Publications by authors named "W Seinen"

Various models for ageing, each focussing on different biochemical and/or cellular pathways have been proposed. This has resulted in a complex and non-coherent portrayal of ageing. Here, we describe a concise and comprehensive model for the biochemistry of ageing consisting of three interacting signalling hubs.

View Article and Find Full Text PDF
Article Synopsis
  • Despite extensive research, the exact cause of Alzheimer's disease (AD) is still unknown, leading to a new hypothesis focusing on the enzyme carnitine palmitoyl transferase-2 (CPT2) as a key player in the disease.
  • CPT2, found in the inner mitochondrial membrane, is vital for fatty acid metabolism and is particularly sensitive to hydrogen peroxide, which is produced in excess by major AD risk factors.
  • The inhibition of CPT2 due to increased hydrogen peroxide levels may contribute to the symptoms of AD, offering new insights for potential therapeutic strategies.
View Article and Find Full Text PDF

The purpose of this article is to investigate the role of the AMP-kinase pathway (AMPK pathway) in the induction of a concomitant set of health benefits by exercise, numerous drugs, and health ingredients, all of which are adversely affected by ageing. Despite the AMPK pathway being frequently mentioned in relation to both these health effects and ageing, it appears challenging to understand how the activation of a single biochemical pathway by various treatments can produce such a diverse range of concurrent health benefits, involving so many organs. We discovered that the AMPK pathway functions as an integrated stress response system because of the presence of a feedback loop in it.

View Article and Find Full Text PDF

Preclinical development of new biological entities (NBEs), such as human protein therapeutics, requires considerable expenditure of time and costs. Poor prediction of pharmacokinetics in humans further reduces net efficiency. In this study, we show for the first time that pharmacokinetic data of NBEs in humans can be successfully obtained early in the drug development process by the use of microdosing in a small group of healthy subjects combined with ultrasensitive accelerator mass spectrometry (AMS).

View Article and Find Full Text PDF