Living long and well: prospects for a personalized approach to the medicine of ageing

Research into ageing and its underlying molecular basis enables us to develop and implement targeted interventions to ameliorate or cure its consequences. However, the efficacy of interventions often differs widely between individuals, suggesting that populations should be stratified or even individualized. Large-scale cohort studies in humans, similar systematic studies in model organisms as well as detailed investigations into the biology of ageing can provide individual validated biomarkers and mechanisms, leading to recommendations for targeted interventions. Human cohort studies are already ongoing, and they can be supplemented by in silico simulations. Systematic studies in animal models are made possible by the use of inbred strains or genetic reference populations of mice. Combining the two, a comprehensive picture of the various determinants of ageing and ‘health span' can be studied in detail, and an appreciation of the relevance of results from model organisms to humans is emerging. The interactions between genotype and environment, particularly the psychosocial environment, are poorly studied in both humans and model organisms, presenting serious challenges to any approach to a personalized medicine of ageing. To increase the success of preventive interventions, we argue that there is a pressing need for an individualized evaluation of interventions such as physical exercise, nutrition, nutraceuticals and calorie restriction mimetics as well as psychosocial and environmental factors, separately and in combination. The expected extension of the health span enables us to refocus health care spending on individual prevention, starting in late adulthood, and on the brief period of morbidity at very old ag

Antimicrobial and Osseointegration Properties of Nanostructured Titanium Orthopaedic Implants

The surface design of titanium implants influences not only the local biological reactions but also affects at least the clinical result in orthopaedic application. During the last decades, strong efforts have been made to improve osteointegration and prevent bacterial adhesion to these surfaces. Following the rule of “smaller, faster, cheaper”, nanotechnology has encountered clinical application. It is evident that the hierarchical implant surface micro- and nanotopography orchestrate the biological cascades of early peri-implant endosseous healing or implant loosening. This review of the literature gives a brief overview of nanostructured titanium-base biomaterials designed to improve osteointegration and prevent from bacterial infection

Phase-locking characteristics of limbic P3 responses in hippocampal sclerosis

Amplitudes of the P3 recorded invasively from the medial temporal lobe (MTL-P3) have been reported to be reduced on the side of a mediotemporal epileptogenic focus. This reduction has been attributed to the massive cell loss within the hippocampus associated with hippocampal sclerosis. It has remained unclear how functional connectivity between the hippocampus and rhinal cortex, as well as within the hippocampus, is altered in hippocampal sclerosis. To investigate this issue, we analyzed to what extent stimulus-related phase-locking and power changes within the low-frequency range (2-30 Hz) and within the gamma band (32-48 Hz), as well as rhinal-hippocampal phase synchronization contribute to the averaged MTL-P3 potentials. Event-related responses were recorded via bilateral depth electrodes in epilepsy patients with unilateral hippocampal sclerosis, who performed a visual oddball experiment. On the contralateral (nonsclerotic) side, successful target detection was associated with an increase of power and phase locking of hippocampal activity in both the low-frequency range and in the gamma range. Besides, there were rhinal-hippocampal synchronization enhancements in the theta and gamma range. On the ipsilateral (sclerotic) side, the event-related power increase in the low-frequency range had almost disappeared, a finding likely to be explained by the loss of principle neurons. However, low-frequency phase-locking, rhinal-hippocampal synchronization, as well as event-related power changes in the gamma range persisted ipsilaterally, although there were differences in temporal and spectral characteristics. These findings support the hypothesis that functional connectivity between hippocampus and rhinal cortex, as well as intrahippocampal connectivity, are partially preserved in hippocampal sclerosis. © 2004 Elsevier Inc. All rights reserved

Incorporation of Amino Acids with Long-Chain Terminal Olefins into Proteins

The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants of pyrrolysyl-tRNA synthetase (PylRS). Nε-heptenoyl lysine was incorporated for the first time using the known promiscuous variant PylRS(Y306A/Y384F), and Nε-pentenoyl lysine was incorporated in significant yields with the novel variant PylRS(C348A/Y384F). This is the only example of rational modification at position C348 to enlarge the enzyme’s binding pocket. Furthermore, we demonstrate the feasibility of our chosen amino acids in the thiol-ene conjugation reaction with a thiolated polysaccharide

Incorporation of Amino Acids with Long-Chain Terminal Olefins into Proteins

The increasing need for site-specific protein decorations that mimic natural posttranslational modifications requires access to a variety of noncanonical amino acids with moieties enabling bioorthogonal conjugation chemistry. Here we present the incorporation of long-chain olefinic amino acids into model proteins with rational variants of pyrrolysyl-tRNA synthetase (PylRS). Nε-heptenoyl lysine was incorporated for the first time using the known promiscuous variant PylRS(Y306A/Y384F), and Nε-pentenoyl lysine was incorporated in significant yields with the novel variant PylRS(C348A/Y384F). This is the only example of rational modification at position C348 to enlarge the enzyme's binding pocket. Furthermore, we demonstrate the feasibility of our chosen amino acids in the thiol-ene conjugation reaction with a thiolated polysaccharide.status: publishe

Living Long and Well: Prospects for a Personalized Approach to the Medicine of Ageing.

Research into ageing and its underlying molecular basis enables us to develop and implement targeted interventions to ameliorate or cure its consequences. However, the efficacy of interventions often differs widely between individuals, suggesting that populations should be stratified or even individualized. Large-scale cohort studies in humans, similar systematic studies in model organisms as well as detailed investigations into the biology of ageing can provide individual validated biomarkers and mechanisms, leading to recommendations for targeted interventions. Human cohort studies are already ongoing, and they can be supplemented by in silico simulations. Systematic studies in animal models are made possible by the use of inbred strains or genetic reference populations of mice. Combining the two, a comprehensive picture of the various determinants of ageing and 'health span' can be studied in detail, and an appreciation of the relevance of results from model organisms to humans is emerging. The interactions between genotype and environment, particularly the psychosocial environment, are poorly studied in both humans and model organisms, presenting serious challenges to any approach to a personalized medicine of ageing. To increase the success of preventive interventions, we argue that there is a pressing need for an individualized evaluation of interventions such as physical exercise, nutrition, nutraceuticals and calorie restriction mimetics as well as psychosocial and environmental factors, separately and in combination. The expected extension of the health span enables us to refocus health care spending on individual prevention, starting in late adulthood, and on the brief period of morbidity at very old age