Friday, January 19, 2024

Time change for biological aging clocks: How immune cells shape our body's true age


New research reveals the secret to slowing down the aging process is intricately tied to a balance in your immune system.


Peer-Reviewed Publication

DARTMOUTH HEALTH





LEBANON, NH—When asked, “How old are you?” Most people measure by how many birthdays they’ve had. But scientists have developed epigenetic clocks to measure how 'old' your body really is. At the forefront of aging research, these clocks go beyond our calendar age to try and reveal our biological age—a true marker of how healthy we are. However, scientists don't fully understand how they work. As a recent NYT article pointed out, it's a bit like having a sophisticated gadget without a manual. Our bodies' internal workings, especially our immune system, play a huge role, but the details are still unclear.

New research by Dartmouth Cancer Center scientists has taken the first step to change that. The team, led by Ze Zhang, PhD, Lucas Salas, MD, MPH, PhD, and Brock Christensen, PhD, is diving deep into the immune system to learn how different immune cells affect epigenetic clocks, to make them more accurate and reliable.

In their study, “Deciphering the role of immune cell composition in epigenetic age acceleration: Insights from cell-type deconvolution applied to human blood epigenetic clocks,” newly published in Aging Cell, the team determined how our body's biological age is related to our immune system. Using novel tools they recently developed for immune profiling, they were able to more closely examine how immune cell profiles relate with biological age estimates from epigenetic clocks. In particular, the balance between naïve and memory immune cells seems to accelerate or slow down biological aging. Key innovations of the study include:

  • Enabling the calculation of Intrinsic Epigenetic Age Acceleration (IEAA) with unprecedented immune cell granularity, allowing for a much more detailed understanding of the aging process at a cellular level.
  • Offering a more direct comparison between immune cells and aging than the traditional Extrinsic Epigenetic Age Acceleration (EEAA) method, which only considers a limited range of immune cells.
  • Adding a new layer of understanding to the biological interpretation of epigenetic clocks, by mapping out how various immune cell subsets contribute to epigenetic aging and providing insights that previous research has missed.

“Our findings open new doors to a much more detailed understanding of the relationships between the immune system and biological age at a cellular level, and the internal and external factors that influence how quickly we age,” says Zhang.

The implications of these findings are far-reaching, offering new insights into the aging process and potential pathways for health interventions. Future studies will focus on incorporating groundbreaking findings that link immune cell composition to epigenetic aging into calculating biological age using epigenetic clocks—a significant shift in how we evaluate biological age that will ensure a more comprehensive and accurate assessment.

Upcoming research will delve directly into different immune cells' roles in various disease settings, particularly in different types of cancer. By unraveling the complex roles of immune cells influenced by epigenetic aging, the team’s research could lead to more targeted and effective cancer treatments, a deeper understanding of how cancer develops, and new approaches for precision cancer prevention.

“This exciting trajectory can transform our understanding of disease and aging and open new possibilities in precision prevention, precision medicine, and targeted treatments,” says Zhang. “With these steps, we move closer to a future where predicting and preventing diseases like cancer becomes more precise and effective, guided by the deepened knowledge of biological age and the immune system.”

 

Ze Zhang, PhD, is the lead author of the paper. His research interests include molecular epidemiology, specifically epigenetics in cancer, developmental biology, immunology, and cell heterogeneity.

Lucas Salas, MD, MPH, PhD, is a member of of Dartmouth Cancer Center’s Cancer Population Sciences Research Program, and Assistant Professor of Epidemiology at Dartmouth’s Geisel School of Medicine. His research interests include investigation into how cell heterogeneity impacts human health and disease, with an emphasis on genetic, environmental and lifestyle factors. @lsalas_epigenet

Brock C. Christensen, PhD, Co-Leads the Cancer Population Sciences Research Program at Dartmouth Cancer Center, and is a Professor of Epidemiology, Professor of Community and Family Medicine, and Professor of Molecular and Systems Biology at Dartmouth’s Geisel School of Medicine. His research interests include understanding relationships between epigenetic states and exposures in the context of disease susceptibility, occurrence, and progression. @Brockclarke

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About Dartmouth Cancer Center: Dartmouth Cancer Center combines the advanced cancer research in partnership with Dartmouth and the Geisel School of Medicine, with award-winning, personalized, and compassionate patient-centered cancer care based at the Norris Cotton Cancer Care Pavilion at Dartmouth Hitchcock Medical CenterWith 14 locations around New Hampshire and Vermont, Dartmouth Cancer Center is one of only 56 National Cancer Institute-designated Comprehensive Cancer Centers. Each year the Dartmouth Cancer Center schedules 74,000 appointments seeing more than 4,500 newly diagnosed patients and currently offers patients more than 240 active clinical trials. Celebrating its 50th anniversary in 2022, Dartmouth Cancer Center remains committed to excellence, outreach and education. We strive to prevent and cure cancer, enhance survivorship and to promote cancer health equity through pioneering interdisciplinary research and collaborations. Learn more at http://cancer.dartmouth.edu.

Surprisingly simple model explains how brain cells organize and connect

ANARCHY IS IN YOUR HEAD

Scientists from UChicago, Harvard, and Yale propose a self-organizing model of connectivity that applies across a wide range of organisms and potentially other types of networks as well.

@ IS SELF ORGANIZATION



UNIVERSITY OF CHICAGO





A new study by physicists and neuroscientists from the University of Chicago, Harvard and Yale describes how connectivity among neurons comes about through general principles of networking and self-organization, rather than the biological features of an individual organism.

The research, published on January 17, 2024 in Nature Physics, accurately describes neuronal connectivity in a variety of model organisms and could apply to non-biological networks like social interactions as well.

“When you’re building simple models to explain biological data, you expect to get a good rough cut that fits some but not all scenarios,” said Stephanie Palmer, PhD, Associate Professor of Physics and Organismal Biology and Anatomy at UChicago and senior author of the paper. “You don’t expect it to work as well when you dig into the minutiae, but when we did that here, it ended up explaining things in a way that was really satisfying.”

Understanding how neurons connect

Neurons form an intricate web of connections between synapses to communicate and interact with each other. While the vast number of connections may seem random, networks of brain cells tend to be dominated by a small number of connections that are much stronger than most.

This “heavy-tailed” distribution of connections (so-called because of the way it looks when plotted on a graph) forms the backbone of circuitry that allows organisms to think, learn, communicate and move. Despite the importance of these strong connections, scientists were unsure if this heavy-tailed pattern arises because of biological processes specific to different organisms, or due to basic principles of network organization.

To answer these questions, Palmer and Christopher Lynn, PhD, Assistant Professor of Physics at Yale University, and Caroline Holmes, PhD, a postdoctoral researcher at Harvard University, analyzed connectomes, or maps of brain cell connections. The connectome data came from several different classic lab animals, including fruit flies, roundworms, marine worms and the mouse retina.

To understand how neurons form connections to one another, they developed a model based on Hebbian dynamics, a term coined by Canadian psychologist Donald Hebb in 1949 that essentially says, “neurons that fire together, wire together.” This means the more two neurons activate together, the stronger their connection becomes.

Across the board, the researchers found these Hebbian dynamics produce “heavy-tailed” connection strengths just like they saw in the different organisms. The results indicate that this kind of organization arises from general principles of networking, rather than something specific to the biology of fruit flies, mice, or worms.

The model also provided an unexpected explanation for another networking phenomenon called clustering, which describes the tendency of cells to link with other cells via connections they share. A good example of clustering occurs in social situations. If one person introduces a friend to a third person, those two people are more likely to become friends with them than if they met separately.

"These are mechanisms that everybody agrees are fundamentally going to happen in neuroscience,” Holmes said. “But we see here that if you treat the data carefully and quantitatively, it can give rise to all of these different effects in clustering and distributions, and then you see those things across all of these different organisms.”

Accounting for randomness

As Palmer pointed out, though, biology doesn’t always fit a neat and tidy explanation, and there is still plenty of randomness and noise involved in brain circuits. Neurons sometimes disconnect and rewire with each other — weak connections are pruned, and stronger connections can be formed elsewhere. This randomness provides a check on the kind of Hebbian organization the researchers found in this data, without which strong connections would grow to dominate the network.

The researchers tweaked their model to account for randomness, which improved its accuracy.

“Without that noise aspect, the model would fail,” Lynn said. “It wouldn’t produce anything that worked, which was surprising to us. It turns out you actually need to balance the Hebbian snowball effect with the randomness to get everything to look like real brains.”

Since these rules arise from general networking principles, the team hopes they can extend this work beyond the brain.

“That’s another cool aspect of this work: the way the science got done,” Palmer said. “The folks on this team have a huge diversity of knowledge, from theoretical physics and big data analysis to biochemical and evolutionary networks. We were focused on the brain here, but now we can talk about other types of networks in future work.”

The study, “Heavy–tailed neuronal connectivity arises from Hebbian self–organization,” was supported by the National Science Foundation, through the Center for the Physics of Biological Function (PHY–1734030) and a Graduate Research Fellowship (C.M.H.); by the James S. McDonnell Foundation through a Postdoctoral Fellowship Award (C.W.L.); and by the National Institutes of Health BRAIN initiative (R01EB026943).


Fastest swimming insect could inspire uncrewed boat designs


Peer-Reviewed Publication

CORNELL UNIVERSITY





ITHACA, N.Y. – Whirligig beetles, the world’s fastest-swimming insect, achieve surprising speeds by employing a strategy shared by speedy marine mammals and waterfowl, according to a new Cornell University study that rewrites previous explanations of the physics involved.

The centimeter-long beetles can reach a peak acceleration of 100 meters per second and a top velocity of 100 body lengths per second (or one meter per second).

Not only do the results explain the whirligig’s Olympian speeds, but they also offer valuable insights for bio-inspired designers of near-surface water robots and uncrewed boats.

Until now, researchers have believed that whirligigs attain their impressive speeds using a propulsion system called drag-based thrust. This type of thrust requires the insect’s legs to move faster than the swimming speed, in order for the legs to generate any thrust. For the whirligig beetle to achieve such fast swimming speeds, its legs would need to push against the water at unrealistic speeds.

“It could have well been questioned,” said Chris Roh, assistant professor of biological and environmental engineering. “The fastest swimmer and drag-based thrust don’t usually go together in the same sentence.”

In fact, fast-swimming marine mammals and waterfowls tend to forgo drag-based thrust in favor of lift-based thrust, another propulsion system. The finding was described in a study published Jan. 8 in the journal Current Biology.

Using two high-speed cameras synchronized at different angles, the researchers were able to film a whirligig and observe a lift-based thrust mechanism at play. Lift-based thrust works like a propeller, where the thrusting motion is perpendicular to the water surface, eliminating drag and allowing for more efficient momentum capable of greater speed.

Lift-based thrust has previously been identified in large-scale organisms, such as whales, dolphins and sea lions. “In this work, we extended the length-scale down to one centimeter, which means that whirligig beetles are by far the smallest organism to use lift-based thrust for swimming,” said Yukun Sun, a doctoral student in Roh’s lab and the paper’s first author.

“We’re hoping that this speaks to bio-inspired robotics and other engineering communities to first identify the right physics and then try to preserve that physics in creating the robotics,” Roh said.

The U.S. Navy has been developing uncrewed boats, as traditional ship design is constrained by the need to make boats hospitable to a crew. By eliminating a crew, boats can be much smaller and more flexible. Roh believes that the small size, ship-like shape and lift-generating propulsion mechanism of whirligigs translate well to inform robotic ship designs.

The study was funded by the National Science Foundation.

For additional information, see this Cornell Chronicle story.

Media note: Video of the whirligig beetle can be viewed and downloaded here: https://cornell.box.com/v/whirligigbeetles 

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UC Study: Thirdhand smoke may harm children


UC researcher Ashley Merianos says toxic substances remain on surfaces, even in homes that ban indoor smoking


Peer-Reviewed Publication

UNIVERSITY OF CINCINNATI

Ashley Merianos 

IMAGE: 

ASHLEY MERIANOS, PHD, ASSOCIATE PROFESSOR IN UC’S SCHOOL OF HUMAN SERVICES.

view more 

CREDIT: ANDREW HIGLEY/UC MARKETING + BRAND





It’s long been established that secondhand smoke is a detriment to health and linked to cancer.

Now, researchers are looking more closely at thirdhand smoke, which is the presence of toxic tobacco by-products that remain on surfaces such as furniture, décor, walls and floors.  

In a new study, published in the Journal of Exposure Science & Environmental Epidemiology, researchers tested the surfaces in smoking households where children reside and found troubling results, says Ashley Merianos, a tobacco researcher at the University of Cincinnati who led the study. 

Researchers found nicotine on surfaces in all of the children's homes and detected the presence of a tobacco-specific carcinogen (called NNK) in nearly half of the homes, she says.  

The study reported that the NNK levels on surfaces and vacuumed dust were similar, which Merianos says indicates that surfaces and dust can be similar reservoirs and sources of thirdhand smoke exposure for children.

“This is critically important and concerning, since NNK is considered the most potent carcinogen for tobacco-induced cancers,” says Merianos, an associate professor in UC’s School of Human Services.

Additional findings include:

  • Children living in lower-income households had higher levels of NNK and nicotine found on home surfaces.
  • Children living in homes that did not ban indoor smoking had higher levels of NNK and nicotine found on surfaces.

Merianos says that NNK and nicotine were still detected in homes with voluntary indoor smoking bans, which highlights the persistence of thirdhand smoke pollutants on surfaces in children's homes.

“This research highlights that home smoking bans do not fully protect children and their families from the dangers of tobacco,” she adds. 

Merianos is a prolific researcher and has extensive training and experience in the epidemiology and prevention of substance use with an emphasis on tobacco, as well as quantitative statistical methods and clinical and translational research in the pediatric health care setting. 

She is also a research affiliate member of Cincinnati Children’s Hospital Medical Center, the Thirdhand Smoke Research Consortium and the American Academy of Pediatrics Tobacco Consortium.

 

Unique framework of tin bimetal organic compound facilitates stable lithium-ion storage


Peer-Reviewed Publication

TSINGHUA UNIVERSITY PRESS

Tin-titanium-ethylene glycol (Sn-Ti-EG) anode demonstrates excellent stability and energy capacity after 700 cycles 

IMAGE: 

THE SN-TI-EG ANODE MAINTAINED A CAPACITY OF 345 MAH G-1 (BLUE LINE) AT A CURRENT DENSITY OF 1.0 A G-1 AFTER 700 CHARGE-DISCHARGE CYCLES. THE METAL-ORGANIC FRAMEWORK (MOF) OF THE SN-TI-EG ANODE MITIGATES THE TYPICAL STABILITY ISSUES OF SN AND SN-ALLOY ANODES THAT OCCUR DUE TO EXPANSION DURING THE CHARGE-DISCHARGE CYCLE.

view more 

CREDIT: ENERGY MATERIALS AND DEVICES, TSINGHUA UNIVERSITY PRESS





Battery capacity is one of the primary bottlenecks in efficient renewable energy storage and significant reductions in carbon emissions. As a battery anode that releases electrons in a lithium-ion battery (LIB), tin (Sn) and Sn-mixture alloys could theoretically store more energy at a higher density than more common carbon-based anodes. Pairing a Sn-Ti bimetal element with inexpensive ethylene glycol (Sn-Ti-EG) mitigated many of the challenges of using Sn as an anode material and produced an inexpensive LIB with excellent storage and performance characteristics.

 

Sn and Sn alloys, or mixture of another metal with Sn, could outperform other anode materials but suffer from poor stability due to the expansion of the metal during charging and discharging. One way to overcome this limitation is by creating a metal-organic framework (MOF) that maintains rapid electron transfer (energy flow) while providing good stability during charging and recharging. Materials scientists recently created a Sn-Ti-EG bimetal organic compound MOF that demonstrated high electricity conduction, energy capacity and stability through many charging and discharging cycles.

 

The researchers published their study in the journal Energy Materials and Devices on November 20.

 

“Significant efforts have been directed toward developing high-capacity cathode and anode materials for high energy-density LIBs. Because the capacities of well-known cathode materials, for example LiFePO4, Ni-rich layered oxides and LiMn2O4, have reached their theoretical limits, more attention is being focused on finding anode materials that have high energy densities as a substitute for the commonly used graphite anodes that have a relatively low theoretical capacity and tap density.” said Zhen-Dong Huang, senior author of the study and professor in the State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors at Nanjing University of Posts and Telecommunications in Nanjing, China.

 

Specifically, anodes made from graphite, a crystalline form of carbon, have a theoretical capacity of 372 mAh g-1, which refers to the amount of electric charge (milliampere hours or mAh) the material can deliver per gram (g-1) of that material. In contrast, Sn, bismuth (Bi) and antimony (Sb) metals have higher theoretical capacities than graphite anodes. Sn anodes, for example, have a theoretical capacity of 994 mAh g-1, but suffer from stability issues due to expansion.

 

“To resolve the stability issues associated with Sn anodes, a myriad of strategies have been explored, including minimizing the particle size, introducing inert metals and assembling with carbon materials. Moreover, rationally designed structures, such as hollow, layered and

core–shell structures play an important role in alleviating volume expansion. Although these strategies helped the cyclic stability to a certain degree, the… energy densities of the nanostructured Sn-based anodes are normally low. In contrast, metal–organic frameworks have an intrinsically porous structure that not only provides a large number of active sites but also enables rapid electrolyte penetration and electron/ion transfer,” said Huang.

 

The research team created a unique MOF made up of Sn, Ti and EG that leveraged beneficial characteristics of each component to create a more stable anode material with high electrochemical performance. EG, for example, served as an organic bridge between positively charged Sn2+ and Ti4+ ions to complete the battery circuit. Ti additionally contributed to the improved structure and stability of the material. Sn contributed its higher theoretical capacity, improving the anode material’s electrochemical performance.

 

Ultimately, the team created a new, inexpensive LIB anode material that maintained a high specific capacity of 345 mAh g-1 at a current density of 1000 mA g−1 after 700 cycles, which demonstrates the stability of anode material. Scanning electron microscope pictures confirmed that the anode material had no cracks after 700 cycles.

 

Further analysis of the Sn-Ti-EG anode material revealed that the strong interaction between the Sn and carbon-oxygen species was responsible for the high specific capacity and excellent cyclic stability of the electrode, which may help future researchers design additional anode materials with similar characteristics. The research team sees this latest advance in anode specific capacity as a stepping stone to additional LIB materials that can improve battery storage capacity and be produced efficiently at large scale.

 

Other contributors include Yuqing Cai, Haoran Li, Qianzi Sun, Xiang Wang and Ziquan Li from the State Key Laboratory for Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors at the Institute of Advanced Materials in the Jiangsu National Synergetic Innovation Center for Advanced Materials at the Nanjing University of Posts and Telecommunications in Nanjing, China; Haigang Liu from the Shanghai Synchrotron Radiation Facility in the Shanghai Advanced Research Institute at the Chinese Academy of Sciences in Shanghai, China; and Jang-Kyo Kim from the Department of Mechanical Engineering at Khalifa University in Abu Dhabi, United Arab Emirates.

 

This research was supported by the National Natural Science Foundation of China (52277219, 61974072, 52032005), the Project of State Key Laboratory of Organic Electronics and Informa- tion Displays, Nanjing University of Posts and Telecommunications (GZR2022010024), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_0992), Khalifa University financial support (FSU 2023-022, PD#8295), and the Shanghai Synchrotron Radiation Facility (BL07U).

 


About Energy Materials and Devices

Energy Materials and Devices is launched by Tsinghua University, published quarterly by Tsinghua University Press, aiming at being an international, single-blind peer-reviewed, open-access and interdisciplinary journal in the cutting-edge field of energy materials and devices. It focuses on the innovation research of the whole chain of basic research, technological innovation, achievement transformation and industrialization in the field of energy materials and devices, and publishes original, leading and forward-looking research results, including but not limited to the materials design, synthesis, integration, assembly and characterization of devices for energy storage and conversion etc.

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