Ageing is not a passive, disorganized process of deterioration, as biologists once thought. Like many biological processes, it is controlled by signalling pathways and transcription factors. Mutations in certain genes can slow down ageing and lengthen lifespan in model organisms, such as yeast, flies and the nematode Caenorhabditis elegans. Pathways that extend life expectation include insulin/IGF-1 pathway, Chronic dietary restriction, the amino acid and nutrient sensor TOR, AMP kinase a nutrient and energy sensor, sirtuins, and telomere length. Nutrient sensors support growth and reproduction but slow down when there are harsh conditions.
Kenyon The genetics of ageing 2010 Nature vol 464 pp 504-512
The budding yeast Saccharomyces cerevisiae is the of the most important models in ageing research. Its short lifespan and the ease by which both dividing and non-dividing cells can be studied has led to much progress in defining the molecular mechanisms of ageing and the factors that affect longevity in yeast. Many of these – including dietary restriction, the protein kinase TOR (target of rapamycin) and sirtuins – have now been shown to be evolutionarily conserved across species and are some of the most promising targets for anti-ageing drugs.
Kaeberlein Lessons on longevity from budding yeast 2010 Nature vol 464 pp 513-519.
Ageing-related pathways have been characterized in various organisms, but it is unclear how they interact during the ageing process. Now, studies of mutant mice and people with genetic disorders seem to indicate that three pathways – genome maintenance, DNA damage signalling and metabolic regulation connect during ageing. One possible model is that damage to telomeres (which protect chromosomes from degradation) and impaired DNA repair activate the tumour-suppressor protein p53, leading to cell death, cell senescence, or arrest of the cell division cycle, together with impaired mitochondrial function. This leads to further DNA damage, feeding into a cycle of decline-Overall, the pools of tissue stem cells become smaller, making it difficult to maintain the proper function of the body’s organs.
Sahin & DePinho Linking functional decline of telomeres, mitochondria and stem cells during ageing 2010 Nature vol 464 pp 520-528
During ageing in humans, the brain undergoes structural and physiological changes and cognitive capacity declines. The technological advances of DNA microarray analysis and functional imaging of the brain have enabled researchers to study ageing at a deeper level, by characterizing the changes that occur in brain gene expression and large-scale cognitive networks as a person ages. In addition, many of the pathways that have been identified to control ageing in various organisms have also been found to modulate the pathology and cognitive decline in animal models of neurodegenerative disorders. Together, these lines of research are improving our understanding of normal and pathological ageing of the brain and how this leads to cognitive decline, providing the first steps to treating and, perhaps, preventing such conditions. A. Bishop, T. Lu & B. A. Yankner Neural mechanisms of ageing and cognitive decline 2010 Nature vol 464 pp 528-535
Over the past couple of centuries, the lifespan of humans has been extended considerably and is still increasing by hours each day. Remarkably, people are reaching old age in better health. This progress is largely a result of better medical care, rising standards of living and healthier lifestyles. Research by demographers, epidemiologists and biomedical researchers suggests that humans can live to even greater ages, and in good health. It is clear that further improvement of health among elderly people will be aided by a better understanding of the root causes of ageing and by targeting these for intervention.
Vaupel Biodemography of human ageing 2010 Nature vol 464 pp 536-542.

Martin Eastwood
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