Metabolism and proteostasis: at the intersection of inflammation- associated decline in healthspan

As the global research community endeavours to precipitously discover ways to prevent or treat disease in humans, attention is turning towards pursuits that will enable not only for long life, but critically longer lives that are healthy and meaningful. The process of ageing is unburdened by the evolutionary constraints that function to promote healthy procreation until around thirty years of age in humans, indicating, that along with genetics, multifactorial environmental mechanisms contribute to the ageing process of healthy individuals. Genetic models, dietary interventions, and drug treatments have all been shown to increase lifespan in mammals. But a longer life does not mean a healthier life, and to date, no discovery has even suggested immortality can be achieved in higher eukaryotes. In fact, numerous studies imply that there is an upper limit to human lifespan. There is a growing consensus that low level systemic inflammation, that is more prevalent in the elderly, and increases an individual’s chance of cardio- and neurovascular diseases associated with ageing, is the factor behind ‘healthy’ ageing. What causes this so called inflammageing is a judicious area of study, and as scientists and pharmaceutical companies develop better, broader, and more efficient treatments for human disease, greater numbers of researchers are looking to study the phenomenon of health span. At a cellular level, interventions targeting extended lifespan have given us clues as to what is occurring molecularly, for example, dietary restriction, systemically reduces metabolism, with lower levels of the proinflammatory markers that categorise inflammageing. This opinion piece will look specifically at how metabolic and proteinogenic processes dysfunction at a cellular level, to contribute to reduced health span, and how genetics, lifestyle, and therapeutics targeting these pathways are a rapidly expanding field of scientific research.