Sette giorni senza sonno, 700 geni alterati

Dormire poco per sette giorni di fila, o peggio non dormire affatto, non solo nuoce genericamente alla salute, alterando livelli di attenzione, senso di fame, livelli di stress, come molti studi hanno dimostrato.
Ma secondo l’ultima ricerca scientifica inglese, lo scarso sonno modifica anche il funzionamento dei nostri geni.
Sarebbero oltre 700 quelli del nostro Dna che, dopo un periodo di riposo mancante, verrebbero interessati.
Questo nonostante molti studiosi abbiano, negli ultimi mesi, dimostrato come comunque sia il nostro fisico a riequilibrare i ritmi di sonno e veglia nel tempo, e dopo alcuni giorni di sonno mancante il corpo umano si riprenda da sé le ore perdute.

IL SONNO MANCATO – Lo studio inglese – pubblicato su Pnas - è stato condotto dai ricercatori dell’università del Surrey sugli «effetti della mancanza di sonno nei ritmi circadiani e sue ricadute sul trascrittoma», ovvero il genoma umano, usando una base di 26 volontari in buona salute, che per una settimana sono stati tenuti sotto controllo in un centro inglese che cura i disturbi del sonno.
Il campione è stato privato per sette giorni di alcune ore di sonno e obbligato a dormire 6 ore per notte.
A fine periodo, per compiere le analisi sul Dna le stesse cavie sono state tenute sveglie per 40 ore di fila.
Accanto a loro, un gruppo di persone (il cosiddetto gruppo di controllo) ha invece riposato fino a 10 ore per notte.
Le analisi della loro composizione genetica sono poi state paragonate dai ricercatori del Surrey, che hanno anche monitorato le abilità cognitive del campione e la qualità del loro sonno.

QUEI GENI IMPAZZITI – Dai dati raccolti, è emerso come nel caso di 711 geni sia variata la loro capacità di lavoro: in alcuni casi questa veniva intensificata, in altri decelerava. Tra questi, le attività che cambiavano maggiormente riguardavano i geni responsabili della regolazione del metabolismo, dei livelli di stress e della risposta del corpo a tali sollecitazioni, dell’omeostasi, ovvero dell’equilibrio interno del nostro corpo, termometro fondamentale per mantenere un corretto stato di salute.
Tali modifiche dunque, potrebbero influire sulle condizioni fisiche del corpo umano, se messe costantemente alla prova.
Ecco perché chi cronicamente dorme poco si troverebbe in un’area considerata a rischio. Questa scoperta peraltro dà finalmente una motivazione anche genetica alle conseguenze dello scarso sonno da sempre predicate e verificate da parte dei medici: tendenza a mangiare di più, a non digerire, a ingrassare per esempio, ma anche minor capacità di gestione dello stress, e un generico e vario affaticamento fisico e mentale.
Non a caso, lo stesso campione analizzato ha mostrato capacità cognitive più basse della media nei giorni di deprivazione dal sonno, rispondendo con lentezza e fatica ai test di attenzione e memoria.

Unchecked Antibiotic Use in Animals May Affect Global Human Health

From Science Daily website (see original article).


Feb. 11, 2013 — The increasing production and use of antibiotics, about half of which is used in animal production, is mirrored by the growing number of antibiotic resistance genes, or ARGs, effectively reducing antibiotics' ability to fend off diseases -- in animals and humans.

A study in the current issue of the Proceedings of the National Academy of Sciences shows that China -- the world's largest producer and consumer of antibiotics -- and many other countries don't monitor the powerful medicine's usage or impact on the environment.

On Chinese commercial pig farms, researchers found 149 unique ARGs, some at levels 192 to 28,000 times higher than the control samples, said James Tiedje, Michigan State University Distinguished Professor of microbiology and molecular genetics and of plant, soil and microbial sciences, and one of the co-authors.

"Our research took place in China, but it reflects what's happening in many places around the world," said Tiedje, part of the research team led by Yong-Guan Zhu of the Chinese Academy of Sciences.
"The World Organization for Animal Health and the U.S. Food and Drug Administration have been advocating for improved regulation of veterinary antibiotic use because those genes don't stay local."

Antibiotics in China are weakly regulated, and the country uses four times more antibiotics for veterinary use than in the United States.
Since the medicine is poorly absorbed by animals, much of it ends up in manure -- an estimated 700 million tons annually from China alone.
This is traditionally spread as fertilizer, sold as compost or ends up downstream in rivers or groundwater, taking ARGs with them.
Along with hitching rides in fertilizer, ARGs also are spread via international trade, immigration and recreational travel.

Daily exposure to antibiotics, such as those in animal feed, allows microbes carrying ARGs to thrive.
In some cases, these antibiotic resistant genes become highly mobile, meaning they can be transferred to other bacteria that can cause illness in humans.
This is a big concern because the infections they cause can't be treated with antibiotics.

ARGs can reach the general population through food crops, drinking water and interactions with farm workers.
Because of this undesirable cycle, ARGs pose a potential global risk to human health and should be classified as pollutants, said Tiedje, an MSU AgBioResearch scientist.

"It is urgent that we protect the effectiveness of our current antibiotics because discovering new ones is extremely difficult," Zhu said.
"Multidrug resistance is a global problem and must be addressed in a comprehensive manner, and one area that needs to be addressed is more judicious use and management of wastes that contain ARGs.

Vitamin D, Omega-3 May Help Clear Amyloid Plaques Found in Alzheimer's

From Science Daily website (see original article).

Feb. 5, 2013 — A team of academic researchers has pinpointed how vitamin D3 and omega-3 fatty acids may enhance the immune system's ability to clear the brain of amyloid plaques, one of the hallmarks of Alzheimer's disease.

In a small pilot study published in the Feb. 5 issue of the Journal of Alzheimer's Disease, the scientists identified key genes and signaling networks regulated by vitamin D3 and the omega-3 fatty acid DHA (docosahexaenoic acid) that may help control inflammation and improve plaque clearance.

Previous laboratory work by the team helped clarify key mechanisms involved in helping vitamin D3 clear amyloid-beta, the abnormal protein found in the plaque.
The new study extends the previous findings with vitamin D3 and highlights the role of omega-3 DHA.

"Our new study sheds further light on a possible role for nutritional substances such as vitamin D3 and omega-3 in boosting immunity to help fight Alzheimer's," said study author Dr. Milan Fiala, a researcher at the David Geffen School of Medicine at UCLA.

For the study, scientists drew blood samples from both Alzheimer's patients and healthy controls, then isolated critical immune cells called macrophages from the blood. Macrophages are responsible for gobbling up amyloid-beta and other waste products in the brain and body.

The team incubated the immune cells overnight with amyloid-beta. They added either an active form of vitamin D3 called 1alpha,25–dihydroxyvitamin D3 or an active form of the omega-3 fatty acid DHA called resolvin D1 to some of the cells to gauge the effect they had on inflammation and amyloid-beta absorption.

Both 1alpha, 25-dihydroxyvitamin D3 and resolvin D1 improved the ability of the Alzheimer's disease patients' macrophages to gobble-up amyloid-beta, and they inhibited the cell death that is induced by amyloid-beta.
Researchers observed that each nutrition molecule utilized different receptors and common signaling pathways to do this.

Previous work by the team, based on the function of Alzheimer's patients' macrophages, showed that there are two groups of patients and macrophages.
In the current study, researchers found that the macrophages of the Alzheimer's patients differentially expressed inflammatory genes, compared with the healthy controls, and that two distinct transcription patterns were found that further define the two groups: Group 1 had an increased transcription of inflammatory genes, while Group 2 had decreased transcription. Transcription is the first step leading to gene expression.

"Further study may help us identify if these two distinct transcription patterns of inflammatory genes could possibly distinguish either two stages or two types of Alzheimer's disease," said study author Mathew Mizwicki, an assistant researcher at the David Geffen School of Medicine at UCLA.

While researchers found that 1alpha,25-dihydroxyvitamin D3 and resolvin D1 greatly improved the clearance of amyloid-beta by macrophages in patients in both groups, they discovered subtleties in the effects the two substances had on the expression of inflammatory genes in the two groups.
In Group 1, the increased-inflammation group, macrophages showed a decrease of inflammatory activation; in Group 2, macrophages showed an increase of the inflammatory genes IL1 and TLRs when either 1alpha,25-Dihydroxyvitamin D3 or resolvin D1 were added.

More study is needed, Fiala said, but these differences could be associated with the severity of patients' nutritional and/or metabolic deficiencies of vitamin D3 and DHA, as well as the omega-3 fatty acid EPA (eicosapentaenoic acid).

"We may find that we need to carefully balance the supplementation with vitamin D3 and omega-3 fatty acids, depending on each patient in order to help promote efficient clearing of amyloid-beta," Fiala said.
"This is a first step in understanding what form and in which patients these nutrition substances might work best."

According to Fiala, an active (not oxidized) form of omega-3 DHA, which is the precursor of the resolvin D1 used in this study, may work better than more commercially available forms of DHA, which generally are not protected against the oxidation that can render a molecule inactive.

The next step is a larger study to help confirm the findings, as well as a clinical trial with omega-3 DHA, the researchers said.

The Alzheimer's Association contributed to the initial phase of the study.
Fiala is a consultant for the Smartfish Company that is producing a drink with an active form of omega-3 DHA.

Zinc Helps Against Infection by Tapping Brakes in Immune Response

From Science Daily website (see original article).

Feb. 7, 2013 — New research suggests that zinc helps control infections by gently tapping the brakes on the immune response in a way that prevents out-of-control inflammation that can be damaging and even deadly.

Scientists determined in human cell culture and animal studies that a protein lures zinc into key cells that are first-responders against infection. The zinc then interacts with a process that is vital to the fight against infection and by doing so helps balance the immune response.

This study revealed for the first time that zinc homes in on this pathway and helps shut it down, effectively ensuring that the immune response does not spiral out of control. The team led by Ohio State University researchers also found that if there is not enough zinc available at the time of infection, the consequences include excessive inflammation.

In this research, zinc's activity was studied in the context of sepsis, a devastating systemic response to infection that is a common cause of death in intensive-care unit patients. But scientists say these findings might also help explain why taking zinc tablets at the start of a common cold appears to help stem the effects of the illness.

"We do believe that to some extent, these findings are going to be applicable to other important areas of disease beyond sepsis," said Daren Knoell, senior author of the study and a professor of pharmacy and internal medicine at Ohio State. "Without zinc on board to begin with, it could increase vulnerability to infection. But our work is focused on what happens once you get an infection -- if you are deficient in zinc you are at a disadvantage because your defense system is amplified, and inappropriately so.

"The benefit to health is explicit: Zinc is beneficial because it stops the action of a protein, ultimately preventing excess inflammation."

While this study and previous work linking zinc deficiency to inflammation might suggest that supplementation could help very sick ICU patients, it's still too early to make that leap.

"I think the question is whom to give zinc to, if anybody at all. We predict that not everybody in the ICU with sepsis needs zinc, but I anticipate that a proportion of them would," Knoell said. "Zinc is a critical element that we get from our diet, but we do not think we can give zinc and fix everything. Usually, if there is zinc deficiency, we would expect to see other nutrient deficiencies, too."

Zinc deficiency affects about 2 billion people worldwide, including an estimated 40 percent of the elderly in the United States -- who are also among the most likely Americans to end up in an ICU.

The research is published in the journal Cell Reports.

Knoell's lab previously showed that zinc-deficient mice developed overwhelming inflammation in response to sepsis compared to mice on a normal diet. Zinc supplementation improved outcomes in the zinc-deficient mice.

Until now, the beneficial effects of zinc in combating infection have not been fully understood at the molecular level. This is because zinc has numerous complex jobs in the body and interacts with thousands of proteins to sustain human life. Of all the zinc contained in our bodies, only about 10 percent of it is readily accessible to help fight off an infection, said Knoell, also an investigator in Ohio State's Davis Heart and Lung Research Institute.

"We believe that our findings help to narrow an important gap that has existed in our understanding of how this relatively simple metal helps us defend ourselves from infection," he said.

In this work, Knoell and colleagues sought to zero in on zinc's role in preventing the inflammation that had led to such poor outcomes in the zinc-deficient mice.

In experiments using human monocytes -- cells involved in the first line of defense against an invading pathogen -- the researchers examined what happens when the immune response is launched.

When a pathogen is recognized, a series of molecules wake up from dormancy to create a process that activates the innate immune response. A major part of this process involves the NF-κB pathway, named for a highly active protein that is known to play an important role in the immune response to infection. Once NF-κB is activated and enters the nucleus, a gene is expressed that produces a zinc transporter called ZIP8. The transporter then rapidly mobilizes to the cell's wall, where it can then shuttle zinc from the bloodstream into the cell.

After cell entry, zinc is then directed to and binds to a different protein in the NF-κB pathway. When this happens, it halts any further activity in that process. The cumulative impact of this feedback loop is that it prevents excessive inflammation, which can be damaging to cells and the body.

"The immune system has to work under very strict balance, and this is a classic example of where more is not always better," Knoell said. "We want a robust inflammatory response, which is part of our natural programming to defend us against a bug. But if that is unchecked, and there is too much inflammation, then it not only attacks the pathogen but can also cause much more collateral damage."

The researchers knew from previously published experiments that if ZIP8 activation was prevented, zinc couldn't come into the cell and the cells died. In the current study, collaborators who specialize in computational modeling of protein interactions helped identify the likely target of zinc once it enters the cell: specific binding sites on a protein called IKKB. When researchers allowed this protein to function unchecked in mice with zinc deficiency, the animals developed excessive inflammation in response to sepsis -- confirmation that IKKB was zinc's target to turn off the inflammatory pathway.

"There are certainly other zinc targets in the cell, but we found evidence that zinc is brought in by ZIP8 to turn the pathway off by interacting with this protein at a specific region," Knoell said.

The recommended daily allowance for zinc ranges from 8 to 11 milligrams for most adults. Red meat and poultry provide the majority of zinc in the American diet, according to the National Institutes of Health. Other food sources include beans, nuts, some shellfish, whole grains, fortified cereals and dairy products. The nutrient is also available in supplement form. Knoell said it is possible but relatively uncommon to take in too much zinc to reach toxic levels.

His lab is continuing to study the NF-κB pathway, inflammation and zinc deficiency in other disease processes. And though zinc would be inexpensive and easy to take as a supplement, Knoell said many questions remain about whether zinc should be considered as an intervention for specific disorders.

"There might be therapeutic implications about giving supplemental zinc in a strategic manner to help improve some people with certain conditions. But also, could we learn from this so someday we can be more diagnostic about who it is that needs zinc? And if so, what dose and for how long?" he said.

This work was supported by the National Institutes of Health and the Lifeline of Ohio Tissue Procurement Agency.

Co-authors include Ming-Jie Liu, Shengying Bao, Charlie Pyle, Andrew Rudawsky and Mark Wewers of the Davis Heart and Lung Research Institute; Marina Gálvez-Peralta and Daniel Nebert of the University of Cincinnati Medical Center; Ryan Pavlovicz and Chenglong Li of Ohio State's Biophysics Program (Li is also in the College of Pharmacy); and David Killilea of Children's Hospital Oakland Research Institute.

Green Tea and Red Wine Extracts Interrupt Alzheimer's Disease Pathway in Cells

From Science Daily website (see original article).

Feb. 5, 2013 — Natural chemicals found in green tea and red wine may disrupt a key step of the Alzheimer's disease pathway, according to new research from the University of Leeds.

In early-stage laboratory experiments, the researchers identified the process which allows harmful clumps of protein to latch on to brain cells, causing them to die.
They were able to interrupt this pathway using the purified extracts of EGCG from green tea and resveratrol from red wine.

The findings, published in the Journal of Biological Chemistry, offer potential new targets for developing drugs to treat Alzheimer's disease, which affects some 800,000 people in the UK alone, and for which there is currently no cure.

"This is an important step in increasing our understanding of the cause and progression of Alzheimer's disease," says lead researcher Professor Nigel Hooper of the University's Faculty of Biological Sciences.
"It's a misconception that Alzheimer's is a natural part of aging; it's a disease that we believe can ultimately be cured through finding new opportunities for drug targets like this."

Alzheimer's disease is characterised by a distinct build-up of amyloid protein in the brain, which clumps together to form toxic, sticky balls of varying shapes.
These amyloid balls latch on to the surface of nerve cells in the brain by attaching to proteins on the cell surface called prions, causing the nerve cells to malfunction and eventually die.

"We wanted to investigate whether the precise shape of the amyloid balls is essential for them to attach to the prion receptors, like the way a baseball fits snugly into its glove," says co-author Dr Jo Rushworth.
"And if so, we wanted to see if we could prevent the amyloid balls binding to prion by altering their shape, as this would stop the cells from dying."

The team formed amyloid balls in a test tube and added them to human and animal brain cells.
Professor Hooper said: "When we added the extracts from red wine and green tea, which recent research has shown to re-shape amyloid proteins, the amyloid balls no longer harmed the nerve cells.
We saw that this was because their shape was distorted, so they could no longer bind to prion and disrupt cell function.

"We also showed, for the first time, that when amyloid balls stick to prion, it triggers the production of even more amyloid, in a deadly vicious cycle," he added.

Professor Hooper says that the team's next steps are to understand exactly how the amyloid-prion interaction kills off neurons.

"I'm certain that this will increase our understanding of Alzheimer's disease even further, with the potential to reveal yet more drug targets," he said.

Dr Simon Ridley, Head of Research at Alzheimer's Research UK, the UK's leading dementia research charity, which part-funded the study, said: "Understanding the causes of Alzheimer's is vital if we are to find a way of stopping the disease in its tracks.
While these early-stage results should not be a signal for people to stock up on green tea and red wine, they could provide an important new lead in the search for new and effective treatments.
With half a million people affected by Alzheimer's in the UK, we urgently need treatments that can halt the disease -- that means it's crucial to invest in research to take results like these from the lab bench to the clinic."

Excess Sugar Linked to Cancer

From Science Daily website (see original article).

Feb. 1, 2013 — Sugars are needed to provide us with energy and in moderate amounts contribute to our well-being. Sustained high levels of sugars, as is found in diabetics, damages our cells and now is shown that can also increase our chance to get cancer: "The dose makes the poison" as Paracelsus said.

It is well known that obesity is a leading cause of diabetes, a disease where the body fails to control blood sugar levels.
High blood sugar levels are characteristic in obesity and diabetes.
What is less well known is that diabetes and obesity are also linked to an increase in cancer risk.
That is, the diabetic population has up to double chances to suffer pancreatic or colon cancer among others, according to well sustained epidemiological studies.
With obesity in British and Spanish children reaching 16%, the highest in Europe, this epidemic has major health implications.
How obesity or diabetes increase cancer risk has been a major health issue.

Scientists led by Dr. Custodia Garcia-Jimenez at the University Rey Juan Carlos in Madrid have uncovered a key mechanism that links obesity and diabetes with cancer: high sugar levels, which increase activity of a gene widely implicated in cancer progression.

Dr Garcia Jimenez's laboratory was studying how cells in the intestine respond to sugars and signal to the pancreas to release insulin, the key hormone that controls blood sugar levels.
Sugars in the intestine trigger cells to release a hormone called GIP that enhances insulin release by the pancreas.

In a study published in Molecular Cell, Dr Garcia Jimenez's team showed that the ability of the intestinal cells to secrete GIP is controlled by a protein called β-catenin, and that the activity of β-catenin is strictly dependent on sugar levels.

Increased activity of β-catenin is known to be a major factor in the development of many cancers and can make normal cells immortal, a key step in early stages of cancer progression.
The study demonstrates that high (but not normal) sugar levels induce nuclear accumulation of β-catenin and leads to cell proliferation.
The changes induced on β-catenin, the molecules involved and the diversity of cancer cells susceptible to these changes are identified.

Dr. Custodia García said "We were surprised to realize that changes in our metabolism caused by dietary sugar impact on our cancer risk.
We are now investigating what other dietary components may influence our cancer risk. Changing diet is one of easiest prevention strategies that can potentially save a lot of suffering and money."

Colin Goding, Professor of Oncology at the University of Oxford, UK said 'Previously we were unsure about how increased blood sugar found in diabetes and obesity could increase cancer risk.
This study identifies a key molecular mechanism through which high blood glucose would predispose to cancer.
It opens the way for potential novel therapies aimed at reducing cancer risk in the obese and diabetic populations.'

Estimations published by the World Health Organisation (WHO): Obesity predisposes to diabetes and its prevalence is doubling every 20 years worldwide.
More than 1 in 10 adults worldwide (12%) are obese (BMI>30).
1 in 6 children in UK and Spain suffer obesity.

Diabetes caused 4.6 million deaths in 2011, more than 2 deaths per hour in Spain, more in USA. Worldwide, 1 in 10 adults (10%) suffered from diabetes in 2010 and more than one-third of individuals with diabetes are unaware they suffer from the disease.
The national cost of diabetes or cancer is in the order of billions of pounds or euros in Spain or England.

More than half (63%) of premature deaths worldwide are due to non communicable diseases (NCD) of which cancer and diabetes are among the 4 causes more frequent.
At least 1 in 3 of the main cancers (27-39%) can be prevented by improving diet, physical activity and body composition.

Eating Deep-Fried Food Linked to Increased Risk of Prostate Cancer

From Science Daily website (see original article).

Jan. 28, 2013 — Regular consumption of deep-fried foods such as French fries, fried chicken and doughnuts is associated with an increased risk of prostate cancer, and the effect appears to be slightly stronger with regard to more aggressive forms of the disease, according to a study by investigators at Fred Hutchinson Cancer Research Center.

Corresponding author Janet L. Stanford, Ph.D., and colleagues Marni Stott-Miller, Ph.D., a postdoctoral research fellow and Marian Neuhouser, Ph.D., all of the Hutchinson Center's Public Health Sciences Division, have published their findings online in The Prostate.
While previous studies have suggested that eating foods made with high-heat cooking methods, such as grilled meats, may increase the risk of prostate cancer, this is the first study to examine the addition of deep frying to the equation.

From French fries to doughnuts: Eating more than once a week may raise risk.
Specifically, Stanford, co-director of the Hutchinson Center's Program in Prostate Cancer Research, and colleagues found that men who reported eating French fries, fried chicken, fried fish and/or doughnuts at least once a week were at an increased risk of prostate cancer as compared to men who said they ate such foods less than once a month.

In particular, men who ate one or more of these foods at least weekly had an increased risk of prostate cancer that ranged from 30 to 37 percent.
Weekly consumption of these foods was associated also with a slightly greater risk of more aggressive prostate cancer.
The researchers controlled for factors such as age, race, family history of prostate cancer, body-mass index and PSA screening history when calculating the association between eating deep-fried foods and prostate cancer risk.

"The link between prostate cancer and select deep-fried foods appeared to be limited to the highest level of consumption -- defined in our study as more than once a week -- which suggests that regular consumption of deep-fried foods confers particular risk for developing prostate cancer," Stanford said.

Deep frying may trigger formation of carcinogens in food.
Possible mechanisms behind the increased cancer risk, Stanford hypothesizes, include the fact that when oil is heated to temperatures suitable for deep frying, potentially carcinogenic compounds can form in the fried food.
They include acrylamide (found in carbohydrate-rich foods such as French fries), heterocyclic amines and polycyclic aromatic hydrocarbons (chemicals formed when meat is cooked at high temperatures), aldehyde (an organic compound found in perfume) and acrolein (a chemical found in herbicides).
These toxic compounds are increased with re-use of oil and increased length of frying time.
Foods cooked with high heat also contain high levels of advanced glycation endproducts, or AGEs, which have been associated with chronic inflammation and oxidative stress.
Deep-fried foods are among the highest in AGE content.
A chicken breast deep fried for 20 minutes contains more than nine times the amount of AGEs as a chicken breast boiled for an hour, for example.

For the study, Stanford and colleagues analyzed data from two prior population-based case-control studies involving a total of 1,549 men diagnosed with prostate cancer and 1,492 age-matched healthy controls.
The men were Caucasian and African-American Seattle-area residents and ranged in age from 35 to 74 years.
Participants were asked to fill out a dietary questionnaire about their usual food intake, including specific deep-fried foods.

The first study of its kind "To the best of our knowledge, this is the first study to look at the association between intake of deep-fried food and risk of prostate cancer," Stanford said.
However, deep-fried foods have previously been linked to cancers of the breast, lung, pancreas, head and neck, and esophagus.

Because deep-fried foods are primarily eaten outside the home, it is possible that the link between these foods and prostate cancer risk may be a sign of high consumption of fast foods in general, the authors wrote, citing the dramatic increase in fast-food restaurants and fast-food consumption in the U.S. in the past several decades.

Loneliness, Like Chronic Stress, Taxes the Immune System, Researchers Find

From Science Daily website (see original article).

Jan. 19, 2013 — New research links loneliness to a number of dysfunctional immune responses, suggesting that being lonely has the potential to harm overall health.

Researchers found that people who were more lonely showed signs of elevated latent herpes virus reactivation and produced more inflammation-related proteins in response to acute stress than did people who felt more socially connected.

These proteins signal the presence of inflammation, and chronic inflammation is linked to numerous conditions, including coronary heart disease, Type 2 diabetes, arthritis and Alzheimer's disease, as well as the frailty and functional decline that can accompany aging.

Reactivation of a latent herpes virus is known to be associated with stress, suggesting that loneliness functions as a chronic stressor that triggers a poorly controlled immune response.

"It is clear from previous research that poor-quality relationships are linked to a number of health problems, including premature mortality and all sorts of other very serious health conditions.
And people who are lonely clearly feel like they are in poor-quality relationships," said Lisa Jaremka, a postdoctoral fellow at the Institute for Behavioral Medicine Research at Ohio State University and lead author of the research.

"One reason this type of research is important is to understand how loneliness and relationships broadly affect health.
The more we understand about the process, the more potential there is to counter those negative effects -- to perhaps intervene.
If we don't know the physiological processes, what are we going to do to change them?"

The results are based on a series of studies conducted with two populations: a healthy group of overweight middle-aged adults and a group of breast cancer survivors.
The researchers measured loneliness in all studies using the UCLA Loneliness Scale, a questionnaire that assesses perceptions of social isolation and loneliness.

Jaremka will present the research January 19 at the Society for Personality and Social Psychology annual meeting in New Orleans.

The researchers first sought to obtain a snapshot of immune system behavior related to loneliness by gauging levels of antibodies in the blood that are produced when herpes viruses are reactivated.

Participants were 200 breast cancer survivors who were between two months and three years past completion of cancer treatment with an average age of 51 years.
Their blood was analyzed for the presence of antibodies against Epstein-Barr virus and cytomegalovirus.

Both are herpes viruses that infect a majority of Americans.
About half of infections do not produce illness, but once a person is infected, the viruses remain dormant in the body and can be reactivated, resulting in elevated antibody levels, or titers -- again, often producing no symptoms but hinting at regulatory problems in the cellular immune system.

Lonelier participants had higher levels of antibodies against cytomegalovirus than did less lonely participants, and those higher antibody levels were related to more pain, depression and fatigue symptoms.
No difference was seen in Epstein-Barr virus antibody levels, possibly because this reactivation is linked to age and many of these participants were somewhat older, meaning reactivation related to loneliness would be difficult to detect, Jaremka said.

Previous research has suggested that stress can promote reactivation of these viruses, also resulting in elevated antibody titers.

"The same processes involved in stress and reactivation of these viruses is probably also relevant to the loneliness findings," Jaremka said. "Loneliness has been thought of in many ways as a chronic stressor -- a socially painful situation that can last for quite a long time."

In an additional set of studies, the scientists sought to determine how loneliness affected the production of proinflammatory proteins, or cytokines, in response to stress.
These studies were conducted with 144 women from the same group of breast cancer survivors and a group of 134 overweight middle-aged and older adults with no major health problems.

Baseline blood samples were taken from all participants, who were then subjected to stress -- they were asked to deliver an impromptu five-minute speech and perform a mental arithmetic task in front of a video camera and three panelists.
Researchers followed by stimulating the participants' immune systems with lipopolysaccharide, a compound found on bacterial cell walls that is known to trigger an immune response.

In both populations, those who were lonelier produced significantly higher levels of a cytokine called interleukin-6, or IL-6, in response to acute stress than did participants who were more socially connected.
Levels of another cytokine, tumor necrosis factor-alpha, also rose more dramatically in lonelier participants than in less lonely participants, but the findings were significant by statistical standards in only one study group, the healthy adults.

In the study with breast cancer survivors, researchers also tested for levels of the cytokine interleukin 1-beta, which was produced at higher levels in lonelier participants.

When the scientists controlled for a number of factors, including sleep quality, age and general health measures, the results were the same.

"We saw consistency in the sense that more lonely people in both studies had more inflammation than less lonely people," Jaremka said.

"It's also important to remember the flip side, which is that people who feel very socially connected are experiencing more positive outcomes," she said.