Omics · study · 2026
Lsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila
Listed in NCBI GEO
Mechanistic target of rapamycin complex 1 (mTORC1) senses amino acid availability to orchestrate metabolic processes critical for physiological homeostasis and organismal ageing 1.
Description
While mTORC1 preferentially regulates the translation of 5′-terminal oligopyrimidine (TOP) motif-containing mRNAs that predominantly encode ribosomal proteins (RPs) via the translational repressor 4E-BP 2, this mTORC1 function is resistant to rapamycin inhibition 3.
TOP mRNAs are exceptionally abundant, thus imposing a major translational burden on cells; yet how their translation is physiologically tuned and linked to longevity remain unexplored. Here we identify Lsp2, originally known as a storage protein 4, as an adipose effector of mTORC1 that modulates lifespan in Drosophila. Lsp2 is induced by essential amino acids (EAAs) via mTORC1.
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Genetic ablation of Lsp2 to blunt organismal response to protein diets drives robust lifespan extension without compromising key life-history traits such as reproduction. Translatomic profiling reveals that loss of Lsp2 selectively reduces global TOP mRNA translation in a 4E-BP-dependent manner, thereby extending lifespan via a mechanism distinct from rapamycin inhibition. Finally, Lsp2 adipokine promotes 4E-BP phosphorylation and acts systemically across tissues to shape the lifespan responses to dietary protein.
Collectively, our findings establish Lsp2 as a novel translational regulator of TOP genes that mechanistically couples physiological ribosomal protein synthesis with organismal longevity.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE297nnn/GSE297586 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE297586 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1265223 ncbi.nlm.nih.gov/bioproject/PRJNA1265223 ↗
project · from NCBI GEO
Topics
- Stated by source
- Drosophila melanogaster · Expression profiling by high throughput sequencing
- From keywords
- Life Sciences
- Inferred from text
- Biochemistry and cell biology 69%
Related
- Possibly the same asLsp2 links mTORC1 to TOP mRNA translation and lifespan in Drosophila
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE297586 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].anzsrc:group:3101 | enrichment · NCBI GEO | taxonomy-embedding@1.1.0 | title+keywords+description (69%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:7227 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |