TY  - JOUR
AB  - Glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) are associated with the surface of eucaryotic cells only through a covalently coupled carboxy-terminal GPI glycolipid structure which is anchored at the outer leaflet of plasma membranes. This mode of membrane association may be responsible for the recent observations that full-length GPI-APs harbouring the complete GPI anchor are (i) released from isolated rat adipocytes in vitro and (ii) expressed in rat and human serum. The upregulation of the adipocyte release in response to increased cell size and blood glucose/insulin levels of the donor rats and downregulation of the expression in serum of insulin resistant and diabetic rats have been reconciled with enhanced degradation of the full-length GPI-APs released into micelle-like complexes together with (lyso) phospholipids and cholesterol by serum GPI-specific phospholipase D (GPI-PLD).Here by using a sensitive and reliable sensing method for full-length GPI-APs, which relies on surface acoustic waves propagating over microfluidic chips, the upregulation of (i) the release of the full-length GPI-APs CD73, alkaline phosphatase and CD55 from isolated adipocyte plasma membranes monitored in a "lab-on-the-chip" configuration, (ii) their release from isolated rat adipocytes into the incubation medium and (iii) the lipolytic cleavage of their GPI anchors in serum was demonstrated to increase with age (3-16 weeks) and body weight (87 - 477 g) of (healthy) donor rats. In contrast, the amount of full-length GPI-APs in rat serum, as determined by chip-based sensing, turned out to decline with age/body weight. These correlations suggest that age-/weight-induced alterations (in certain biophysical/biochemical characteristics) of plasma membranes are responsible for the release of full-length GPI-APs which becomes counteracted by elevated GPI-PLD activity in serum. Thus, sensitive and specific measurement of these GPI-AP-relevant parameters may be useful for monitoring of age-related cell surface changes, in general, and diseases, in particular.
AU  - Müller, G.
AU  - Ussar, S.
AU  - Tschöp, M.H.
AU  - Müller, T.D.
C1  - 59754
C2  - 48984
CY  - Elsevier House, Brookvale Plaza, East Park Shannon, Co, Clare, 00000, Ireland
TI  - Age-dependent membrane release and degradation of full-length glycosylphosphatidylinositol-anchored proteins in rats.
JO  - Mech. Ageing Dev.
VL  - 190
PB  - Elsevier Ireland Ltd
PY  - 2020
SN  - 0047-6374
ER  - 

TY  - JOUR
AB  - We conducted a case-control genome-wide association study (GWAS) of human longevity, comparing 664,472 autosomal SNPs in 763 long-lived individuals (LLI; mean age: 99.7 years) and 1085 controls (mean age: 60.2 years) from Germany. Only one association, namely that of SNP rs4420638 near the APOC1 gene, achieved genome-wide significance (allele-based P=1.8×10(-10)). However, logistic regression analysis revealed that this association, which was replicated in an independent German sample, is fully explicable by linkage disequilibrium with the APOE allele ɛ4, the only variant hitherto established as a major genetic determinant of survival into old age. Our GWAS failed to identify any additional autosomal susceptibility genes. One explanation for this lack of success in our study would be that GWAS provide only limited statistical power for a polygenic phenotype with loci of small effect such as human longevity. A recent GWAS in Dutch LLI independently confirmed the APOE-longevity association, thus strengthening the conclusion that this locus is a very, if not the most, important genetic factor influencing longevity.
AU  - Nebel, A.*
AU  - Kleindorp, R.*
AU  - Caliebe, A.*
AU  - Nothnagel, M.*
AU  - Blanche, H.*
AU  - Junge, O.*
AU  - Wittig, M.*
AU  - Ellinghaus, D.*
AU  - Flachsbart, F.*
AU  - Wichmann, H.-E.
AU  - Meitinger, T.
AU  - Nikolaus, S.*
AU  - Franke, A.*
AU  - Krawczak, M.*
AU  - Lathrop, M*
AU  - Schreiber, S.*
C1  - 6759
C2  - 29222
SP  - 324-330
TI  - A genome-wide association study confirms APOE as the major gene influencing survival in long-lived individuals.
JO  - Mech. Ageing Dev.
VL  - 132
IS  - 6-7
PB  - Elsevier
PY  - 2011
SN  - 0047-6374
ER  -