In a breakthrough for regenerative medicine, researchers at The Chinese University of Hong Kong have repurposed Maraviroc—a well-known antiretroviral drug used to treat HIV—to reverse sarcopenia, the debilitating muscle loss associated with aging. By constructing the world’s first comprehensive “atlas” of senescent cells within human skeletal muscle, the team identified a specific chemical signal that drives muscle deterioration: the CCL5-CCR5 axis.
As we age, “zombie” cells (senescent cells) accumulate in our tissues. Instead of dying, they spew out a toxic cocktail of inflammatory factors known as the SASP (Senescence-Associated Secretory Phenotype). This study reveals that in muscle tissue, this toxic chatter is mediated largely by the CCR5 receptor. When the researchers blocked this receptor in aged mice using Maraviroc, the results were striking: the animals didn’t just stop losing muscle; they regained grip strength, running endurance, and muscle mass. Essentially, the drug silenced the inflammatory noise, allowing muscle stem cells to “wake up” and repair tissue.
This finding suggests that sarcopenia is not an inevitable slide into frailty but an active, reversible process driven by immune signaling. Because Maraviroc is already FDA-approved with a known safety profile, this research bypasses the decade-long safety testing required for novel compounds, offering a potential fast-track to clinical trials for frailty.
Open Access Research Paper: “Multiomics and cellular senescence profiling of aging human skeletal muscle uncovers Maraviroc as a senotherapeutic approach for sarcopenia”.
- Institution: The Chinese University of Hong Kong (CUHK), Hong Kong SAR, China.
- Journal: Nature Communications (Published online July 5, 2025).
- Impact Evaluation: The impact score of this journal is ~15.7 (2024/2025 JIF), evaluated against a typical high-end range of 0–60+ for top general science, therefore this is a High impact journal.
Benefits over 3 months of treatment
Metric / Improvement
Muscle Mass, +28%
Fiber Diameter, +15%
Grip Strength, +16%
Endurance, +20%
Part 2: The Biohacker Analysis
Study Design Specifications
- Type: In vivo (murine intervention) and In vitro/Ex vivo (Human Single-Nucleus Multiomics Atlas).
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Subjects:
- Animal: Aged C57BL/6 mice (18 months old, approx. 56 human years).
- Human: Skeletal muscle biopsies from young (19-27y) vs. aged (60-77y) donors for atlas generation.
- N-number: Mice n=8 per group; Human donors n=10.
- Lifespan Data: Not Reported. The study focused exclusively on healthspan metrics (sarcopenia reversal) over a 3-month treatment window. No median or maximum lifespan curves were generated.
Mechanistic Deep Dive
The study identifies the CCL5-CCR5 axis as a critical driver of the senescence-associated secretory phenotype (SASP) in skeletal muscle.
- Pathway: Senescent cells in aged muscle secrete high levels of CCL5, which binds to CCR5 receptors on neighboring cells (paracrine) and the senescent cells themselves (autocrine).
- Downstream Effect: This binding activates NF-κB and MAPK pathways, perpetuating inflammation and locking muscle stem cells (MuSCs) in a dysfunctional state.
- Intervention: Maraviroc (a CCR5 antagonist) breaks this feedback loop. Unlike senolytics (e.g., Dasatinib + Quercetin) which kill senescent cells, Maraviroc acts as a senomorphic—it suppresses the toxic SASP phenotype without necessarily killing the cell, effectively “muting” the zombie cells.
- Organ Priority: Skeletal Muscle (specifically improving MuSC regenerative capacity).
Novelty
- First Human Senescence Atlas: Creates a high-resolution map of exactly which cell types become senescent in human muscle (identifying heterogeneity previously missed).
- Drug Repurposing: Validates an FDA-approved HIV entry inhibitor as a potent anti-sarcopenia agent, shifting the focus from “killing” senescent cells to interfering with their intercellular signaling.
Critical Limitations
- Route of Administration: The mice received intraperitoneal (i.p.) injections. Maraviroc has variable oral bioavailability in humans (~23-33%), so translational efficacy via oral dosing remains to be confirmed for this specific indication.
- Short Duration: The treatment lasted only 3 months. Long-term effects of chronic CCR5 inhibition in non-HIV populations (e.g., immune surveillance risks) are not fully characterized in the context of aging.
- No Lifespan Data: We do not know if this healthspan improvement translates to extended life.
- Missing Data: The study did not report effects on other organs (liver, kidney) where CCR5 might play a different role in aging.
Part 3: Actionable Intelligence
The Translational Protocol
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Human Equivalent Dose (HED):
- Animal Dose: 10 mg/kg (administered every 2 days).
- Math: 10 mg/kg×(3/37)≈0.81 mg/kg.
- Human Result: For a 70 kg human, this is ~57 mg (every 2 days) or roughly 30 mg/day.
- Note: The standard clinical dose for HIV is 300 mg BID (600 mg/day). The longevity/sarcopenia effective dose appears to be ~1/20th of the antiviral dose, suggesting a wide therapeutic window.
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Pharmacokinetics (PK/PD):
- Bioavailability: ~23–33% (Oral). Increases significantly with high-fat meals (reduced absorption) or strong CYP3A inhibitors (increased exposure).
- Half-life: ~14–18 hours. Daily dosing is sufficient to maintain blockade.
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Safety & Toxicity Check:
- Safety Profile: Generally well-tolerated.
- NOAEL (Mice): 200 mg/kg/day (significantly higher than the 10 mg/kg efficacy dose).
- Black Box/Warnings: Hepatotoxicity (liver toxicity) has been reported. Severe hypersensitivity reactions (SJS/TEN) are rare but possible.
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Interactions: Major CYP3A4 substrate.
- Contraindication: Do not mix with St. John’s Wort (inducer).
- Caution: Interaction with Rapamycin (Sirolimus) is highly probable as both compete for/are metabolized by CYP3A4.
Related reading: Maraviroc Fights Middle-Aged Memory Loss (And Muscle Aging)
