Fight Aging!

Antagonistic pleiotropy is the name given to a particular view on the evolution of aging. Natural selection will favor optimization of capacity in early life, when reproduction is possible, but not the optimization of capacity in late life. Given a system in which the decline of aging is already happening to some degree, there will be further selection of processes that work well at the outset but cause harm later on in life. The adaptive immune system is an example of the type: it is highly effective in youth, due to its capacity for memory, but runs down and malfunctions in the later life context of trying to maintain memory of a lifelong exposure to countless varieties of pathogen.

Researchers here present evidence for the cellular maintenance processes of autophagy to be pleiotropic in this way, at least in nematode worms. In this species autophagy works well in the context of a youthful low level of damage, but then becomes actively harmful in the later life context of high levels of damage and dysfunction. Early life capacity for reproduction has a much greater influence on the traits that are selected than late life capacity, and this sort of thing is the outcome.

Ageing in worms mainly results from the direct action of genes and not from random wear and tear or loss of function, and the same is likely to be true in humans, according to research. The study shows that normal biological processes which are useful early on in life, continue to 'run-on' pointlessly in later life causing age-related diseases. The deteriorative part of ageing, called 'senescence', is the main cause of disease and death worldwide as it leads to dementia, cancer, cardiovascular disease, and chronic obstructive pulmonary disease, but scientists have struggled to identify what causes it.

To address this, researchers have focused on discovering the basic principles of ageing by studying simple animals such as Caenorhabditis elegans, a nematode worm used in this study which lives on fruit, and dies of old age after only 2-3 weeks. Specifically, they focused on autophagy, where body cells consume their own biomass to recycle components and extract energy. They found that the worms' intestine consumes itself (autophagy) to create the yolk needed for eggs, and in elderly worms, this process causes severe deterioration of the intestine and obesity from a build-up of pooled fats. In turn, this further impacts on the health of the worm by promoting growth of tumours in the uterus, and shortens lifespan.

"This really surprised us since autophagy is usually thought to protect against ageing rather than cause it. It seems that worms crank-up autophagy, which is considered good, to maximise reproductive success, which is good too, but they end up overdoing it, causing senescence." When useful biological programmes run-on in later life, they can become disease-causing 'quasi-programmes'. Such programmes were recently proposed and the findings support that they are indeed a major underlying cause of ageing. This does not mean that aging is programmed but instead, that it is a continuation of developmental growth driven by genetic pathways to the point where these becomes harmful. Other examples include an increase in blood pressure causing hypertension and an increase to the eyes' near vision point causing long-sightedness and a need for reading glasses.

Link: http://www.lancaster.ac.uk/news/genes-drive-ageing-making-normal-processes-damaging