atrogin-1/MuRF1-mediated atrophy.

My study is now published open access in PLOS ONE: Transcription factor activity divergence across muscle atrophy conditions: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359659

What is the significance of this project?

Most prior comparisons of muscle-wasting conditions examined individual genes, where overlap between spaceflight, aging, and disuse appears modest. This study instead compares TF activity, the upstream regulators of those genes, to test whether a shared regulatory core becomes visible where gene-level analysis falls short.

My published study found that 47 of 732 scored TFs (6.4%) are active across all three conditions, centered on stress and glucocorticoid signaling, while most TFs are condition-specific. This generates hypotheses for future experimental validation; it does not establish causality, and follow-up work (e.g., knockdown studies) would be needed to confirm mechanisms.

Because all datasets are mouse-derived, findings represent candidate mechanisms rather than confirmed human biology; further work is needed to test conservation in humans.

What are the goals of the project?

This project analyzed transcription-factor activity across three public mouse datasets representing spaceflight, aging, and disuse-induced muscle atrophy, to identify TFs shared across all three conditions versus those specific to a single stressor.

The research is complete and has been published open access in PLOS ONE on October 1, 2026. PLOS has invoiced the $2,477 article processing charge, which remains unpaid. Funds from this campaign will go directly toward that invoice so the study stays freely available to researchers, students, and the public.