The Telomeric Complex and Metabolic Disease

Abstract

The attrition of telomeres is believed to be a key event not only in mammalian aging, but also in disturbed nutrient sensing, which could lead to numerous metabolic dysfunctions. The current debate focuses mainly on the question whether telomere shortening, e.g., as a heritable trait, may act as a cause or rather represents a consequence of such chronic diseases. This review discusses the damaging events that ultimately may lead or contribute to telomere shortening and can be associated with metabolic diseases.

Keywords: diabetes; leucocyte telomere length; metabolic diseases; obesity telomere shortening.

Figure 1

Interplay between physiological and pathophysiological metabolic states and telomerase activity. Dietary compounds, healthy lifestyle, and anti-diabetic therapies inhibit telomerase activity and lead to increased leukocyte telomere length (LTL). In contrast, obesity, increased fat mass, and type-2 diabetes result in decreased leukocyte telomere length, possibly through oxidative stress and inflammatory pathways. Telomere length can directly influence insulin sensitivity. BMI: body mass index; WHR: waist-to-hip ratio; Med. Diet: Mediterranean Diet; ROS: reactive oxygen species; hTERT: human telomerase reverse transcriptase; hTERC: non-coding telomerase RNA component; hTEP1: human telomerase-associated protein 1; PPAR: peroxisome proliferator-activated receptor; GLP-1: glucagon-like peptide 1; DPP4: Dipeptidyl peptidase-4.