Many swear that the key to a healthy life is good food. Washed down with a glass of red wine, you'd think a hearty meal would be the perfect recipe not only for a healthy life, but a long one, too. However, experimental manipulation in several organisms — from yeast to non-human primates — has shown that a restriction in the intake of calories can extend lifespan; a calorie-restricted diet also reduces the number of cases of age-related disorders such as heart disease and cancer. On page 298, Laura Bordone and Leonard Guarente outline the metabolic changes that result from restricted calorie intake, and attempt to relate them to the NAD-dependent histone deacetylase activity of the SIRT1 enzyme.

A key contributor to the ageing process is oxidative damage, caused by the destructive nature of reactive oxygen species. In an ideal scenario, damaged cells are removed by apoptosis, but this process is determined by the balance between death-promoting caspases, inhibitor of apoptosis (IAP) proteins and IAP antagonists. By virtue of their baculoviral IAP repeat (BIR) motifs, IAPs directly inhibit caspases, but IAPs also contain RING domains, which mediate the transfer of ubiquitin onto various substrates. Obvious targets for ubiquitin-directed proteolysis are caspases, but IAPs might target many other substrates — including themselves — for ubiquitylation, as is reviewed by David L. Vaux and John Silke on page 287.

Apoptosis is well known to shape life, and so we have almost come full circle — from ageing, to death, to the beginnings of life. In this issue, and over the forthcoming months, we aim to look at developmental biology from a cell biological perspective, in a series of articles that starts with a Review by Joan E. Hooper and Matthew P. Scott on Hedgehog signalling (see page 306).