“These experiments also provided clues to how the hypothalamic stem cells were being lost in the first place. The implantation only worked when the stem cells had been genetically engineered to be resistant to inflammation. It seems that, as the animals aged, chronic, low-grade inflammation in the hypothalamus increased.
“This inflammation is probably caused either by the accumulation of senescent cells or surrounding neurons entering a senescent-like state. Inflammation kills the hypothalamic stem cells because they are the most sensitive to damage. This then disrupts the function of the hypothalamus with knock-on effects throughout the organism. And so the dominoes fall.
“The ultimate goal of ageing research is identifying pharmaceutical targets or lifestyle interventions that improve human health in later life. While this is a study in mice, if we can show that the same mechanisms are at play in humans we might one day be able to use a similar technique to improve health in later life. But this remains a long way in the future.
“Other interventions, such as removing senescent cells, also improve health, extending life by up to 180 days in mice. A logical next step is to see if these interventions ‘stack’.
“Could we stop unsuccessful ageing in humans with the same technique?
“The study also demonstrates that hypothalamic stem cells exert major effects through secreting miRNAs, which control many aspects of how cells function. MiRNAs are short, non-coding RNAs – a molecule that is simpler than DNA but can also encode information. When miRNAs were supplied alone to mice lacking stem cells they actually showed similar improvements to those who received stem-cell treatment.
“The delivery of miRNAs as drugs is still in its infancy but the study suggests potential routes to replenishing a hypothalamus denuded of stem cells: preventing their loss in the first place by controlling the inflammation. This might be achieved either through the development of drugs which kill senescent cells or the use of anti-inflammatory compounds.
“The research is important because it elegantly demonstrates how different health maintenance mechanisms interact. However, one downside is that only male mice were used. It is well known that the structure of the hypothalamus differs markedly between the sexes. Drugs and mutations which extend lifespan also usually show markedly different potency between males and females.
“Whether humans will ever be able to live significantly longer than the current maximum lifespan of 125 years is hard to tell. But it seems the greatest barrier to a healthy later life is no longer the rate of progress but the speed with which we can turn our growing knowledge of the biology of ageing into drugs and lifestyle advice.”