Frailty Status in Older Adults Is Related to Alterations in Indoleamine 2,3-Dioxygenase 1 and Guanosine Triphosphate Cyclohydrolase I Enzymatic Pathways

J Am Med Dir Assoc. 2017 Dec 1;18(12):1049-1057. doi: 10.1016/j.jamda.2017.06.021. Epub 2017 Aug 8.

Abstract

Background: Frailty is a multidimensional syndrome correlated to the loss of homeostasis and increased vulnerability to stressors, which is associated with increase in the risk of disability, comorbidity, hospitalization, and death in the elderly. It is based on the interplay of physiological, psychological, social, and environmental factors.

Objectives: Because aging involves a detrimental immune response, this work aimed to assess the possible role of chronic low-grade immune stimulation on frailty status in the elderly.

Methods: Biomarkers involved in indoleamine 2,3-dioxygenase 1 and guanosine triphosphate cyclohydrolase I enzymatic pathways (namely neopterin, tryptophan, kynurenine, phenylalanine, tyrosine, and nitrite) were analyzed in a population of Spanish older adults aged 65 years and above, and their relationships with frailty status were evaluated.

Results: Significant increases in neopterin levels, kynurenine/tryptophan ratio, and phenylalanine/tyrosine ratio, and significant decreases in tryptophan, nitrite and tyrosine concentrations in frail individuals compared with nonfrail persons were obtained. Significant correlations were also observed between immune biomarkers, indicating they change in parallel, thus, pointing to interrelated causes. Besides, reference ranges for a number of immune biomarkers in the population of robust older adults were established for the first time.

Conclusions: Results obtained in the present study are consistent with the idea that frailty status in the elderly is associated with an additional degree of immune stimulation, manifested in a more intense disturbance of indoleamine 2,3-dioxygenase 1 and guanosine triphosphate cyclohydrolase I pathways than in nonfrail or prefrail older adults.

Keywords: Frailty; immune activation; kynurenine/tryptophan ratio neopterin; nitrite; phenylalanine/tyrosine ratio.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / immunology*
  • Analysis of Variance
  • Biomarkers / blood
  • Cohort Studies
  • Confidence Intervals
  • Enzyme Assays
  • Enzyme-Linked Immunosorbent Assay / methods
  • Female
  • Frailty / enzymology*
  • Frailty / immunology
  • Frailty / physiopathology
  • Geriatric Assessment / methods*
  • Guanosine Triphosphate / analysis
  • Guanosine Triphosphate / metabolism*
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / analysis
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Male
  • Prognosis
  • Reference Values
  • Risk Assessment
  • Spain
  • Surveys and Questionnaires

Substances

  • Biomarkers
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Guanosine Triphosphate