A test bed that swims Leibniz Institute on Aging

A fish with the briefest of lifespans may just end up teaching us how to live longer. Inhibiting the effects of certain genes turns out to lengthen their lifespan by as much as 15 per cent.

The African turquoise killifish has one of the shortest lifespans of all vertebrates: it reaches the ripe old age of only three to twelve months.

That short life expectancy – as well as the huge variation among individuals – makes it perfect for studying longevity.


Experiments that would take three years in a mouse take just six months in the killifish, says Alessandro Cellerino at the Scuola Normale Superiore in Pisa, Italy.

The killifish’s short lifespan stems from its life cycle in the wild. In Zimbabwe and Mozambique, the fish live in pools that only exist in the rainy season. During the dry season, adults die and their embryos go into a suspended state, encased in dry mud, until the pools fill again.

Cellerino’s team looked at differences in gene expression of individual fish that lived to different ages.

The study involved 152 male fish. The team took cell samples from fish at 10 weeks and 20 weeks old and froze them. Once the fish died, they compared gene expression in the shortest- and longest-lived fish.

They found that genes vital to a cell’s energy production are less active in young killifish that go on to be long-lived, and that inhibiting the proteins those genes make with a drug extends lifespan.

Gene expression differed much more at 10 weeks than at 20 weeks, showing that conditions favouring longevity are set during early adulthood. One of the most significant differences was in a group of genes involved in respiration inside mitochondria, cell components involved in generating energy.

When the team inhibited the products of those genes, targeting the so-called mitochondrial respiratory chain complex I with a chemical called rotenone, they prolonged lifespan by up to 15 per cent.

“This study supports the hypothesis that mitochondria, the batteries of the cells, are determinants in the ageing process,” says Joao Passos at the Newcastle University Institute for Ageing, UK. “This and other studies offer us clues about potential interventions to ameliorate the ageing process.”

But inhibiting mitochondrial activity to try to extend lifespan has not yet been tested in mammals such as mice, let alone humans.

Journal reference: Cell Systems, DOI: 10.1016/j.cels.2016.01.014