The effect of telomere length, a marker of biological aging, on bone mineral density in elderly population.

UNLABELLED: Telomere length (TL), as a reflection of aging and inflammatory processes, may be associated with bone mineral density (BMD). This study examines the association between TL and BMD cross-sectionally and the rate of bone loss over a 4-year period in 1,867 Chinese elderly community living subjects. After adjusting for confounding factors, no association was observed with BMD or bone loss. The decline in BMD with aging is not reflected by corresponding changes in telomere length. INTRODUCTION: Bone mineral density (BMD) is influenced by the dynamics of aging, inflammatory, and bone remodeling processes. Telomere length (TL) is a reflection of the former two processes and may also be associated with bone loss. METHODS: Hip BMD was measured in 1,867 Chinese elderly community living subjects and the relationship between leukocyte TL measured using quantitative real-time polymerase chain reaction, and bone loss after 4 years was examined. RESULTS: Women had greater bone loss than men. In women, age of menopause, menarche, estrogen treatment/replacement therapy, and history of previous fracture were also among the significant covariates. However, in multivariate analyses, TL was not associated with BMD in either sex. CONCLUSIONS: TL was not associated with either baseline BMD or bone loss over 4 years and accounted for less than 1.6% of the baseline BMD.

Telomeres and frailty.

Associations between telomere length and various chronic diseases associated with ageing have led to the suggestion that telomere length may be an ageing biomarker. At the clinical level, the suggestion of using measurements of frailty as a measure of biological ageing has also been suggested. This study examines the hypothesis that telomere shortening may form the biological basis for frailty, using data obtained from a health survey of 2000 men and women aged 65 years and over, living in the community, and followed up for 4 years to determine survival. Frailty was measured using the frailty index, a summation of deficits covering physical, psychological, and functional domains. Telomere length was measured in 976 men and 1030 women, using real-time quantitative polymerase chain reaction. Women were more frail than men but had longer telomere length. In men only, there was a negative association between telomere length and age and a positive association between frailty index and mortality after adjusting for age. There was no correlation between telomere length and frailty index in either sex. While telomere length may be a biomarker of cellular senescence, this relationship may not be extrapolated to the functional level represented by the frailty phenotype.

Selective effects of an essential sulfhydryl group on the activation of dopamine- and guanine nucleotide-sensitive adenylate cyclase.

Treatment of membranes from the dog caudate nucleus with sulfhydryl alkylating agents, N-ethylmaleimide and p-chloromercuribenzoate, results in selective inhibition of dopamine-sensitive adenylate cyclase activity that can be distinguished from effects on basal enzyme activity. Fifty per cent inhibition of dopamine-sensitive adenylate cyclase activity was observed in the presence of 10(-5) M N-ethylmaleimide and 3 X 10(-6) M p-chloromercuribenzoate. N-Ethylmaleimide (10(-5) M or less) also inhibited GTP- and NaF-stimulated adenylate cyclase activity, but had no effect on basal adenylate cyclase activity (assayed in the presence of magnesium) and on enzyme activity assayed in the presence of manganese. The reducing agents dithiothreitol, 2-mercaptoethanol, glutathione, and cysteine had no inhibitory effect on dopamine-sensitive adenylate cyclase activity. Pretreatment of membranes with guanyl-5'-yl imidodiphosphate or guanosine 5'-O-(3-thio)triphosphate prior to incubation with N-ethylmaleimide prevented the inhibitory effect of N-ethylmaleimide on adenylate cyclase activity. The results suggest that a reactive sulfhydryl group in the domain of the GTP-binding protein is important for the coupling of the components of the dopamine-sensitive adenylate cyclase complex in brain.

Regulation of vitamin K-dependent carboxylation.

Vitamin K-dependent carboxylation activity measured with pentapeptide substrate (Phe-Leu-Glu-Glu-Leu) gradually decreases upon in vivo injection of vitamin K to vitamin K-deficient rats. A decrease in pentapeptide carboxylation can also be observed by the in vitro addition of antibodies against prothrombin and other vitamin K-dependent proteins to the soluble system derived from vitamin K-deficient rat liver microsomes. In both cases, adding back in vitro partially decarboxylated vitamin K-dependent proteins or purified hepatic prothrombin precursor restores the level of pentapeptide carboxylation. After warfarin treatment, a 3-fold increase in carboxylation results, which can be abolished by giving cycloheximide along with the warfarin. However, the resulting decreased activity is restored by the in vitro addition of partially decarboxylated vitamin K-dependent proteins. These data are consistent with the hypothesis that (after warfarin treatment) increased peptide carboxylation is primarily due to activation of the system by precursor proteins, rather than synthesis of an increased amount of enzyme.

Soluble enzyme system for vitamin K-dependent carboxylation.

The vitamin K-dependent carboxylating system has been solubilized by Lubrol PX or Triton X-100 treatment of vitamin K-deficient rat liver microsomes. As obtained from vitamin K-deficient rat liver, this soluble preparation is dependent upon the in vitro addition of vitamin K1 for carboxylating activity. The enzyme system is complex and is dependent upon NADH and dithiothreitol for maximum activity. While detergents used to solubilize the enzyme complex do markedly inhibit the activity of the system, the solubilized system is still highly responsive to vitamin K addition and can be used for further study of the carboxylating enzyme system. The requirement for dithiothreitol and the inhibition by p-hydroxymercuribenzoate indicate the involvement of an --SH enzyme in the carboxylating system.