Additional file 1: Figure S1. of Frailty is associated with the epigenetic clock but not with telomere length in a German cohort

Distribution of main analysis variables. Shown are the histograms (overlay: fitted Normal distribution) of difference-based DNAm age acceleration (A, B), relative telomere length (C, D), and frailty index (E, F; based on one instance of the multiple imputation procedure). Left plots refer to dataset 1 (consecutively recruited subsample of source study; n = 969), right plots to dataset 2 (case-cohort subsample of source study; n = 851). (PDF 1818 kb

Additional file 1: Table S1. of Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort

Associations of single CpG sites with all-cause mortality. (XLSX 12 kb

HSP70-HSP90 chaperone networking in protein-misfolding disease

Molecular chaperones and their associated co-chaperones are essential in health and disease as they are key facilitators of protein-folding, quality control and function. In particular, the heat-shock protein (HSP) 70 and HSP90 molecular chaperone networks have been associated with neurodegenerative diseases caused by aberrant protein-folding. The pathogenesis of these disorders usually includes the formation of deposits of misfolded, aggregated protein. HSP70 and HSP90, plus their co-chaperones, have been recognised as potent modulators of misfolded protein toxicity, inclusion formation and cell survival in cellular and animal models of neurodegenerative disease. Moreover, these chaperone machines function not only in folding but also in proteasome-mediated degradation of neurodegenerative disease proteins. This chapter gives an overview of the HSP70 and HSP90 chaperones, and their respective regulatory co-chaperones, and explores how the HSP70 and HSP90 chaperone systems form a larger functional network and its relevance to counteracting neurodegenerative disease associated with misfolded proteins and disruption of proteostasis