Via Ouroboros, I am directed to notice that the latest issue of Nature Insight covers aging science, and for the moment at least is open access - jump in and take a look. These promotional gaps in the journal pay walls don't tend to last all that long, so make make the most of it. For the attention deficit generation, there's even an audio podcast that outlines this research and its significance.
It is now clear that by tinkering with particular signalling pathways and by balancing nutrition, the lifespan of many organisms, including yeast, worms, flies and mice, can be extended. Crucially, the same tweaks often bring about substantial health benefits and seem to delay the onset of age-related diseases. Most of the pathways involved are evolutionarily conserved, so it is likely that some of this research will eventually benefit human health.
For many years, molecular biologists interested in regulatory mechanisms did not study ageing, as the tissue decline associated with ageing suggested a passive, entropic process of deterioration that occurred in a haphazard way. We know now, however, that the ageing process, like so many other biological processes, is subject to regulation by classical signalling pathways and transcription factors. Many of these pathways were first discovered in small, short-lived organisms such as yeast, worms and flies, but a remarkable fraction turn out to extend lifespan in mammals as well.
The budding yeast Saccharomyces cerevisiae is one of the most important model organisms used in ageing-related research. In comparison with other systems, the relative ease and rapidity with which longevity can be quantified in yeast has allowed rapid progress is defining the molecular mechanisms of ageing in this organism and the identification of dozens of factors that modify its longevity. How much of what we learn about ageing in yeast is relevant to people has become an important question. We do not yet know the answer, but the evidence so far suggests that although some aspects of ageing in yeast are specific to this organism, many of the most important features have been evolutionarily conserved in invertebrate species and rodents.
Increasing evidence points to telomeres and p53-mediated DNA damage signalling being core components that drive the senescent or apoptotic depletion of tissue stem-cell reserves and age-related tissue degeneration. Although such cellular checkpoint mechanisms contribute to the functional decline of highly proliferative tissues, how they would adversely affect the more quiescent tissues that are equally ravaged by the ageing process (such as heart, brain and liver) has been more difficult to rationalize. Here, we put forth a speculative model that posits a connection linking telomere damage and p53 activation with stem-cell and mitochondrial dysfunction. This model offers a unifying explanation of how telomeres influence the health of the ageing organism across diverse tissues with wide-ranging proliferative profiles.
Two important technical advances have provided new insight into the biology of brain ageing. Microarray technology has made global gene expression analysis possible in humans and model organisms, leading to the identification of evolutionarily conserved changes during ageing. Concurrently, improvements in functional brain imaging have afforded us an unprecedented view of the workings of large-scale cognitive networks in the ageing human brain. An important challenge is to unify these two levels of analysis to obtain a more global view of brain and organismal ageing in humans.
The finding that mortality at advanced ages can be postponed, and indeed is being postponed, resolved a millennia-old debate about whether survival could be extended among the elderly. The evidence published since 1994 is compelling. Unless radical breakthroughs are achieved, perhaps as a result of research on other species, humans will continue to suffer senescence - but the process is not intractable. Mortality has been postponed considerably, as a result not of revolutionary advances in slowing the process of ageing but of ongoing progress in improving health.