As people who research ageing like to quip: the best thing you can do to increase how long you live is to pick good parents. After all, it has long been recognised that longer-lived people tend to have longer-lived parents and grandparents, suggesting that genetics influence longevity.
Author
Bradley Elliott
Senior Lecturer in Physiology, University of Westminster
Complicating the picture, however, is that we know that the sum of your lifestyle, specifically diet and exercise, also significantly influences your health into older age and how long you live. What contribution lifestyle versus genetics makes is an open question that a recent study in Nature has shed new light on.
Scientists have long known that reducing calorie intake can make animals live longer. In the 1930s, it was noted that rats fed reduced calories lived longer than rats who could eat as much as they wanted. Similarly, people who are more physically active tend to live longer. But specifically linking single genes to longevity was until recently a controversial one.
While studying the lifespan of the tiny worm C elegans at the University of California, San Francisco, Cynthia Kenyon found that small changes to the gene that controls the way that cells detect and respond to nutrients around them led to the worms doubling their lifespan. This raises new questions: if we know that genetics and lifestyle affect how long you live, which one is more important? And how do they interact?
To try to tease out the effects of genetics versus lifestyle, the new study in Nature examined different models of caloric restriction in 960 mice. The researchers specifically looked at classical experimental models of caloric restriction (either 20% or 40% fewer calories than control mice), or intermittent fasting of one or two days without food (as intermittent fasting is popular in people looking to see the positive benefits of caloric restriction).
Because we now know that small genetic variations affect ageing, the researchers specifically used genetically diverse mice. This is important for two reasons. First, as laboratory studies on mice are normally performed on genetically very (very!) similar mice, this allowed the researchers to tease out the effects of both diet and genetic variables would have on longevity.
Second, humans are highly diverse, meaning that studies on genetically near-identical mice don't often translate into humanity's high genetic diversity.
The headline finding was that genetics appeared to play a larger role in lifespan than any of the dietary restriction interventions. Long-lived types of mice were still longer lived despite dietary changes.
Diet counts, but genes count more
And while shorter-lived mice did show improvements as a result of dietary restrictions, they didn't catch up to their longer-lived peers. This suggests that there's truth to the "pick good parents" joke.
Caloric restriction models still increased lifespans across all the types of mice, with the 40% restriction group having improved average and maximum lifespans compared with the 20% group.
And the 20% group showed improvements in both group average and maximum length of lives compared with the control group. It's just the effects of genetics were larger than the effect of the dietary interventions.
While all the caloric restriction models resulted in increased lifespan in the mice on average, in the most extreme caloric restriction model tested (40% less group) changes that could be seen as physical harms were observed. These included reduced immune function and losses in muscle mass, which outside of a predator- and germ-free laboratory environment could affect health and longevity.
There are some important caveats in studies like this. First, it's not known if these results apply to humans.
As with most caloric restriction research in mice, the restricted feeding groups were fed 20% or 40% less than a control group who ate as much as they wanted. In humans, that'd be like assuming people eating every meal every day at a bottomless buffet is "normal". And people who do not eat from limitless trays of food are "restricted feeding". That's not an exact parallel to how humans live and eat.
Second, although exercise wasn't controlled in any way in this study, most groups did similar amounts of running in their in-cage running wheels except the 40% caloric restriction group who ran significantly more.
The researchers suggested that this extra exercise in the 40% group was the mice constantly hunting for more food. But as this group did so much more exercise than the others, it could also mean that positive effects of increased exercise were also seen in this group alongside their caloric restriction.
So, while we can't pick our parents or change the genes we inherit from them, it is interesting to know that specific genetic variations play a significant role in the maximum age we can aspire to.
The genetic cards we're dealt dictate how long we can expect to live. Just as important in this study, however, lifestyle interventions such as diet and exercise that aim to improve lifespan should be effective regardless of the genes we have.
Bradley Elliott receives funding from the Physiological Society, the British Society for Research on Ageing, the Altitude Centre, and private philanthropic individuals, and has consulted for industry and government on longevity research. He is on the Board of Trustees of the British Society for Research on Ageing.
