Ageing - Can we live forever?

Abstract

Ageing is a multidimensional process of physical, psychological and social change. It is a universal process that can refer to cells that stopped dividing (cellular senescence), the process of becoming older (organismal ageing) or to the ageing of a population (population ageing). Organismal ageing is characterized by a progressive loss of physiological integrity a primary risk factor for major human pathologies, including neurodegenerative diseases cancer, diabetes and cardiovascular disorders. Ageing can be studied by analyzing the two sides of the “ageing coin”: supercentenarians and those who age prematurely. This can be done by studying the influence of genetics and the environment on individuals that become 100 years-old and beyond in comparison with those who suffer from progeroid syndromes and age faster. One common denominator of the ageing process is the accumulation of DNA damage throughout life. Most of the progeroid syndromes, such as Werner, Bloom and Cockayne Syndrome, are in fact consequence of failures in DNA repair. The integrity and stability of DNA are continuously challenged by both endogenous and exogenous threats. These include DNA replication errors, reactive oxygen species (ROS), UV-light and pollution.

Besides studying human ageing, the whole ageing process and its genetics can be analysed using model organisms. 35 years ago, the first genetic screen, using C.elegans worms, was designed to select for long-lived mutants. This was followed by many others, using other model organisms that helped discover a plethora of “ageing-genes”. Many of these are related to the maintenance and integrity of DNA, while others were identified as part of nutrient sensing pathways. Currently, ageing is being studied through several fronts, the different hallmarks of ageing. From genomic instability and epigenetics and stem cells, through telomeres, protein folding, mitochondrial function and intercellular communication.