Long-lived bats offer clues on diseases, aging

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The bat, a reservoir for viruses like Ebola, SARS and Nipah, has for decades stumped scientists trying to figure out how it is immune to many deadly bugs but a recent study into its genes may finally shed some light, scientists said on Friday.


Studying the DNA of two distant bat species, the scientists discovered how genes dealing with the bats’ immune system had undergone the most rapid change.

This may explain why they are relatively free of disease and live exceptionally long lives compared with other mammals of similar size, such as the rat, said Professor Lin-Fa Wang, an infectious disease expert at the Duke-NUS Graduate Medical School in Singapore who led the multi-centre study.

“We are not saying bats never get sick or never get infections. What we are saying is they handle infections a lot better,” Wang said in a telephone interview.

What was missing from both species of bats was a gene segment known to trigger extreme, and potentially fatal, immune reactions to infections, called the cytokine storm.

Cytokine storms end up killing not only offending viruses in the body, but the host’s own cells and tissues too.

Written By: Tan Ee Lyn
continue to source article at newsdaily.com

9 COMMENTS

  1. Humans already have sufficient DNA and other systems. We don’t need additional pharmaceutical swindles to try and keep up with other species immune and other systems. (Except perhaps if they can get humans to grow bat wings and fly.)

    First point is that the immune storm, sometimes fatal to humans, might be a crucial element in our species’ evolved strategy that prevents infected people from continuing social contact and increasing the risk of spreading the infection among the local population. Maybe the fact that bats do not range as widely as humans on this planet is a clue to the limitations of the bats’ alternative strategy. No wonder they’re so good at spreading ebola, rabies, and the Hendra virus.

    Second thing is that infectious diseases in humans, and probably most cancers, are a consequence of an impaired immune system and impaired DNA maintenance processes. Humans already possess reasonably good systems for dealing with this.

    All that’s required is to let those systems work without continuous disruption. That doesn’t require an effectively impossibly pharmaceutical development program. Just to stop the disruption. E.g. Toxin abuse from alcohol, tobacco, and ingesting excess amounts of those even more toxic substances like glucose and fructose.

    But there is obviously more money in the prospective pharmaceutical sales area, compared to just telling people not to be so stupid and to look after themselves.

  2. Conspiracy theory indicates irrational thinking, Pete; as does the assertion we should abandon medical intervention. By your reasoning penicillin & other drugs which have saved millions were a mistake? 
    The only part of your flawed argument I can agree with is eliminating intake of toxins where possible. But “even more toxic substances like glucose and fructose” is based on what research? 
    I do hope you don’t get a potentially fatal infection…

  3. It can be said that Antibiotic use might  be a bad thing , the rate of bacterial resistance to them might see the whole spectrum of antibacterials reduced to nothing in a very short time .Then again waiting for mutations in the genome that make humans immunity better could also be said to be a bad thing .

  4. Pete H, I get the impression that you aren’t a fan of pharmaceutical companies (from several threads) and that’s ok but it’s getting hard to tell if your comments are an impassioned plea to self-reliance and common sense regarding drug claims or whether you are descending into conspiracy…

    As Nodhimmi says, life would be rather different, uncomfortable and probably shorter without modern medicine, drugs included. The human DNA recipe is definitely not suited to living much longer than it takes to reproduce and raised the kids to a moderate age. Disease burden has shifted to ages beyond which it affects evolutionary fitness – there’s a reason more than 80% of lifetime health spending (in the UK at least) is in the last 6 weeks of life.

    Also, glucose is kinda the major carbohydrate in use in the body so calling it a toxin is not really correct. In any case, toxin exposure is a trade off – you’d be chasing down sodium nitrite in bacon (too yummy to avoid!), not living in Devon due to radon or aluminium adsorbants in vaccines. Even too much salt may kill you but you won’t find anyone (sane) cutting it out entirely.

  5. I would also add that finding ways to precisely modify the inflammatory response in the face of overwhelming infection or inflammation is one of the holy grails of immunology – imagine the implications for organ and bone marrow transplant survival if we can keep the peace between host and donor? The tools we currently have are somewhat crude.

    In any case, as RichardofYork already mentioned, finding out how animals such as these bats and crocodiles manage to survive such infectious environments would be far from a swindle if it reduces our reliance on antimocrobial chemicals. Waiting for the human genome to DIY the solution just isn’t gonna happen in a setting where such premature death and suffering isn’t acceptable…

  6. Yes, possibly more inflammatory than justified.

    But conspiracies aren’t necessarily irrational. No need to be afraid of them. They really do exist sometimes. There’s plenty of extraordinary yet rational conspiracies around if you know where to look.

    Plus there’s plenty of pseudo-conspiracies: really bad situations that weren’t consciously intended by their creators and beneficiaries, but which otherwise might as well be conspiracies. If anything they might be anti-conspiracies where participants don’t actively conspire to do anything, instead they inadvertently collectively don’t look too closely into things and so fail to fully comprehend. No need to ask too many questions or rock the boat too violently, just in case they find out anything they might not like or which risks undermine personal benefits.

    With antibiotics there is some form of conspiracy like this. Obviously they are a good thing, as long as they remain effective. Marketing them in some situations is extremely profitable and not illegal, any more than selling tobacco products.

    I’m probably still alive owing to antibiotics, thanks to a staph infection (spider bite – routine in Australia) that I was too unconcerned about to take seriously. The sweet young chick at the clinic sent me home with 2 aspirins and no phone number. I went back a day or so later and the 70+ year grumpy old man filling in for her said he’d seen many who were less affected than me who’d died. He wanted to call an ambulance on me. Ended getting 2 weeks on intra-venous.

    I don’t know what might be done for anyone who acquires a similar aggressive colony of the many resistant staphs floating around. Increasingly likely over the next 10 years if they’re unfortunate enough to drop by the local hospital. Chances are that the lack of effectiveness due to anti-biotic resistance won’t be obvious for a day or so. Too late for many.

    Having read Ben Goldacre he makes a good argument that both situations: the availability and affordability of anti-biotics, and their excessive use leading to their growing ineffectiveness, are attributable to the pharmaceutical industry.

    And medical intervention involves much more than treating symptoms with physicians collecting bonus points towards their next skiing holiday via pharmaceutical scrip returns. At least it should. I think that the popularity of homeopaths and other quackery is a direct consequence of most physicians being at least no less effective than quackery for most things.

    One reason is that many people actually visit physicians for serious problems. Mostly physicians are just screening for real problems, or referrals to specialists. My own GP says the most prevalent complaint he faces is people complaining they’re tired all the time, but he can find nothing obviously wrong. If quack treatments are just placebos then he’s operating on an equal footing with the quacks. Possibly less than equal footing – at least with the aroma therapy and acupuncturists the patient gets a chance to lie down and have a rest while they’re being ‘treated’.

    Regarding human genomes and lifespan. There’s a reasonably plausible theory that humans are very much longer lived than is commonly accepted. At least for those who survive childhood and young adulthood and warfare. Not greatly different to present day life expectancy in civilised countries. The evolutionary argument is that genetic constraints require relative youthfulness in reproductive adults, but for prehistoric and pre-literate human cultures crucially dependent on accumulated technology for survival then a high availability of relatively elderly adults might be a more optimum strategy for raising children. This idea isn’t compatible with elderly adults normally, slowly, and predictably becoming decrepit, at least in their natural environment. (Which is now believed to involve a very much smaller lifetime exposure to glucose and other simple sugars compared to the modern day elderly.)

    A clue might be those who die suddenly from Alzhiemers in late old age, but who were entirely normal until near the end. Most people succumb slowly, often starting in middle age and maybe taking a decade until becoming senile. But those who are physically and mentally very active in their old age somehow offset the degeneration.

    So it’s possible that humans already possess a genome that enables a sufficiently long and healthy life to provide maximum benefits for their grandchildren and other descendants.

    And regarding glucose toxicity. You’ll find that many common and very simple substances essential for life are toxic, sometimes in quite small doses that only marginally exceed what is normal for the circumstances humans are adapted to. You mention salt. But oxygen and water are good examples. (Oxygen toxicity mostly affects industrial divers and miners, water toxicity affects anyone who exercises in the heat and drinks too much – both can cause very rapid death.)

    Glucose may yet turn out to be the most devastating toxin in human history – in terms of its slow but chronic impact on people. There’s an extraordinary amount of research on this now accumulating.

    I’ve got nothing against bat immunology but it always irritates me that journalists or others reporting any newsworthy biological research imply that it’s all worth the expense because there’s going to be some pill at the end of the line. Especially when it’s unlikely that we’ll see much serious money going towards research that might conclude that people should stop doing something that is already a money spinner for suppliers, or which obviates many of the pharmaceutical industry profit lines.

  7. Pete H, don’t worry – I’m generally a subscriber to the view that the paranoid are just those in possession of all the facts. I appreciate your point about those who do not always ask the uncomfortable questions but I find it hard to believe (in a scientific/medical setting) that this is the norm – if an uncomfortable question arises, we must present the hypothesis and look for supporting evidence. Finding out you were right is an ego boost few would pass up. Not asking questions because you benefit from the status quo is a different thing, as you say.

    You’re right that the marketability of antibiotics is partly to blame for their downfall. However, bugs are quite good at dodging whatever we throw at them. The most recent 2 antibiotics I recall hitting the shelves (daptomycin and linezolid in the early 2000s) both lasted less than 18 months before resistance was detected. At least nowadays we are in a situation where we appreciate what antimicrobials we have and (hopefully) only use them appropriately. Even the drug companies can’t argue with this: if there is widespread resistance to their product, nobody will buy it. I don’t think your comparison with tobacco is quite valid as you don’t generally ask you doctor what brand of cigarette you should smoke :P You’re possibly being a bit hard on your GP if you’re saying most of what he does is no better than placebo – unlike a quack, (s)he has a duty to you and an evidence base to apply (and hopefully contribute to). Finding nothing obviously wrong with someone is still an important negative finding!

    Anyway, the article relates to the immune system of bats helping them to survive otherwise devastating reactions to infectious disease. I am fascinated by your point that a long lifespan may be due to a different strategy to family-rearing success but it’s not quite the topic being discussed.

    I read something a long while back (forgotten where) relating to maximising lifespan by calorie restriction – is that at all related to what you are saying about glucose intake? Or are you referring to the triggering of insulin resistance and eventually diabetes (and all its myriad consequences) through pancreatic beta-cell death (in which case I accept your use of the word ‘toxin’)? Sugar is a funny thing since we are driven to consume it in relative
    excess, unlike (generally) salt, oxygen and water which are taken in excess either accidentally or because we consciously override our ‘need.’ For what it’s worth, I think the article is essentially saying that we may have a better model to emulate than our traditional animal experimentee, the rat. If ‘big pharma’ comes up with a perfect suite of immunomodulators, I’ll be glad – they’ll still have to prove it’s cost-effective!

    Lastly, there is serious research into not doing what makes other people money – some of which we’ve already discussed, such as: cutting out junk-food, not misusing antibiotics, not smoking (although this does have the carrot/stick-factor of the lung cancer link) and recently (July 21st issue) the British Medical Journal ran an issue with several articles debunking sports supplements and energy drinks. So no need to abandon all hope :)

  8. It may be that bats have only a vestigial immune system. The reason they apparently survive infections might be because they rely partly on other animals immune systems.

    Definitely worth studying. But don’t expect any new drug designs to follow.

    Regarding glucose intake:

    Glucose is inherently damaging to structural tissues and internal cellular mechanisms. It’s like continually throwing spanners into the works of a complex factory. Resulting damage is repairable, but takes time and resources. And the specific damage and consequences are unpredictable. Some machinery will be more susceptible than others. And consequences will vary randomly.

    When glucose molecules encounter proteins there is a statistical probability, though very small, that they will randomly bind to any available polymer chains and cause those polymer strings to cross-link to themselves and other adjacent proteins. To some extent this is normal and controlled during protein assembly, because it affects protein shape and resulting structural and functional properties. But chronic excess exposure to glucose causes random effects to proteins. Mostly to make proteins dysfunctional. Or even worse, in that all proteins eventually become dysfunctional but dysfunctional glycated proteins may also become relatively more difficult even to recycle. So they clog things up, lock up resources, and don’t perform their intended function while interfering with other processes.

    I think of it as like sulphur vulcanising rubber to produce car tyres. Good for that specific purpose, but less useful where more flexibility and stretchiness is required. Like when it’s inside a rubber tree doing whatever it was evolved to do. And the human equivalent in the stretchy lining of coronary arteries, or the proteins that control the shape and mechanical properties of corneas. Coronary arteries are subject to the most intensive exposure to glucose via the immense volume of high pressure blood that passes through them. Especially when that blood is chronically saturated in glucose. (Which it is for many people.)

    Normal diet (high in products containing sugar and wheat etc.) will inevitably overwhelm systems evolved to grapple with continual glycation damage. The first line of defence is insulin and other hormonal responses which cause glucose to be sequestered in much less toxic forms as glycogen, adipose storage, or by directly oxidising rapidly for energy. (i.e. the ‘sugar high’ in kids.) There’s plenty of other glycation mitigating systems, most of which probably haven’t been identified or conceived of.

    Calorie restriction will diminish glucose exposure. This positive outcome may be the entire effect on longevity in all mammals studied. But longevity is only relevant to humans because only humans seem to have evolved to live long enough to rear multiple generations of their own progeny’s progeny, a consequence of intelligence. There’s no long-term evolutionary advantage to a rat raising its great-grandchildren because they can’t talk and tell stories to them.

    If my understanding of caloric restriction is correct then people who practise it might live longer, but their bodies and minds will slow down to adapt to the diminished available energy. They will probably live longer but experience less, get less done, and have a lower quality of life. Calorie restriction might even just be triggering a form of hibernation or famine response, a genetic artefact like the mammalian diving reflex. Not really of much value in modern humans.

    There’s nothing inherently bad about short term glucose exposure provided the body’s mitigation systems haven’t yet been overwhelmed – which takes a long time. The cumulative effect, once mitigation systems become overwhelmed (probably indicated by insulin resistance), is comparable to lead poisoning.

    It’s certainly a good thing to understand bats’ immune systems. Something I think Richard Dawkins has often stated is that evolution is often mistakenly assumed to be directional and towards increasing perfection. So we assume there’s something inherently ‘better’ about human physiology. Bats may have stumbled across a unique solution to managing high energy metabolism by trading off immunity from viruses.

    Owing to the energy demands of flight bats slam through much more oxygen and fuel per unit body volume compared to humans. Fuel being glucose or fats, fats being directly absorbed by insect eaters or converted from fructose by fruit eaters, or from fat converted from glucose converted from protein in the vampire bats! To be able to fly they have to eat a lot. And to be able to drop their metabolism hanging around between feeds.
    Staying slightly on topic: It’s a completely off the wall idea but maybe bats’ physiology has evolved to more aggressively mitigate this glycation and oxidation damage, especially to their DNA, seeing they would incur such very high exposure via their very high fuel burn compared to other mammals. This damage might exceed that of viral infections.

    Their evolved immune strategy might be to ignore many infections and instead just cope with them and clean up the aftermath. Giving their parasites more of a chance to adapt without significantly harming their host. Which might explain why they’re such good carriers of so many infectious diseases that infect other species.

    Bats may be off-loading their immune burden on to other species, via those other species aggressive cytokine responses. i.e. Many viruses might have evolved, via infectious transitions through other host species, to be benign enough to avoid provoking the aggressive immune responses in their hosts. Except when the viruses respond to immanent death of their host, when they sometimes go beserk with a last ditch emergency reproduction – perhaps triggered by a drop in blood glucose indicating stress.

    Bats might indirectly benefit from this normally benign viral behavior  Enough to get by without much more than a token immune response. Which might be just enough to keep viral reproduction in line most of the time. A bat that does succumb to an exploding viral infection is most likely experience problems during flight (maximum energy demand) and so will drop out of the sky up to 500km from home – with little chance of spreading contagion to other bats.

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