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Related Experiment Video

Updated: Jun 9, 2026

The Replica Set Method: A High-throughput Approach to Quantitatively Measure Caenorhabditis elegans Lifespan
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Identifying PDAP1 as a Biological Target on Human Longevity: Integration of Mendelian Randomization, Cohort, and Cell

Tianzhichao Hou1,2, Zimo Sha3,4, Qi Wang1,2

  • 1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Geriatric Medical Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Aging Cell
|April 11, 2025
PubMed
Summary

Researchers identified key proteins and gene transcripts influencing human lifespan. PDAP1 (PDGFA-associated protein 1) showed a significant negative effect on longevity, accelerating cellular senescence and increasing mortality risk.

Keywords:
PDAP1drug targetslongevitymediation analysismendelian randomizationproteomicstissue‐specific analysistranscriptomics

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Area of Science:

  • Genetics and Molecular Biology
  • Aging Research
  • Biomedical Science

Background:

  • Understanding factors influencing lifespan is crucial for developing interventions for healthy longevity.
  • Genetic and protein-level factors play significant roles in determining human life expectancy and aging processes.

Purpose of the Study:

  • To identify causal genetic and protein targets affecting human longevity.
  • To elucidate biological pathways implicated in healthy aging and lifespan.
  • To explore potential therapeutic targets for extending healthy life.

Main Methods:

  • Integrated Mendelian randomization, cohort studies (UK Biobank), and in vitro experiments.
  • Utilized large-scale genetic (eQTLGen, GTEx) and proteomic datasets.
  • Performed multi-trait colocalization and cellular senescence assays.

Main Results:

  • Identified 14 plasma proteins and 9 whole-blood transcripts with causal effects on longevity.
  • Discovered a negative longevity effect for LPA, PDAP1, DNAJA4, and TMEM106B.
  • PDAP1 (PDGFA-associated protein 1) demonstrated strong genetic evidence linking it to reduced lifespan via hormonal, adiposity, and epigenetic aging pathways.
  • Elevated blood PDAP1 levels correlated with increased all-cause mortality and reduced life expectancy.
  • In vitro studies confirmed PDAP1's role in accelerating cellular senescence.

Conclusions:

  • PDAP1 is a significant factor negatively impacting human lifespan, potentially through mechanisms involving hormonal balance, adiposity, and epigenetic aging.
  • The study highlights novel drug targets and biological pathways for interventions aimed at promoting healthy longevity.
  • PDAP1 emerges as a key molecular player in regulating human lifespan and cellular aging processes.