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GDF15 and Related Biomarkers
Research Guide
What is GDF15 and Related Biomarkers?
GDF15 and related biomarkers refer to Growth Differentiation Factor-15 (GDF15), also known as Macrophage Inhibitory Cytokine-1 (MIC-1), and associated factors within the TGF-β superfamily that serve as indicators in physiological processes including cardiovascular disease, obesity, metabolic homeostasis, neuroprotection, and inflammation.
The field encompasses 14,685 works examining GDF15's roles in health conditions through biomarker applications. GDF15, a member of the TGF-β superfamily, influences skeletal muscle mass regulation as shown in mice models. Related biomarkers contribute to predictions of cardiovascular events and assessments in heart failure.
Topic Hierarchy
Research Sub-Topics
GDF15 as Cardiovascular Biomarker
This sub-topic evaluates GDF15's prognostic utility in heart failure, myocardial infarction, and atherosclerosis via plasma levels and risk stratification. Researchers correlate it with NT-proBNP and imaging outcomes.
GDF15 in Obesity and Metabolism
Studies explore GDF15's anorexigenic effects via GFRAL receptor signaling, appetite suppression, and weight loss in obesity models. Researchers investigate metformin induction and gut-brain axis roles.
GDF15 in Cancer Cachexia
This area examines GDF15 overexpression by tumors driving muscle wasting, anorexia, and poor survival in cachexia. Researchers test GDF15 neutralization in preclinical models for symptom palliation.
GDF15 and Inflammation Pathways
Investigations link GDF15 to anti-inflammatory responses in sepsis, autoimmune diseases, and cytokine storms via Smad signaling. Researchers dissect stress-induced expression from macrophages and epithelia.
GDF15 as Neuroprotective Factor
Neuroprotection studies assess GDF15's roles in stroke recovery, ALS, and neurodegeneration through blood-brain barrier modulation. Researchers analyze cerebrospinal fluid levels and neuronal survival assays.
Why It Matters
GDF15 and related biomarkers enable risk prediction for major cardiovascular events and death, where multiple biomarkers including those studied added moderately to standard risk factors in assessing individual persons (Wang et al., 2006, "Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death"). In heart failure, biomarkers beyond routine measures reflect genetic, neurohormonal, inflammatory, and biochemical changes impacting cardiac myocytes and interstitium (Braunwald, 2008, "Biomarkers in Heart Failure"). GDF15 connects to cancer-associated cachexia, a condition affecting patients through muscle wasting mechanisms (Baracos et al., 2018, "Cancer-associated cachexia"). These applications support clinical decisions in cardiovascular disease and metabolic disorders, with GDF15 signaling implicated in obesity and inflammation pathways.
Reading Guide
Where to Start
"Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member" (McPherron et al., 1997) provides the foundational discovery of GDF15's role in the TGF-β superfamily and muscle regulation, serving as an accessible entry point with clear experimental evidence.
Key Papers Explained
McPherron et al. (1997) in "Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member" establishes GDF15 as a TGF-β member regulating muscle mass (3921 citations). Wang et al. (2006) in "Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death" extends this to clinical biomarker panels for cardiovascular risk (1357 citations). Braunwald (2008) in "Biomarkers in Heart Failure" builds on these by detailing heart failure biomarkers, including stress-response factors like GDF15 (1243 citations). Baracos et al. (2018) in "Cancer-associated cachexia" connects GDF15 to metabolic wasting (1537 citations), while Basisty et al. (2020) in "A proteomic atlas of senescence-associated secretomes for aging biomarker development" links it to aging secretomes (1196 citations).
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Current frontiers emphasize GDF15's integration in biomarker panels for cardiovascular and heart failure prediction, as per established works like Wang et al. (2006) and Braunwald (2008), with no recent preprints shifting focus. Research continues on its roles in cachexia and senescence without new news coverage.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Alzheimer's Disease: The Amyloid Cascade Hypothesis | 1992 | Science | 7.2K | ✕ |
| 2 | Regulation of skeletal muscle mass in mice by a new TGF-p supe... | 1997 | Nature | 3.9K | ✕ |
| 3 | Genes that act downstream of DAF-16 to influence the lifespan ... | 2003 | Nature | 2.3K | ✕ |
| 4 | Vascular pathology of homocysteinemia: implications for the pa... | 1969 | PubMed | 1.8K | ✕ |
| 5 | The KEAP1-NRF2 System: a Thiol-Based Sensor-Effector Apparatus... | 2018 | Physiological Reviews | 1.7K | ✓ |
| 6 | Cancer-associated cachexia | 2018 | Nature Reviews Disease... | 1.5K | ✕ |
| 7 | Renin-angiotensin system: biochemistry and mechanisms of action. | 1977 | Physiological Reviews | 1.4K | ✕ |
| 8 | Multiple Biomarkers for the Prediction of First Major Cardiova... | 2006 | New England Journal of... | 1.4K | ✓ |
| 9 | Biomarkers in Heart Failure | 2008 | New England Journal of... | 1.2K | ✕ |
| 10 | A proteomic atlas of senescence-associated secretomes for agin... | 2020 | PLoS Biology | 1.2K | ✓ |
Frequently Asked Questions
What is the role of GDF15 in skeletal muscle regulation?
"Regulation of skeletal muscle mass in mice by a new TGF-β superfamily member" demonstrated that a TGF-β superfamily member, identified as GDF15-related, controls skeletal muscle mass in mice (McPherron et al., 1997). This factor influences muscle growth and maintenance through signaling pathways. The work has received 3921 citations, highlighting its foundational impact.
How do multiple biomarkers predict cardiovascular events?
"Multiple Biomarkers for the Prediction of First Major Cardiovascular Events and Death" found that 10 contemporary biomarkers, including those related to GDF15 pathways, add moderately to standard risk factors for individual risk assessment (Wang et al., 2006). The study involved population cohorts tracking first major events. It has 1357 citations.
What biomarkers are used in heart failure diagnosis?
"Biomarkers in Heart Failure" reviews markers beyond routine ones, capturing interplay of genetic, neurohormonal, inflammatory, and biochemical changes in cardiac tissue (Braunwald, 2008). These include factors linked to GDF15 in stress responses. The paper has 1243 citations.
How does GDF15 relate to cancer cachexia?
"Cancer-associated cachexia" discusses cachexia mechanisms involving GDF15 as a TGF-β family member driving muscle loss in cancer patients (Baracos et al., 2018). It affects metabolic homeostasis and inflammation. The primer has 1537 citations.
What is the connection between GDF15 and aging senescence?
"A proteomic atlas of senescence-associated secretomes for aging biomarker development" identifies SASP components, including GDF15-related peptides, as drivers in age-related conditions like neurodegeneration (Basisty et al., 2020). The atlas expands on dozens of secreted proteins. It has 1196 citations.
Open Research Questions
- ? How does GDF15 signaling integrate with KEAP1-NRF2 pathways to maintain redox homeostasis in cardiovascular inflammation?
- ? What specific mechanisms link GDF15 to skeletal muscle mass loss in obesity and cachexia models?
- ? Can combinations of GDF15 and senescence-associated biomarkers improve prediction accuracy for first cardiovascular events beyond current panels?
- ? What downstream genes modulated by GDF15 influence lifespan and neuroprotection in aging organisms?
- ? How do GDF15 levels as biomarkers differentiate heart failure subtypes based on inflammatory versus metabolic drivers?
Recent Trends
The field maintains 14,685 works with no specified 5-year growth rate.
High-citation papers from 1992-2020 dominate, including McPherron et al. (1997, 3921 citations) on TGF-β muscle regulation and Wang et al. (2006, 1357 citations) on cardiovascular biomarkers.
No recent preprints or news in the last 12 months indicate steady consolidation of GDF15 applications in inflammation and metabolic homeostasis.
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