Lifestyle is a threat to gut bacteria: Ötzi proves it, study shows

The intestinal microbiome is a delicate ecosystem made up of billions and billions of microorganisms, bacteria in particular, that support our immune system, protect us from viruses and pathogens, and help us absorb nutrients and produce energy.

The industrialization process in Western countries had a huge impact on its content. This was confirmed by a study on the bacteria found in the intestine of Ötzi, the Iceman who, in 1991, emerged from the ice of the Ötztal Alps, where Italy borders with Austria. Scientists of Eurac Research examined samples of the mummy's bacteria, confirming the findings of the researchers of the University of Trento who had analyzed the genome of intestinal microorganisms of over 6500 individuals from all continents.

Previous studies by the University of Trento had demonstrated that there is a connection between the microbiome's bacterial content and the increase, in Western countries, of obesity, autoimmune and gastrointestinal diseases, allergies and other complex conditions. In the study that appeared today in Cell Host & Microbe, researchers from Cibio of the University of Trento and Eurac in Bolzano/Bozen demonstrated that the differences between Western and non-Western or prehistoric microbiome lie in the decrease of some types of bacteria that process complex and vegetal fibers in the intestine.

That may have been caused by the Westernization process. Changes in diet, which is now higher in fat and low in fibers, a sedentary lifestyle in an urban setting, the development of new hygiene habits and the widespread use of antibiotics and other medical products have, with no doubt, made our life safer, but impacted the delicate balance of our microbiome.

About the study

The scientists of Eurac Research in Bolzano/Bozen sequenced the Iceman's DNA and were able to identify his set of bacteria, while the researchers of the University of Trento compared it with the microbiome of contemporary non-Westernized populations (from Tanzania and Ghana in particular), which are not used to processed food and have non-Westernized hygiene practices and lifestyle. Their findings were surprising.

The study focused, in particular, on Prevotella copri, a microbe that, when is found in our intestine, is usually the most represented. P. copri is present in 30% of Western individuals.

"First of all, we found out that P. copri it is not a monotypic species but is composed of four distinct but similar clades," explained Nicola Segata, coordinator of the study with Adrian Tett of Cibio of the University of Trento. "We then noticed that at least three of these four clades are almost always present in non-Westernized populations, but are much less prevalent in Westernized individuals. And when it is so, there usually is only one of the four clades. We postulated that the complex process of Westernization had a considerable impact on the gradual disappearance of this bacterium. Our hypothesis was confirmed by the analysis of ancient samples of DNA that were made available by Frank Maixner of the Institute for Mummy Studies at Eurac Research. The Iceman's guts contained three of the four clades of P. copri. And the four clades were also co-present in fossilized stool samples from Mexico that are more than one thousand years old. We still do not know what are the biomedical consequences of these changes of the microbiome which has evolved considerably in recent decades while the human body it colonizes has remained genetically practically unchanged for centuries,"

"Through these 'ancient' samples," continued Tett, "we were able to study the evolution of these clades and now we know that they genetically delineated with the human species and before the initial human migrations out of the African continent."

The study is the result of close collaboration with the research group of Albert Zink and Frank Maixner at Eurac Research in Bolzano/Bozen. Their team was responsible for the collection and pre-analysis of the Iceman's DNA samples. "The relation between the evolution of the human species and the diversity of intestinal microorganisms, as a field of research, is still rather unexplored, but can yield important results in the future through the analysis of ancient DNA. For this reason, finding more advanced and less invasive techniques to obtain and analyze DNA from human remains is one of the major areas of research at Eurac" concluded the microbiologist of Eurac Research Frank Maixner.

What do you need to know about Toxic Shock Syndrome?

What do you need to know about Toxic Shock Syndrome?

Toxic shock syndrome is a rare multisystem disease with many widespread symptoms. It is caused by a toxin that is produced and secreted by the bacterium Staphylococcus Aureus. Often staphylococcus aureus is blamed for toxic shock syndrome but it also can happen due to group A streptococcus (strep) bacteria. These bacteria are commonly found in some areas on our bodies such as nose, armpit, skin, groin, or vagina of every one in three people and they usually don’t cause any problems, but they make toxins that in rare cases can enter in our blood stream which leads to Toxic shock syndrome. The underlying mechanisms involves the production of super antigens during invasive streptococcus infection or a localized staphylococcus infection. In both TSS and TSLS, disease progression stems from a super antigen Toxin 1 from staphylococcus aureus or TSST-1 secreted as single polypeptide chain. The gene encoding toxic shock syndrome toxin is carried by a mobile genetic element of S. aureus and the SAPi family of pathogenicity islands. The toxin causes the non-specific binding of MHC II, on professional antigen presenting cell, with T-cell receptors, on T cells. In typical T-cell recognition, an antigen is taken up by an antigen-presenting cell, processed, expressed on the cell surface in complex with class II major histocompatibility complex in a groove formed by the alpha and beta chains of class II MHC, and recognized by an antigen-specific T-cell receptor. This results in polyclonal T-cell activation. Super antigens do not require processing by antigen-presenting cells but instead interact directly with invariant region of the class II MHC molecule. In patients with TSS, up to 20% of the body’s T-cells can be activated at one time. This polyclonal T-cell population causes a cytokine strom, followed by multisystem disease. Most cases of toxic shock syndrome occur in menstruating females in association with the use of tampons. It has been associated with the superabsorbent tampons. Toxic shock syndrome can effect anyone child, male and female possible cause can include, high fever, accompanied by low blood pressure. Malaise and confusion, which can rapidly progress to stupor, coma, and multiple organ failure. The severity if the disease often needs hospitalization. Admission to the intensive care unit is often necessary for supportive care (for aggressive fluid management, ventilation, renal replacement therapy and inotropic support), particularly in the case of multiple organ failure.Treatment includes removal or draining of the source of infection often tampon and draining of abscesses. Outcomes are poorer in patients who do not have the source of infection removed. 

Antibiotic treatment should cover both S pyogenes and S aureus. This may include a combination of cephalosporin’s, penicillin’s or vancomycin. The addition of clindamycin or gentamycin reduces oxin production and mortality. 

A significant number of cases of TSS involve tampon use and especially super absorbent tampons. Soft tissues injuries that can also lead to TSS include the complications of childbirth, an injury or burn, a localized infection, such as a boil, or the use of a contraceptive sponge. Tampon use is implicated in 55 percent of cases, but another 15 percent are linked to childbirth and infected wounds. From December 2015 to March 2016, five cases of menstrual-related TSS were reported in Michigan State. Four of the women were using super absorbency tampons. The bacteria that cause TSS are not uncommon. Between 20 percent and 30 percent of all humans carry S. aureus on their skin and nose usually without complications. Most people have antibodies to protect them. It may be that some people do not develop the necessary antibodies. One possibilities are that super absorbent tampons, the ones that stay inside the body for the longest time become breeding grounds for bacteria. Another is that tampon fibers scratch the vagina, making it possible for bacteria to get through and into the bloodstream. Either the action or the composition of the tampons combined with preexisting staphylococcal bacteria in the vagina, probably triggering the disease. 

Preventing toxic shock syndrome

The following things can reduce your risk to toxic shock syndrome 

Treat wounds and burns quickly and get medical advice if your notice signs of an infection, such as swelling, redness and increasing pain

Always use a tampon with the lowest absorbency suitable for your period

Alternate between tampons and a sanitary towel or panty liner during your period 

Wash your hand before and after inserting tampon 

Change tampons regularly- as often as directed on the pack (usually at least every 4 to 8 hours) 

Never have more than one tampon in your vagina at a time 

When using a tampon at night, insert a fresh tampon before going to bed and remove it when you wake up.

Remove a tampon at the end of your period 

When using female barrier contraception, follow the manufacturers instruction about how long you can leave it in 

It’s a good idea to avoid using tampons or female barrier contraception of you has TSS before.

Precaution is always better than a cure.

Prehistoric humans ate bone marrow like canned soup 400,000 years ago

Tel Aviv University researchers, in collaboration with scholars from Spain, have uncovered evidence of the storage and delayed consumption of animal bone marrow at Qesem Cave near Tel Aviv, the site of many major discoveries from the late Lower Paleolithic period some 400,000 years ago.

The research provides direct evidence that early Paleolithic people saved animal bones for up to nine weeks before feasting on them inside Qesem Cave.

The study, which was published in the October 9 issue of Science Advances, was led by Dr. Ruth Blasco of TAU's Department of Archaeology and Ancient Near Eastern Civilizations and Centro Nacional de Investigación Sobre la Evolución Humana (CENIEH) and her TAU colleagues Prof. Ran Barkai and Prof. Avi Gopher. It was conducted in collaboration with Profs. Jordi Rosell and Maite Arilla of Universitat Rovira i Virgili (URV) and Institut Català de Paleoecologia Humana i Evolució Social (IPHES); Prof. Antoni Margalida of University of Lleida, University of Bern, and the Institute for Game and Wildlife Research (IREC); and Prof. Daniel Villalba of University of Lleida.

"Bone marrow constitutes a significant source of nutrition and as such was long featured in the prehistoric diet," explains Prof. Barkai. "Until now, evidence has pointed to immediate consumption of marrow following the procurement and removal of soft tissues. In our paper, we present evidence of storage and delayed consumption of bone marrow at Qesem Cave."

"This is the earliest evidence of such behavior and offers insight into the socioeconomics of the humans who lived at Qesem," adds Dr. Blasco. "It also marks a threshold for new modes of Paleolithic human adaptation."

"Prehistoric humans brought to the cave selected body parts of the hunted animal carcasses," explains Prof. Rosell. "The most common prey was fallow deer, and limbs and skulls were brought to the cave while the rest of the carcass was stripped of meat and fat at the hunting scene and left there. We found that the deer leg bones, specifically the metapodials, exhibited unique chopping marks on the shafts, which are not characteristic of the marks left from stripping fresh skin to fracture the bone and extract the marrow."

The researchers contend that the deer metapodials were kept at the cave covered in skin to facilitate the preservation of marrow for consumption in time of need.

The researchers evaluated the preservation of bone marrow using an experimental series on deer, controlling exposure time and environmental parameters, combined with chemical analyses. The combination of archaeological and experimental results allowed them to isolate the specific marks linked to dry skin removal and determine a low rate of marrow fat degradation of up to nine weeks of exposure.

"We discovered that preserving the bone along with the skin, for a period that could last for many weeks, enabled early humans to break the bone when necessary and eat the still nutritious bone marrow," adds Dr. Blasco.

"The bones were used as 'cans' that preserved the bone marrow for a long period until it was time to take off the dry skin, shatter the bone and eat the marrow," Prof. Barkai emphasizes.

Until recently, it was believed that the Paleolithic people were hunter gatherers who lived hand-to-mouth (the Stone Age version of farm-to-table), consuming whatever they caught that day and enduring long periods of hunger when food sources were scarce.

"We show for the first time in our study that 420,000 to 200,000 years ago, prehistoric humans at Qesem Cave were sophisticated enough, intelligent enough and talented enough to know that it was possible to preserve particular bones of animals under specific conditions, and, when necessary, remove the skin, crack the bone and eat the bone marrow," Prof. Gopher explains.

According to the research, this is the earliest evidence in the world of food preservation and delayed consumption of food. This discovery joins other evidence of innovative behaviors found in Qesem Cave including recycling, the regular use of fire, and cooking and roasting meat.

"We assume that all this was because elephants, previously a major source of food for humans, were no longer available, so the prehistoric humans in our region had to develop and invent new ways of living," concludes Prof. Barkai. "This kind of behavior allowed humans to evolve and enter into a far more sophisticated kind of socioeconomic existence."

Does rheumatoid arthritis lead to depression?

Does rheumatoid arthritis lead to depression?

Rheumatoid arthritis is a chronic illness that affects 1.3 million adults in the USA, it is a systemic inflammatory disease that affects people both physically and mentally. Major depressive disorder is common in patients with RA. It is being suggested that depression in rheumatoid arthritis is nearly three times that of the general population, yet if often goes undiagnosed. One of the reason for this is that some of the symptoms of RA, such as fatigue and poor sleep could easily be attributed to the disease, when they could also be an indicator of poor mood and or anxiety. However, though people with RA are more susceptible to depression than the general population, many RA will not experience this symptom and it is thought it may only affect around 13-20% of RA patients. The coexistence of immune-mediated inflammatory diseases with depression has long been recognized. Data that illustrate the intimidate associations between peripheral and brain immune responses raise the possibility of shared pathophysiological mechanisms. These associations include the negative effects of proinflammatory cytokines on monoaminergic neurotransmission, neurotropic factors, measures of synaptic plasticity. Levels of C reactive protein of the ways researches measure inflammation, are often higher in people with depression. The evidence supporting this association is accumulating and includes findings from clinical trials of immunomodulatory therapy, indicating that these interventions can provide benefits to mental health independent of improvements of physical disease scores.  

In many cases depression has been underdiagnosed. The study in the British journal practice noted that people may think of their depression and anxiety normal. They may also think doctors place more importance on treating the physical symptoms of RA rather than potentially related mental health conditions. Living with untreated Ra and mental illness can make both the diseases worse. According to the mayo clinic, untreated depression can make it harder to treat RA. That’s supported by recent research. 

A 2017 study in the journal Psychosmatic Medicine, found the link between depression and RA goes both ways. Pain from RA can make depression worse, which in turns makes it harder to manage RA symptoms. That is in part because pain causes stress, and the stress causes release of chemicals that changes moods. When mood changes, there is a domino effect. It’s harder to sleep and stress levels may rise. Simply put, anxiety and depression appear to worsen pain or make it more difficult to manage pain. 

Doctors may not do formal evaluations of a patient’s mood state when they are attending clinic, perhaps due to lack of time, resources, training, or a belief that someone else, such as the General Practitioner should take responsibility for these assessments. Unfortunately, undiagnosed depression can mean that patient may find coping with the demands of suggested treatments, and efforts required for effective self-management too hard to make, and a patient may not avail themselves potentially useful medications and interventions. Furthermore, if the symptoms being experienced are actually more to do with the depression than the RA, patients can become disenchanted with the treatments that apparently do not work, as they do not feel better. 

People may not realize that they are depressed, and so do not talk to their doctor about how they feel. Some people also still worry about perceived stigma of admitting to feeling low, and being diagnosed with a mental health condition. The people mentioned at the beginning of this factsheet have spoken out because of this, and are trying to raise the profile of mental health issues both here and internationally. 

Focusing only on RA, without addressing mental health conditions like anxiety depression, can lead to lower quality of life. The mayo clinic states that people may see a decline in various aspects of daily living. They may have higher pain levels and greater risk of heart disease. Personal relationships and productivity of work may also be affected. 

Do high levels of triglycerides increase the risk of heart failure?

Do high levels of triglycerides increase the risk of heart failure?

Triglycerides is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of the body fat in humans and other vertebrates, as well as from vegetable fat. They are also present in the blood in the type of the fat (lipids) found in the blood. When we eat our body converts calories which it doesn’t need to use right awayinto triglycerides for energy between meals. If you regularly eat more calories than you burn, particularly from high carbohydrates food, you may have high triglycerides. What's considered normal?

• A simple blood test can reveal whether your triglycerides fall into a healthy range:
• Normal — Less than 150 milligrams per deciliter (mg/dL), or less than 1.7 millimoles per liter (mmol/L)
• Borderline high — 150 to 199 mg/dL (1.8 to 2.2 mmol/L)
• High — 200 to 499 mg/dL (2.3 to 5.6 mmol)
• Very high — 500 mg/dL or above (5.7 mmol/L or above)

Presence of high triglycerides may contribute to the hardening of the arteries or thickening of the artery walls which increases the risk of stroke, heart attack and heart disease. The American heart association sets the normal threshold for triglycerides at 150 milligrams per deciliter of blood. Some people have genetic disorder that causes their levels to climb above 1000, which puts them at risk for complications like pancreatitis, “ but they don’t seem at the risk for heart disease, “ Dr. Underberg said. 

Triglycerides can also rise as side effects of certain medications, as well as from obesity and increased alcohol consumption. 

Many people with Type 2 diabetes are at a risk of having a syndrome called diabetic dyslipidemia characterized by high triglycerides and a low concentration of protective HDL cholesterol. Levels of LDL, or bad cholesterol, may be normal in these people, but often they have a plethora of small, dense LDL particles that contribute to inflammation and raise heart diseases risk. 

While some studies cite high triglycerides as an independent risk factor for heart disease, others suggest it is hard to separate the impact of triglycerides from other factors. In alarge analysis of studies published in Circulation in 2007, for example, researchers found a strong association between high triglycerides and coronary heart disease. But takinginto account factors like HDL levels weakened the association between triglycerides and cardiovascular risk.

“What I tell my patients is that triglycerides themselves probably don’t cause heart disease,” Dr. Underberg said. “But for many people they can be a marker of increased risk — a warning sign that you need to look for things like small, dense LDL particles, low HDL, hypertension and diabetes.”

Life's building blocks may have formed in interstellar clouds

An experiment shows that one of the basic units of life -- nucleobases -- could have originated within giant gas clouds interspersed between the stars.

Essential building blocks of DNA -- compounds called nucleobases -- have been detected for the first time in a simulated environment mimicking gaseous clouds that are found interspersed between stars. The finding, published in the journal Nature Communications, brings us closer to understanding the origins of life on Earth.

"This result could be key to unravelling fundamental questions for humankind, such as what organic compounds existed during the formation of the solar system and how they contributed to the birth of life on Earth" says Yasuhiro Oba of Hokkaido University's Institute of Low Temperature Science.

Scientists have already detected some of the basic organic molecules necessary for the beginnings of life in comets, asteroids, and in interstellar molecular clouds: giant gaseous clouds dispersed between stars. It is thought that these molecules could have reached Earth through meteorite impacts some four billion years ago, providing key ingredients for the chemical cocktail that gave rise to life. Learning how these molecules formed is vital to understanding the origins of life.

The basic structural unit of DNA and RNA is called a nucleotide and is composed of a nucleobase, a sugar, and a phosphate group. Previous studies mimicking the expected conditions in interstellar molecular clouds have detected the presence of sugar and phosphate, but not of nucleobases.

Now, Yasuhiro Oba and colleagues at Hokkaido University, Kyushu University, and the Japan Agency for Marine-Earth Science and Technology (JAMSTEC) have used advanced analytical methods to detect the fundamental nucleobases in a simulated interstellar cloud environment.

The team conducted their experiments in an ultra-high vacuum reaction chamber. A gaseous mixture of water, carbon monoxide, ammonia, and methanol was continuously supplied onto a cosmic-dust analogue at a temperature of -263° Celsius. Two deuterium discharge lamps attached to the chamber supplied vacuum ultraviolet light to induce chemical reactions. The process led to the formation of an icy film on the dust analogue inside the chamber.

The team used a high-resolution mass spectrometer and a high-performance liquid chromatograph to analyse the product that formed on the substrate after warming it to room temperature. Recent advances in these technological tools allowed them to detect the presence of the nucleobases cytosine, uracil, thymine, adenine, xanthine, and hypoxanthine. They also detected amino acids, which are the building blocks of proteins, and several kinds of dipeptide, or a dimer of amino acid, in the same product.

The team suspects that past experiments simulating interstellar molecular cloud environments would have produced nucleobases, but that the analytical tools used were not sensitive enough to detect them in complex mixtures.

"Our findings suggest that the processes we reproduced could lead to the formation of the molecular precursors of life," says Yasuhiro Oba. "The results could improve our understanding of the early stages of chemical evolution in space."

Brave new world: Simple changes in intensity of weather events 'could be lethal'

Hurricane Dorian is the latest example of a frightening trend. Extreme weather events are becoming more frequent, more severe and more widespread as a consequence of climate change. New research from Washington University in St. Louis provides important new insights into how different species may fare under this new normal.

Faced with unprecedented change, animals and plants are scrambling to catch up -- with mixed results. A new model developed by Carlos Botero, assistant professor of biology in Arts & Sciences, and Thomas Haaland, formerly a graduate student at the Norwegian University of Science and Technology, helps to predict the types of changes that could drive a given species to extinction.

The study, published Sept. 27 in the journal Ecology and Evolution, challenges the idea that species previously exposed to more variable conditions are more likely to survive extreme events.

"It is difficult to predict how organisms will respond to changes in extreme events because these events tend to be, by definition, quite rare," Botero said. "But we can have a pretty good idea of how any given species may respond to current changes in this aspect of climate -- if we pay attention to its natura

history, and have some idea of the climatic regime it has experienced in the past."

Unexpected vulnerabilities

Researchers in the Botero laboratory use a variety of tools from ecology and evolutionary biology to explore how life -- from bacteria to humans -- copes with and adapts to repeated environmental change.

For the new study, Botero worked with his former student Haaland, now a postdoctoral fellow at the University of Zurich in Switzerland, to develop an evolutionary model of how populations respond to rare environmental extremes. (Think: 500-year floods.) These rare events can be tricky for evolution because it is difficult to adapt to hazards that are almost never encountered.

Through computer simulations, Haaland and Botero found that certain traits and experiences emerged as key indicators of vulnerability.

Specifically, they found:

• Species that breed a single time in their lifetime tend to evolve conservative behaviors or morphologies, as if they were expecting to experience an environmental extreme every time.
• In contrast, species in which a single individual can reproduce multiple times and in different contexts (say, a bird that nests several times in a season and in different trees), evolution favors behaving as if environmental extremes simply never happen.

The key insight of this new model is that species belonging to the former, "conservative" category can easily adapt to more frequent or widespread extremes but have trouble adjusting when those extremes become more intense. The opposite is true of species in the latter, "care-free" category.

Haaland and Botero also found that factors speeding up trait evolution are generally likely to hinder -- rather than favor -- adaptation to rare selection events. Part of the reason: High mutation rates tend to facilitate the process of adaptation to normal conditions during the long intervals in between environmental extremes.

"Our results challenge the idea that species that have been historically exposed to more variable environments are better suited to cope with climate change," Botero said.

"We see that simple changes in the pattern and intensity of environmental extremes could be lethal even for populations that have experienced similar events in the past. This model simply helps us better understand when and where we may have a problem."

Applicable to many environmental extremes

The simple framework that Haaland and Botero describe can be applied to any kind of environmental extreme including flooding, wildfires, heatwaves, droughts, cold spells, tornadoes and hurricanes -- any and all of which might be considered part of the "new normal" under climate change.

Take extreme heat as an example. The model can be used to predict what will happen to animal or plant species when there are more heat waves, when heatwaves last longer, or when typical heat waves affect larger areas.

"Regions in which heat waves used to be rare and patchy are likely to host primarily species that do not exhibit conspicuous adaptations to extreme heat," Botero said. "Our model indicates that the biggest threats of extinction in these particular locations will therefore be more frequent or widespread heat waves, and that the species of highest concern in these places will be endemics and species with small geographic distribution.

"Conversely, areas in which heat waves were historically common and widespread can be expected to host species that already exhibit adaptations for extreme heat," Botero added. "In this case, our model suggests that the typical inhabitants of these places are likely to be more vulnerable to hotter temperatures than to longer or more widespread heat waves."

Informing conservation actions

The new model gives wildlife managers and conservation organizations insight into the potential vulnerabilities of different species based on relatively simple assessments of their natural histories and historical environments.

For example, a 2018 study by Colin Donihue, visiting postdoctoral fellow at Washington University, found that Anolis lizards in the Caribbean tend to evolve larger toepads and shorter limb lengths in response to hurricanes because these traits help them cling better to branches during strong winds. The new model suggests that while these lizards are unlikely to be affected by more frequent hurricanes, their populations may nevertheless face a significant threat of extinction if future hurricanes become more intense. A possible solution to this problem might be to provide wind refuges across the island to allow parts of the population escape winds of very high intensity, Botero suggested.

"While this simple conservation action is unlikely to completely shift the balance from a 'conservative' to a 'care-free' evolutionary response to extreme events, it may nevertheless reduce the strongest vulnerability of these 'conservative' lizard populations," Botero said. "It might just buy them enough time to accumulate sufficient evolutionary changes in their toes and limbs to meet the new demands of their altered habitat."

Fruit flies live longer with combination drug treatment

A triple drug combination has been used to extend the lifespan of fruit flies by 48% in a new study led by UCL and the Max Planck Institute for Biology of Ageing.

The three drugs are all already in use as medical treatments: lithium as a mood stabiliser, trametinib as a cancer treatment and rapamycin as an immune system regulator.

The findings, published in Proceedings of the National Academy of Sciences (PNAS), suggest that a combination drug treatment may one day be helpful at preventing age-related diseases in people.

"As life expectancies increase, we are also seeing an increase of age-related diseases so there is an urgent need to find ways to improve health in old age," said the study's co-lead author, Dr Jorge Castillo-Quan, who began the research at the UCL Institute of Healthy Ageing before moving to Joslin Diabetes Center, Harvard Medical School.

"Here, by studying fruit flies which age much more rapidly than people, we have found that a combination drug treatment targeting different cellular processes may be an effective way to slow down the ageing process."

The researchers were building on previous studies finding that lithium, trametinib and rapamycin can each extend lifespan in fruit flies (Drosophila), which is supported by other preliminary evidence in mice, worms, and cells, and observational findings in people.

The three drugs all act on different cellular signalling pathways that together form the nutrient sensing network, which is conserved across evolution from worms and flies all the way to humans. This network adjusts what the body is doing in response to changes in nutrient levels. The three drugs in question act on different proteins of this network to slow the ageing process and delay the onset of age-related death.

For the latest study, the researchers gave fruit flies doses of lithium, trametinib and rapamycin, separately and in combination. Each drug individually extended lifespan by an average of 11%, while pairing two drugs extended lifespan by roughly 30%. When the three drugs were combined, the fruit flies lived 48% longer than flies in a control group that were not given the treatment.

"Previous studies in fruit flies have achieved lifespan extensions of about 5-20%, so we found it was quite remarkable that this drug combination enabled them to live 48% longer," Dr Castillo-Quan said.

The researchers found that in addition to acting on separate signalling pathways within the nutrient sensing network, the drugs also appear to complement each other to reduce side effects. Rapamycin has undesirable effects on fat metabolism, which can be similar to insulin resistance in peoplebut lithium appeared to cancel out this effect when the two drugs were given together.

The researchers will continue their research to better understand exactly how the drugs work in combination with each other, and hope to progress to experiments in more complex animals, such as mice, to gauge the effects on the entire body before eventually progressing to human trials.

Principal investigator, Professor Linda Partridge (UCL Institute of Health Ageing and Max Planck Institute for Biology of Ageing), said: "There is a growing body of evidence that polypills -- pills that combine low doses of multiple pharmaceutical products -- could be effective as a medication to prevent age-related diseases, given the complex nature of the ageing process. This may be possible by combining the drugs we're investigating with other promising drugs, but there is a long way to go before we will be able to roll out effective treatments."

"My research groups are working to understand the mechanism of the ageing process in order to find ways to help people stay healthy for longer. We are not trying to cheat death, but help people be healthy and disease-free in their final years," she said.

The study was funded by the Max Planck Society, American Federation for Aging Research, Glenn Foundation, National Institutes of Health, European Research Council, Research Into Ageing, Parkinson's UK, Wellcome and Academy of Medical Sciences and involved researchers in UCL Genetics, Evolution & Environment, UCL Queen Square Institute of Neurology, UCL Cancer Institute, Max Planck Institute for Biology of Ageing and Harvard University.

Do high levels of triglycerides increase the risk of heart failure?

Do high levels of triglycerides increase the risk of heart failure?

Triglycerides is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of the body fat in humans and other vertebrates, as well as from vegetable fat. They are also present in the blood in the type of the fat (lipids) found in the blood. When we eat our body converts calories which it doesn’t need to use right away into triglycerides for energy between meals. If you regularly eat more calories than you burn, particularly from high carbohydrates food, you may have high triglycerides. What's considered normal?

A simple blood test can reveal whether your triglycerides fall into a healthy range:

• Normal — Less than 150 milligrams per deciliter (mg/dL), or less than 1.7 millimoles per liter (mmol/L)
• Borderline high — 150 to 199 mg/dL (1.8 to 2.2 mmol/L)
• High — 200 to 499 mg/dL (2.3 to 5.6 mmol)
• Very high — 500 mg/dL or above (5.7 mmol/L or above)

Presence of high triglycerides may contribute to the hardening of the arteries or thickening of the artery walls which increases the risk of stroke, heart attack and heart disease. The American heart association sets the normal threshold for triglycerides at 150 milligrams per deciliter of blood. Some people have genetic disorder that causes their levels to climb above 1000, which puts them at risk for complications like pancreatitis, “ but they don’t seem at the risk for heart disease, “ Dr. Underberg said. 

Triglycerides can also rise as side effects of certain medications, as well as from obesity and increased alcohol consumption. 

Many people with Type 2 diabetes are at a risk of having a syndrome called diabetic dyslipidemia characterized by high triglycerides and a low concentration of protective HDL cholesterol. Levels of LDL, or bad cholesterol, may be normal in these people, but often they have a plethora of small, dense LDL particles that contribute to inflammation and raise heart diseases risk. 

While some studies cite high triglycerides as an independent risk factor for heart disease, others suggest it is hard to separate the impact of triglycerides from other factors. In a arge analysis of studies published in Circulation in 2007, for example, researchers found a strong association between high triglycerides and coronary heart disease. But taking into account factors like HDL levels weakened the association between triglycerides and cardiovascular risk.

“What I tell my patients is that triglycerides themselves probably don’t cause heart disease,” Dr. Underberg said. “But for many people they can be a marker of increased risk — a warning sign that you need to look for things like small, dense LDL particles, low HDL, hypertension and diabetes.”