Researchers have in recent years made inroads into the infrastructure and knowledge needed to investigate the molecular biology of aging in killifish. The various species of killifish occupy a good compromise position between short length of life and the degree to which their biochemistry is relevant to human aging. As an added bonus, there is a fair degree of variation in life span between different killifish species, allowing for comparative investigations of their genetics and cellular biology. Short-lived animals mean faster studies, more research conducted for any given amount of funding, but the further removed from humans the species is, the more likely it is that the output of any given study provides no useful insight to direct the study of aging in mammals. As in all things, there are trade-offs involved.
A favourite of fish hobbyists since the 1970s, killifish are gaining popularity among scientists who study ageing, and dozens of labs now house them. Elderly killifish - a couple of months old - show hallmarks of ageing. Their bright scales fade and their cognition wavers; many develop tumours. Lifespan-altering experiments that take years in mice and decades in primates can be over in months in killifish, which are also more closely related to humans than are fruit flies, nematodes and other short-lived lab organisms popular in ageing research. "It turns out to be the shortest-lived vertebrate that can be raised in captivity."
The turquoise killifish genome contains several clues to its peculiar, fleeting life. Valenzano and his colleagues found that variations in genes involved in nutrient sensing, DNA repair and ageing have been selected for during its evolutionary history. Such genes might prove instructive for ageing in longer-lived animals. One such is IGF1R, which has been linked to extreme longevity in bowhead whales, naked mole-rats and Brandt's bat. Genes linked to IGF1R vary between an extremely short-lived killifish lab strain and a wild variety that can live for twice as long. A similar difference between short-lived and longer-lived strains was also seen in a gene that has been linked to dementia in humans. "Maybe these genes are central hubs for regulating survival. In some species they can accelerate ageing, and in some they can slow it down."
Genetic-engineering experiments - such as creating knock-out fish that lack particular genes - are needed to confirm whether the genes pinpointed in these studies truly influence ageing. These tests are already under way. Earlier this year a team used CRISPR-Cas9 genome editing in 'proof-of-principle' experiments to alter several ageing-related genes in killifish. "We are excited at trying to make it live longer." The team is also screening drugs in killifish to see if any lengthen its lifespan or slow tissue degeneration.