The different players in longevity

Listen to audio

To set the scene for this year's lectures, I'll start with a very comprehensive review by Lopez-Otin and colleagues(Cell 153: 1194-1217, 2013) which attempts to define the marks of aging, the less smiling face of longevity, not just cerebral, but general. Longevity is an important issue that cannot be thought of in terms of the more or less rapid degradation of organisms from an arbitrarily proclaimed "ideal age". On the contrary, it must be seen in the context of the instability of living structures and the constant renewal of organisms at the molecular and cellular levels, as has often been asserted in recent years. To this must be added the evolution of epigenetically modified individuals, in the structure of their chromatin, as well as that of their neural networks, at the synaptic and morphological levels. This distinction between ageing and adaptation through individuation, and the need to identify the part played by adaptation in ageing, is important because it draws a distinction between organisms that have a history and a memory, and those that live in the immediacy of the present moment.

Of course, the distinction is never so clear-cut, and epigenetics and individual adaptation can be found in even the simplest organisms, such as C. elegans and its 300 or so neurons. In this approach to longevity, based on an understanding of the renewal and/or evolution of structures, we are obliged to distinguish between organs that are subject to continuous cell renewal, such as the intestine, the skin or the haematopoietic system, and those that are only partially renewed, such as the brain. This organ, in fact, is a mixture of post-mitotic neurons and neurons which renew themselves from stem cells, not to mention other cell types (astrocytes, oligodendrocytes, macrophages, vascular endothelial cells) which will be the subject of a lecture or two in the next few years. As we can see, our approach to brain longevity will include many of the themes we've covered in previous years. I'd like to come back to them if necessary, even though we'll be tackling some new questions together.

In the article I referred to, Lopez-Otin and his colleagues define aging in terms of the functional decline that affects all living organisms. The article begins with an observation that we'll be able to take on board over the coming days, and concerns the link between cancer and aging from the point of view of the accumulation of lesions at the genetic, cellular and organic levels; an accumulation that only transforms physiology into pathology (for the pathological aspects of aging) above a certain threshold. And since we're talking about physiology, i.e. homeostasis, we have to assume that any intervention in these processes necessarily leads to a reaction, or regulation. In fact, homeostasis can be defined as a system of regulations that keep variations in the elements of a physiological whole within limits compatible with normality (i.e. health).