The featured paper is from 2002 and is titled ‘Aging and Synaptic Plasticity: A Review’ by Bergado and Almaguer and freely available here. This is a review paper which grapples with a broad topic – the relationship between aging and a cellular process proposed as a basis for memory formation.
The aim of the paper is clearly stated – ‘describing how LTP is affected by aging’. However there is no method section for this paper. Instead there is a narrative type feel to the article with clear conclusions in each section, before the authors finish by examining possible therapeutic strategies for reversing LTP changes in aging. While this is a great way to get an overview of a complex subject area, a meta-analysis would have been well suited to reaching some sort of conclusion within the different sections.
Having said that, the review has a clear structure and this helps in tackling what is a very difficult question. One of the complexities of discussing aging and cognition is that there is an interplay between the individual’s genetics and their environment over the course of a lifetime. Thus the aging process is very much individualised and drawing broad conclusions on the population with such a process risks overgeneralising. In this sense though the authors have created a number of testable hypotheses which involve generalised and well established cellular processes increasing the likelihood that their discussion is meaningful.
The authors put the case forwards for Long Term Potentiation (LTP) and Long Term Depression contributing to neuronal plasticity. They then summarise evidence showing that LTP is impaired in aging. In order to examine the possible mechanisms for this, there are three sections under the rubric of ‘Possible Mechanisms of Impairment’, these being ‘Impaired induction’, ‘Impaired maintenance’ and ‘Impaired heterosynaptic reinforcement’. In terms of impaired induction the authors argue that the influence of glutamate is reduced in aging and that this could occur through a reduction of glutamate receptors in the cortex. The authors further argue that there is a move away from NMDA mediated calcium influx to mechanisms involving Voltage Dependent Calcium Channels. This imbalance in turn is argued to increase the rate at which newly formed memories fade. In terms of maintenance the authors argue that a reduction in protein synthesis and cell adhersion molecules with age will reduce the ability to maintain LTP. Finally the authors examine impaired heterosynaptic reinforcement. Their suggestion here is that since emotional or motivational states influence learning, they may be expected to have an effect on LTP. In this regards they highlight reductions in acetylcholine and Noradrenaline with aging as possible contributory mechanisms to reduced LTP. These hypotheses are both plausible and testable. The authors conclude by looking at therapeutic strategies for reversing age related changes in LTP. In light of the recent study on calorific restriction and its relation to verbal memory, the authors’ comment on the relationship between vit E and calorific restriction on LTP are interesting. They discuss trophic factors favourably.
This is a useful overview of an increasingly important subject area for therapeutics in aging.
Steps To Treatment = 5 (Theoretical models requiring empirical support then testing of appropriate therapeutic agents with regulatory approval and incorporation into policies)
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