Study results also pave the way for new potential therapeutic targets to rejuvenate the immune system in older adults and thereby reduce their risk of infectious disease.

“Through this study, we have gained a new understanding of why older adults are more susceptible to infectious diseases, which will enable us to identify potential new treatments,” said senior author Michael Demetriou, MD, PhD, a professor of neurology at the UCI School of Medicine and chief of the Division of Multiple Sclerosis and Neuroimmunology at UCI. First author and assistant professor in the UCI Department of Pathology, Haik Mkhikian, MD, PhD, added, “We’ve identified a potential fountain of youth for the immune system.”

The study, titled, “Age-associated impairment of T cell immunity is linked to sex-dimorphic elevation of N-glycan branching,” was published in Nature Aging.

T cell immunity declines with aging, thereby increasing severity and mortality from infectious disease. T cells are the quarterback of the immune system and coordinate immune responses to fight off infections. The addition of complex and branched carbohydrate chains (‘glycans’) to proteins suppresses T cells function.

In this study, researchers show that the branched glycans increase with age in T cells from females more than in males due to age-associated increases in an important sugar metabolite (N-acetylglucosamine) and signaling by the T cell cytokine interleukin-7.

“Our research reveals that reversing the elevation in branched glycans rejuvenates human and mouse T cell function and reduces severity of Salmonella infection in old female mice,” said Demetriou.

Mkhikian added, “This suggests several potential novel therapeutic targets to revitalize old T cells, such as altering branched glycans or the age-triggered elevation in serum N-acetylglucosamine and IL-7 signaling.”

Aging-associated immune dysfunction, referred to as immunosenescence, contributes to increased morbidity and mortality from both infectious and neoplastic diseases in adults aged 65 years and older. In the U.S, for example, around 89 percent of annual deaths from influenza are in people at least 65?years old, despite this age group representing only around 15 percent of the nation’s population. More recently, the vulnerability of older adults to viral infections has been tragically highlighted by the recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Increased morbidity and mortality in older adults also occurs with common bacterial infections such as those caused by the enteric pathogen Salmonella. Furthermore, efficacy of immunizations declines with age, further increasing risk of infection in older adults. The rapidly aging population in the developed world exacerbates this issue and heightens the need for interventions that effectively target immunosenescence.

Previous studies examined transcriptome changes in highly purified aged T cell subsets. In this study, researchers analyzed T cell populations by age and sex, with results suggesting sex-specific differences that imply that effective interventions to reverse immune dysfunction in older adults may require sex-specific strategies.

The study was supported by funding from the National Institute of Allergy and Infectious Disease, the National Center for Complementary and Integrative health, The Burroughs Wellcome Fund and a predoctoral fellowship from the American heart Association.

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Warming winters may sound like a welcome change for some farmers because the change in temperature could reduce freezing stress on plants and create more ideal conditions for growing overwinter cash crops and winter cover crops. However, when looking at climate change from a cross-seasonal perspective and accounting for declining snowpack, researchers are finding that the whole picture isn’t so sunny.

Reduced snow may result in more exposure of winter crops to freeze and could mean greater risks for agricultural drought.

In a new study published in Nature Climate Change, Zhenong Jin, Ph.D., an assistant professor in the Department of Bioproducts and Biosystems Engineering at the University of Minnesota, led an international team in researching the implications that could be associated with warmer winters and declining snowpack, using winter wheat (the largest winter crop in the U.S.) as an example.

“Although the implications of changes in snow for agricultural irrigation are beginning to be understood, the consequences of such for predominantly rainfed winter crops such as winter wheat remain largely unknown. There might be risks for being overoptimistic about growing overwinter crops under climate change,” said Jin.

Researchers used panel regression, a powerful statistical method to analyze repeated observations over time, to attribute the interannual variability of winter wheat yield to multiple interactive environmental factors. These factors included cold season freezing degree days, growing degree days, rainfall and snowfall during the growing season and snow cover fraction during frozen days.

The researchers found:

• From 1999-2019, snow cover insulation weakened yield losses due to freezing stress by 22%.
• Projections show that future reduced snow cover could offset up to one-third of the yield benefit from reduced frost.

“Our study highlighted the potential freezing risk in winters with decreased snow cover, especially when seedlings were exposed to comparatively warmer conditions that caused loss of winter-hardiness, which can cause significant yield losses of winter crops,” said Peng Zhu, Ph.D., a Researcher from the Climate and Environment Sciences Laboratory of the Pierre Simon Laplace Institute, who co-led this study.

This research will help inform breeders as they consider the complex tradeoffs among warming, reduced snowpack and occasional freezing threats when developing climate-smart cultivars.

These results also highlight the necessity of improving the representation of snow associated processes in crop models to better evaluate climate change effects and adaptation potential in cropping systems.

“It is worth noting that in some cropping systems freezing stress is appreciated, since it helps farmers control pests and diseases and snow is even removed or at least made more compact by farmers to increase the freezing of the soil,” said Jin. “When data becomes available, future studies might also need to account for the influence of snow on pests and diseases to comprehensively understand what future changes in snowpack mean for the cropping system.”

Funding for this research was partially supported by the USDA National Institute of Food and Agriculture (NIFA) and the French National Research Agency.

Other members of the University of Minnesota research team include Taegon Kim and Chenxi Lin from Jin’s group and David Mulla from the Department of Soil, Water, and Climate.

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The study was conducted by Professor Frank Hu and colleagues at the Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA, and aimed to identify the metabolite profiles related to different plant-based diets and investigate possible associations between those profiles and the risk of developing T2D.

A metabolite is a substance used or produced by the chemical processes in a living organism and includes the vast number of compounds found in different foods as well as the complex variety of molecules created as those compounds are broken down and transformed for use by the body. Differences in the chemical makeup of foods means that an individual’s diet should be reflected in their metabolite profile. Recent technological advances in the field of high-throughput metabolomics profiling have ushered in a new era of nutritional research. Metabolomics is defined as the comprehensive analysis and identification of all the different metabolites present within a biological sample.

Over 90% of diabetes cases are the type 2 form, and the condition poses a major threat to health around the world. Global prevalence of the disease in adults has more than tripled in less than two decades, with cases increasing from around 150 million in 2000 to over 450 million in 2019 and projected to rise to around 700 million in 2045.

The global health burden of T2D is further increased by the numerous complications arising from the disease, both macrovascular, such as cardiovascular disease, and microvascular, which damage the kidneys, the eyes, and the nervous system. The diabetes epidemic is primarily caused by unhealthy diets, having overweight or obesity, genetic predisposition, and other lifestyle factors such as a lack of exercise. Plant-based diets, especially healthy ones rich in high quality foods such as whole grains, fruits, and vegetables, have been associated with a lower risk of developing T2D but the underlying mechanisms involved are not fully understood.

The team conducted an analysis of blood plasma samples and dietary intake of 10,684 participants from three prospective cohorts (Nurses’ Health Study, Nurses’ Health Study II and Health Professionals Follow-up Study). Participants were predominantly white, middle-aged (mean age 54 years), and with a mean body mass index (BMI) of 25.6kg/m².

Study participants completed food frequency questionnaires (FFQs) which were scored according to their adherence to three plant-based diets: an overall Plant-based Diet Index (PDI), a healthy Plant-based Diet Index (hPDI), and an Unhealthy Plant-Based Diet Index (uPDI). Diet indices were based on that individual’s intake of 18 food groups: healthy plant foods (whole grains, fruits, vegetables, nuts, legumes, vegetable oils, and tea/coffee); unhealthy plant foods (refined grains, fruit juices, potatoes, sugar-sweetened beverages, and sweets/desserts); and animal foods (animal fats, dairy, eggs, fish/seafood, meat, and miscellaneous animal-based foods). The team distinguished between healthy and unhealthy plant foods according to their association with T2D, cardiovascular disease, certain cancers, and other conditions, including obesity and high blood pressure.

The researchers tested blood samples taken back in late 1980s and 1990s in the early phase of the three studies mentioned above to create metabolite profile scores for the participants, and any cases of incident T2D during the follow-up period of the study were recorded. Analyses of these data together with the diet index scores enabled the team to find any correlations between metabolite profile, diet index, and T2D risk.

The study found that compared with participants who did not develop T2D, those who were diagnosed with the disease during follow-up had a lower intake of healthy plant-based foods, as well as lower scores for PDI and hPDI. In addition, they had a higher average BMI, and were more likely to have high blood pressure and cholesterol levels, use blood pressure and cholesterol drugs, have a family history of diabetes, and be less physically active.

The metabolomics data revealed that plant-based diets were associated with unique multi-metabolite profiles, and that these patterns differed significantly between the healthy and unhealthy plant-based diets. In addition, metabolite profile scores for both the overall plant-based diet and the healthy plant-based diet were inversely associated with incident T2D in a generally healthy population, independent of BMI, and other diabetes risk factors, while no association was observed for the unhealthy plant-based diet. As a result, higher metabolite profile scores for PDI and hPDI indicated both closer adherence to those diets and having a lower risk of developing T2D.

Further analysis revealed that after adjusting for levels of trigonelline, hippurate, isoleucine, a small set of triacyglycerols (TAGs), and several other intermediate metabolites, the association between plant-based diets and T2D largely disappeared, suggesting that they might play a key role in linking those diets to incident diabetes. Trigonelline, for example, is found in coffee and has demonstrated beneficial effects on insulin resistance in animal studies, while higher levels of hippurate are associated with better glycaemic control, enhanced insulin secretion and lower risk of T2D. The team suggest that these metabolites could be investigated further and may provide mechanistic explanations of how plant-based diets can have a beneficial effect on T2D risk.

Professor Hu explains: “While it is difficult to tease out the contributions of individual foods because they were analysed together as a pattern, individual metabolites from consumption of polyphenol-rich plant foods like fruits, vegetables, coffee, and legumes are all closely linked to healthy plant-based diet and lower risk of diabetes.”

The authors conclude: “Our findings support the beneficial role of healthy plant-based diets in diabetes prevention and provide new insights for future investigation…our findings regarding the intermediate metabolites are at the moment intriguing but further studies are needed to confirm their causal role in the associations of plant-based diets and the risk of developing type 2 diabetes.”

Since they only collected blood samples at one point in time, the authors also believe that long-term repeated metabolomics data are needed to understand how dietary changes relate to changes in metabolome, thereby influencing T2D risk.

“With the high-resolution microscopy techniques developed by us and others worldwide, we gain fascinating insights into the dynamic ultrastructure of the heart,” says the study’s lead author Dr Eva Rog-Zielinska. She heads the 4D Imaging Section at the Institute of Experimental Cardiovascular Medicine (IEKM) of the University Heart Centre at the University Medical Centre Freiburg. “We can use this insight to analyse the three-dimensional structure of heart cells with unprecedented precision. Our images are made up of cubes — so-called voxels — with an edge length of one nanometre or less. For illustration: one nanometre is the distance a fingernail grows in one second,” Rog-Zielinska explains.

Watching the heart beat in super slow motion

A challenge is to link ultra-high resolution mapping of the heart to a moving target. “Thanks to recent advances in imaging, we now have a much better understanding of how muscle and connective tissue cells behave in the beating heart,” says co-author Prof Peter Kohl, Director of the IEKM, who is also the spokesperson of the German Collaborative Research Centre 1425 dedicated to exploring cardiac scarring.

Electron microscopy itself, but crucially also newly developed methods for the preparation and post-processing of corresponding samples, play a central role in the generation of molecular insight. “It is particularly exciting that we can record muscle cells like individual frames in a film — thanks to millisecond-precise high-pressure freezing. This allows us to watch the heart’s molecular structures beating in super slow motion, as it were,” says Kohl.

Experiments, simulations and artificial intelligence intertwine

The microscopic images are evaluated at IEKM with the help of artificial intelligence, assisted by computer simulations to depict heart function and pathological changes as realistically as possible. “Newly gained insight allows us to gain a completely new understanding of cardiac activity and, based on this, to develop new therapeutic concepts. We are looking forward to a very exciting time in heart research,” says Kohl.

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Climate scientists count the Atlantic Meridional Overturning Circulation (or AMOC) among the biggest tipping points on the way to a planetary climate disaster. The Atlantic Ocean current acts like a conveyor belt carrying warm tropical surface water north and cooler, heavier deeper water south.

“We’ve been taught to picture it like a conveyor belt — even in middle school and high school now, it’s taught this way — that shuts down when freshwater comes in from ice melt,” says Feng He, an associate scientist at UW-Madison’s Center for Climatic Research.

However, building upon previous work, He says researchers are revising their understanding of the relationship between AMOC and freshwater from melting polar ice.

In the past, a stalled AMOC has accompanied abrupt climate events like the Bølling-Allerød warming, a 14,500-year-old, sharp global temperature hike. He successfully reproduced that event using a climate model he conducted in 2009 while a UW-Madison graduate student.

“That was a success, reproducing the abrupt warming about 14,700 years ago that is seen in the paleoclimate record,” says He, now. “But our accuracy didn’t continue past that abrupt change period.”

Instead, while Earth’s temperatures cooled after this abrupt warming before rising again to plateau at new highs for the last 10,000 years, the 2009 model couldn’t keep pace. The simulated warming over the northern regions of the planet didn’t match the increase in temperatures seen in geological archives of climate, like ice cores.

In a study published this week in the journal Nature Climate Change, He and Oregon State University paleoclimatologist Peter Clark describe a new model simulation that matches the warmth of the last 10,000 years. And they did it by doing away with the trigger most scientists believe stalls or shuts down the AMOC.

Warming temperatures on Earth’s surface cause sea ice in the Arctic Ocean and the Greenland Ice Sheet to melt, releasing fresh water into the ocean. Scientists widely believed that the freshwater influx disrupts the density differences in the North Atlantic that make the AMOC’s north-bound water sink and turn back south.

“The problem,” says He, “is with the geological climate data.”

Though the climate record shows an abundance of freshwater that came from the final melting of the ice sheets over North America and Europe, the AMOC barely changed. So, He removed the assumption of a freshwater deluge from his model.

“Without the freshwater coming in making the AMOC slow down in the model, we get a simulation with much better, lasting agreement with the temperature data from the climate record,” He says. “The important result is that the AMOC appears to be less sensitive to freshwater forcing than has long been thought, according to both the data and model.”

This is particularly important to climate models that evaluate how the AMOC will respond to future increases of freshwater from ice melt.

“It’s built into many models,” He says. “Future global warming from increasing carbon dioxide in the atmosphere melts sea ice, and the freshwater from the melting ice is believed to cause the AMOC to weaken.”

The widespread consequences of a drastic weakening of the AMOC include rapid sea-level rise on the eastern coast of North America, cooling over Europe that could disrupt agriculture, a parched Amazon rainforest and disruption of Asian monsoons. The new modeling study anticipates a much smaller reduction in AMOC strength, but that doesn’t rule out abrupt change.

“We suggest until this challenge is solved, any simulated AMOC changes from freshwater forcing should be viewed with caution,” He says. “We can’t be certain why the AMOC shut down in the past. but we are certain it did change. And it can change again.”