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  • Anti-Aging Studies Reveal Longer Lives on the Horizon

    • Scientists discover how the brain’s hypothalamus controls ageing – and manage to slow it down

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    If you are reading this and you don’t smoke, then your major risk factor for dying is probably your age. That’s because we have nearly eliminated mortality in early life, thanks to advances in science and engineering. But despite this progress, we still haven’t worked out how to eliminate the damaging effects of ageing itself.

    Now a new study in mice, published in Nature, reveals that stem cells (a type of cell that can develop into many other types) in a specific area of the brain regulate ageing. The team even managed to slow down and speed up the ageing process by transplanting or deleting stem cells in the region.

    The gap between generations is levelling out.
    from www.shutterstock.com

    Ageing poses an important challenge for society. By 2050, there will be as many old people (age 65+) as children (under 15) on Earth for the first time. This change is reflected in unprecedented stress on our health and social care systems. Understanding how we can keep ourselves in good health as we age is becoming increasingly important.

    The mechanisms that keep organisms healthy are relatively few in number and conserved between species, which means we can learn a lot about them by studying animals such as mice. Among the most important are senescent cells – dysfunctional cells which build up as we age and cause damage to tissue – chronic inflammation and exhaustion of stem cells. These mechanisms are thought to be connected at the cell and tissue level. As with a ring of dominoes, a fall anywhere can trigger a catastrophic collapse.

    Vanishing cells

    The researchers behind the new paper were studying the mouse hypothalamus, which we’ve known for some time controls ageing. This almond-sized structure at the centre of the brain links the nervous and endocrine (hormone) systems. The hypothalamus helps regulate many basic needs and behaviours including hunger, sleep, fear and aggression. In the human brain, initiation of behaviours is usually complex, but if you flee in blind panic or find yourself in a blazing rage, then your hypothalamus is temporarily in the driving seat.

    The hypothalamus in the human brain. Life Sciences Database

    The team looked at a specialised group of stem cells within the hypothalamus and monitored what happened to them as cohorts of mice aged. Mice normally live for about two years but they found that these cells began to disappear by about 11 months. By 22 months, they had vanished completely. The rate at which the stem cells was lost closely correlated with ageing changes in the animals, such as declines in learning, memory, sociability, muscle endurance and athletic performance.

    But correlation doesn’t mean causation. To find out if the decline was causing these ageing changes, they deleted stem cells using a specially engineered virus that would only kill them in the presence of the drug Ganciclovir. In 15-month-old mice, receiving this drug combination destroyed 70% of their hypothalamic stem cells. They prematurely displayed signs of ageing and died roughly 200 days earlier as a result. That’s significant as mice only live for about 730 days.

    The group also implanted hypothalamic stem cells from newborn mice into middle-aged animals. In this case, the animals became more social, performed better cognitively and lived about 200 days longer than they otherwise would have.

    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.

    Elixir of youth?

    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?
    Evgeny Atamanenko

    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.

    The ConversationWhether 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.

    Richard Faragher, Professor of Biogerontology, University of Brighton

    This article was originally published on The Conversation. Read the original article.

    Bees Can Have False Memories Too

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    You might remember getting your first car – but would be hard pressed to give the right day or time of year – swearing that it was April while the bill of sale says that it was June, but you’re pretty sure that first date gone wrong was with the new car you bought in April. If any of this sounds familiar at all, it’s called conflating your memory. People have actually been known to remember things different from how they happened, or they recall events that hadn’t happened at all.

    Manufactured memories aren’t just unique to people, however. Scientists at MIT two years ago induced false memories of trauma in lab mice for a study. A year later, with the use of light, they were able to manipulate the brains of their test subjects, turning their painful memories into more pleasant ones.

    Now, a new experiment at Queen Mary University of London has shown that this plasticity of memory exists in insects too. After performing an experiment that would make Pavlov proud, the researchers Kathryn Hunt and Lars Chittka concluded that bumblebees will sometimes fuse certain details of past memories into newer ones. The research was published Friday in Current Biology.

    “I suspect the phenomenon may be widespread in the animal kingdom,” researcher Dr. Chittka said in a written statement to the Christian Science Monitor.

    Something of this nature seems a bit difficult to carry out – gauging what mice think is hard enough, let alone a stinging insect. Yet, several years ago, scientists also found that bees were capable of recognizing human faces – using the same internal mechanisms that allow them to recognize different flowers. To do their research, Chittka and Dr. Hunt first classically trained the bumblebees, giving them a small reward for visiting two artificial flowers. One was solid yellow, while the other contained rings of black. This was setting up a control. As long as the bee landed on both flowers, it was still given an offering of sugar. After the trial, the bees were presented with a choice of either the yellow or striped flower types, but the researchers threw in a third new choice. The third combines characteristics of the first two, mixing both yellow-and-white rings. On the first day, the bees consistently landed on the first two flowers, the ones that offered a reward.

    Within one to three days following their initial training, something different happened – the bees became confused incorrectly flew to the yellow-and-white flower (on up to 50 percent of the tests). While they had never seen such a pattern, they internally associated the stripes with the reward, combining their previous knowledge to form a new memory.

    “Bees might, on occasion, form merged memories of flower patterns visited in the past,” Chittka said. “Should a bee unexpectedly encounter real flowers that match these false memories, they might experience a kind of deja-vu and visit these flowers expecting a rich reward.”

    Because bumblebee brains have a rather small capacity, Chittka suspects that these manufactured memories are actually shorthand notes to the brain of what is important to remember – rewards being produced by visiting both a striped and a yellow flower. Both ideas quickly become condensed into one.

    “In bees, for example, the ability to learn more than one flower type is certainly useful,” Chittka said, “as is the ability to extract commonalities of multiple flower patterns. But this very ability might come at the cost of bees merging memories from multiple sequential experiences.”

    Chittka has been researching memory in bumblebees for over two decades. As they can be raised in a lab setting, they make ideal test subjects.

    Don’t let the name fool you. “They are [also] exceptionally clever animals that can memorize the colors, patterns, and scents of multiple flower species – as well as navigate efficiently over long distances,” Chittka said.

    While studies done in the past assumed animals had been incapable of performing tasks when they failed to do them in clinical tests, Chittka’s research is one of the first to make patterns out of the mistakes. What it reveals is that many animals have a mechanism for their memories that may be substantially more complex than we imagined.

    “I think we need to move beyond understanding animal memory as either storing or not storing stimuli or episodes,” Chittka said. “The contents of memory are dynamic. It is clear from studies on human memory that they do not just fade over time, but can also change and integrate with other memories to form new information. The same is likely to be the case in many animals.”

    Hopefully, the research will lead to a better understanding of what false memories really are and why we sometimes cling to them so tightly. Think of them as evolutionary links to a diverse and distant past, rather than a brain misfire. Most of all, think of why you take in the particular details you remember, and looking at what you left out may enhance the past experience you had, letting you relive it to an extent.

    “Errors in human memory range from misremembering minor details of events to generating illusory memories of entire episodes,” Chittka said. “These inaccuracies have wide-ranging implications in crime witness accounts and in the courtroom, but I believe that – like the quirks of information processing that occur in well known optical illusions – they really are the byproduct of otherwise adaptive processes.”
    James Sullivan
    James Sullivan is the assistant editor of Brain World Magazine and a contributor to Truth Is Cool and OMNI Reboot. He can usually be found on TVTropes or RationalWiki when not exploiting life and science stories for another blog article.