GenAge entry for GDF11 (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Gene name (HAGRID: 309)

HGNC symbol: GDF11
Aliases: BMP11; BMP-11
Common name: growth differentiation factor 11

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Description

GDF11 is a morphogenic, blood circulating, cytokine that is part of the bone morphogenetic protein (BMP) family and TGF-beta gene superfamily. GDF11 is a myostatin-homologous protein that is involved in development. The encoded preproprotein is proteolytically processed to generate each subunit of the homodimer [4366].

GDF11 has been shown to have a potential anti-ageing role in mice as part of the ‘young blood’ theory [4369]. Circulating levels of GDF11 in mice normally decline with age and its depletion is associated with cardiac hypertrophy and other morbidities. Restoring systemic GDF11 levels by heterochronic parabiosis or systemic delivery of recombinant protein reverses age-related dysfunction in mouse skeletal muscle [4367] and boosts blood flow and neurogenesis in the brain [4370]. GDF11 levels have been shown to predict median life span in several mouse strains, with GDF11 levels showing high heritability [4368].

However, GDF11’s role in ageing is still controversial and later studies have questioned the initial findings. A screen of extracellular proteins attempting to identify factors involved in ageing in murine skeletal muscle satellite cells did not identify any GDF11 activity, conflicting with previous data [4371]. In humans, it was found that levels of MSTN, a homologue of GDF11, decline in healthy adult men throughout ageing but not GDF11. GDF11 and MSTN levels do not differ as a function of age in healthy women [4372]. GDF11 inhibited muscle regeneration in mice [4373] and supraphysiological levels of GDF11 lead to skeletal and cardiac muscle wasting [4500]. Furthermore, GDF11 levels appear to increase with age in human serum [4373]. In aged individuals with severe aortic stenosis individuals with higher levels of GDF11 are more likely to be frail and have diabetes or prior cardiac conditions [4372]. Further study is required to understanding these conflicting findings and better elucidate GDF11’s debated role in ageing.

Cytogenetic information

Cytogenetic band: 12q13.2
Location: 55,743,277 bp to 55,757,193 bp
Orientation: Plus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0001501; skeletal system development
GO:0001656; metanephros development
GO:0001657; ureteric bud development
GO:0008285; negative regulation of cell proliferation
GO:0010862; positive regulation of pathway-restricted SMAD protein phosphorylation
GO:0021512; spinal cord anterior/posterior patterning
GO:0031016; pancreas development
GO:0042981; regulation of apoptotic process
GO:0043408; regulation of MAPK cascade
GO:0045596; negative regulation of cell differentiation
GO:0048469; cell maturation

And 3 more GO terms

Cellular component:

GO:0005575; cellular_component
GO:0005615; extracellular space
GO:0005654; nucleoplasm
GO:0043231; intracellular membrane-bounded organelle
GO:0043234; protein complex

Function:

Show all GO terms

Protein interactions and network

No interactions in records.

Retrieve sequences for GDF11

ORF: ORF
CDS: CDS

Homologs in model organisms

Danio rerio: gdf11
Mus musculus: Gdf11
Rattus norvegicus: Gdf11