A-kinase anchor protein 17A (AKAP-17A) (721P) (B-lymphocyte antigen) (Protein XE7) (Protein kinase A-anchoring protein 17A) (PRKA17A) (Splicing factor, arginine/serine-rich 17A) [CXYorf3] [DXYS155E] [SFRS17A] [XE7]

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The transcript expression levels of HNRNPM, HNRNPA0 and AKAP17A splicing factors may be predictively associated with ageing phenotypes in human peripheral blood.

Dysregulation of splicing factor expression is emerging as a driver of human ageing; levels of transcripts encoding splicing regulators have previously been implicated in ageing and cellular senescence both in vitro and in vivo. We measured the expression levels of an a priori panel of 20 age- or senescence-associated splicing factors by qRT-PCR in peripheral blood samples from the InCHIANTI Study of Aging, and assessed longitudinal relationships with human ageing phenotypes (cognitive decline and physical ability) using multivariate linear regression. AKAP17A, HNRNPA0 and HNRNPM transcript levels were all predictively associated with severe decline in MMSE score (p = 0.007, 0.001 and 0.008 respectively). Further analyses also found expression of these genes was associated with a performance decline in two other cognitive measures; the Trail Making Test and the Purdue Pegboard Test. AKAP17A was nominally associated with a decline in mean hand-grip strength (p = 0.023), and further analyses found nominal associations with two other physical ability measures; the Epidemiologic Studies of the Elderly-Short Physical Performance Battery and calculated speed (m/s) during a timed 400 m fast walking test. These data add weight to the hypothesis that splicing dyregulation may contribute to the development of some ageing phenotypes in the human population.

MeSH Terms

  • Aged
  • Aging
  • Antigens
  • Cellular Senescence
  • Cognitive Dysfunction
  • Correlation of Data
  • Female
  • Hand Strength
  • Heterogeneous-Nuclear Ribonucleoprotein Group M
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Humans
  • Male
  • Membrane Glycoproteins
  • Mental Status and Dementia Tests
  • Physical Functional Performance
  • Predictive Value of Tests
  • RNA Splicing Factors
  • Walking Speed

Keywords

  • Biomarkers
  • Cognitive decline
  • Splicing factors