Publisher Health

Research to understand how cancers grow and spread has conventionally been done on two-dimensional, flat cultures of cells, which is very different to the three-dimensional structure of cells in the body. 3D cell cultures that incorporate tissue material have been developed, but the methods to measure how cancer cells use forces to spread have been lacking.
Now, researchers have developed a new method for 3D culture to accurately quantify how cancer cells generate forces to spread within tissue. ‘We have applied the method for investigation of early progression of breast cancer,’ says Juho Pokki, a principal investigator at Aalto University who led the research.
This study, a collaboration between scientists at Aalto University and Stanford University, was published in the journal Nano Letters.
Nanospheres measure force pulses that accumulate into stronger forces
A primary tumour can form inside the breast’s mammary duct, where the cancerous cells are confined by a special membrane, called a basement membrane. Breast cancer cells are larger than the pores in these membranes, so they must break through to spread to other tissues. Previously, researchers thought that cells use enzymes to dissolve membranes, but now it is understood that breast cancer cells use another mechanism involving cellular protrusions to pass through the membranes.
‘In this mechanism, breast cancer cells use forces generated by the protrusions to open up channels within the membrane material. Then, the cancer cells enter the surrounding tissue and may travel further to blood vessels to spread to the rest of the body. In fact, the blood vessels are also surrounded by a basement membrane. Breast cancer cells potentially use a similar mechanism to break through into those basement membranes,’ explains Pokki. ‘Professor Ovijit Chaudhuri’s group at Stanford originally found this protrusion mechanism in 2018. Collaboration with his group has been the key for the physiological significance of this work,’ says Pokki.

The skin is one of the largest and most accessible organs in the human body, but penetrating its deep layers for medicinal and cosmetic treatments still eludes science.
Although there are some remedies — such as nicotine patches to stop smoking — administered through the skin, this method of treatment is rare since the particles that penetrate must be no larger than 100 nanometer (one thousandth of a centimeter). Creating effective tools using such tiny particles is a great challenge. Because the particles are so small and difficult to see, it is equally challenging to determine their exact location inside the body — information necessary to ensure that they reach intended target tissue. Today such information is obtained through invasive, often painful, biopsies.
A novel approach, developed by researchers at Bar-Ilan University in Israel, provides an innovative solution to overcoming both of these challenges. Combining techniques in nanotechnology and optics, they produced tiny (nanometric) diamond particles so small that they are capable of penetrating skin to deliver medicinal and cosmetic remedies. In addition, they created a safe, laser-based optical method that quantifies nanodiamond penetration into the various layers of the skin and determines their location and concentration within body tissue in a non-invasive manner — eliminating the need for a biopsy.
This innovation was just published by researchers from the University’s Institute of Nanotechnology and Advanced Materials, in cooperation with the Kofkin Faculty of Engineering and Department of Chemistry, in the scientific journal ACS Nano.
Nanodiamonds — a millionth of a millimeter in size — are produced by detonating explosives inside a closed chamber. Under these conditions high temperature and pressure cause the carbon atoms found in explosives to fuse together. The nanodiamonds created in the process are small enough to penetrate tissue — and even cells — without inflicting harm.
Nanodiamonds and drug delivery
Much like trucks that make deliveries, artificial diamonds can deliver various medications to intended targets, and their distance and location may be controlled due to the minute size of the nanodiamonds. The approach to drug delivery using nanoparticles has already proven successful in previous research.
The nanodiamonds newly-developed at Bar-Ilan University have also been proven effective antioxidants. This property ensures that particles penetrating the body are both safe and therapeutic, as their chemical properties allow them to be coated with medication prior to their insertion into the body.
Tracking nanodiamonds through optics
The optical method developed by the research team enables them to identify relative nanodiamond concentrations of particles in the different layers of skin (epidermis, dermis and fat) through safe and non-invasive sensing based on a blue wavelength laser, a unique finding in itself given the fact that red wavelength lasers are generally used in human medical exams and treatments. To determine their location in the skin and in what concentration, patients are briefly exposed to the blue laser beam. An optical system creates a photograph-like 3D image through which optical changes in treated tissue can be extracted and compared to adjacent, untreated tissue using a specially-created algorithm.
“This is a significant development in dermatology and in optical engineering,” says Prof. Dror Fixler, Director of the Institute of Nanotechnology and Advanced Materials at Bar-Ilan University and a member of the research team. “It could open the door to developing drugs applied through the skin alongside modern cosmetic preparations using advanced nanotechnology.” Fixler’s research, assisted by researcher Channa Shapira and others, demonstrates the importance of optical innovation in clinical application.
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Materials provided by Bar-Ilan University. Note: Content may be edited for style and length.

Since the beginning of the pandemic, SARS-CoV-2 has been suspected of causing chronic fatigue syndrome (ME/CFS). A well-controlled study conducted by a group of researchers from Charité — Universitätsmedizin Berlin and the Max Delbrück Center for Molecular Medicine (MDC) has now shown that, even after mild COVID-19, a subset of patients will develop symptoms which meet the diagnostic criteria for ME/CFS. Their findings also describe a second subset of post-COVID patients with similar symptoms. Differences in laboratory results between these groups may indicate differences in underlying mechanisms. The researchers’ findings have been published in Nature Communications.
“Suspicions that COVID-19 might trigger ME/CFS initially arose as early as during the first wave of the pandemic,” says Prof. Dr. Carmen Scheibenbogen, Acting Director of Charité’s Institute of Medical Immunology on Campus Virchow-Klinikum. Prof. Scheibenbogen also oversees the work of the ‘Charité Fatigue Center’, which specializes in the diagnosis of ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), a debilitating condition characterized by severe physical fatigue. The Center received its first requests from patients after SARS-CoV-2 infection as early as the summer of 2020. Since then, there has been accumulating evidence of a causal link between COVID-19 and ME/CFS, a disease which often causes severe physical impairments.
“Providing the scientific evidence to confirm these assumptions, however, is anything but a trivial task,” explains Prof. Scheibenbogen. She continues: “This is partly due to the paucity of research into ME/CFS and the fact that there are no universally accepted diagnostic criteria. Thanks to an extremely thorough diagnostic process and a comprehensive comparison with patients who developed ME/CFS following non-COVID-related infections, we have now been able to show that COVID-19 can trigger ME/CFS.”
As part of this study, experts from Charité’s Post-COVID Network examined 42 individuals who presented at the Center with persistent, severe fatigue and impaired day-to-day functioning six months after their SARS-CoV-2 infection. Most of the study participants were unable to perform light work for more than two to four hours a day; some were unable to work and struggled to look after themselves. Only three out of the 42 patients examined needed hospital care during their initial (acute) SARS-CoV-2 infection, but none required oxygen. 32 of the patients met the WHO classification of mild COVID-19, meaning they did not develop pneumonia, but had fairly severe symptoms including fever, cough, muscle pain and joint pain for between one and two weeks. As all of the participants’ infections occurred during the first wave of the pandemic, none of them had been vaccinated. At Charité, all of the individuals concerned were examined by an interdisciplinary team of neurologists, immunologists, rheumatologists, cardiologists, endocrinologists and pulmonologists with many years’ experience in the diagnosis of ME/CFS. For comparison, the researchers then examined 19 age- and gender-matched individuals who had developed ME/CFS following a similar period of illness due to a non-COVID-related infection.
The researchers used the ‘Canadian Consensus Criteria’ to establish a diagnosis of ME/CFS. “In addition to having been scientifically developed, this catalog of criteria has been proven as a reliable diagnostic tool for chronic fatigue syndrome in clinical practice,” explains the study’s other co-lead, Dr. Judith Bellmann-Strobl, who heads the multidisciplinary outpatient department at the Experimental and Clinical Research Center (ECRC), a facility jointly operated by Charité and the MDC. According to the Canadian Consensus Criteria, approximately half of the post-COVID patients examined met the diagnostic criteria for ME/CFS. While the other half presented with similar symptoms, their post-exertional malaise was milder and only lasted for a few hours. In contrast, ME/CFS patients reported post-exertional malaise which persisted into the following day. Summarizing the researchers’ findings, Dr. Bellman-Strobl says: “We can therefore distinguish between two groups of post-COVID patients with severely impaired physical functioning.”
In addition to collating data on symptoms, the researchers also determined various laboratory parameters. They then compared these with hand grip strength, which was reduced in the majority of the participants examined. “We furthermore found that individuals with milder exertional intolerance had reduced hand grip strength if they had elevated levels of the cytokine interleukin 8. In these cases, reduced muscular strength may be caused by a persistent inflammatory response,” says Prof. Scheibenbogen. “In the ME/CFS group, however, hand grip strength was correlated with the hormone NT-proBNP, which can be released by muscle cells when oxygen supply is insufficient. This suggests that, in these individuals, muscle weakness may be caused by an impaired blood supply.” According to the researchers’ preliminary observations, the two groups may also be distinguishable in terms of disease progression. “In many people whose symptoms are indicative of ME/CFS but who do not meet diagnostic criteria, symptoms appear to improve over time,” explains Prof. Scheibenbogen.
These new findings may help researchers to develop specific treatments for post-COVID syndrome (‘Long Covid’) and ME/CFS. “Our data also provide further evidence that ME/CFS is not a psychosomatic disorder but a severe physical disease which can be measured and diagnosed using objective methods,” emphasizes Prof. Scheibenbogen. “Unfortunately, current treatments for ME/CFS are purely symptomatic in nature. I would therefore urge even young people to protect themselves against SARS-CoV-2 by getting vaccinated and wearing an FFP2 mask.”

Progressive dysfunction and failure of insulin-releasing β-cells is a hallmark of type 2 diabetes (T2D). DZD researchers have now shown that diabetes resistant and -susceptible mice respond differently to a carbohydrate-rich diet. The gene expression of the beta cells of the diabetes-resistant mice changed in such a way that a protective beta cell cluster developed. In diabetic-prone mice, a failure to adjust gene expression in response to rising blood glucose levels led to increased metabolic stress and beta cell failure. The study was published in the journal Diabetes.
To investigate the mechanisms of beta cell loss in T2D, researchers at the DZD performed single-cell RNA sequencing of islets of Langerhans in two obese mouse strains that differ in their susceptibility to diabetes. Both the diabetes-prone and diabetes-resistant mice have six different groups of beta cells in their islets, which are very similar in abundance before treatment. However, after feeding a carbohydrate-rich diabetogenic diet for two days, the composition of the beta cell clusters differed significantly between the strains. The islet cells of the diabetes-resistant mice developed into a protective beta cell cluster (Beta4). This protective cluster showed indications of reduced beta cell identity (such as downregulation of the GLUT2, GLP1R and MafA genes). Characteristics of mature beta-cell expression decreased. This likely leads to lower glucose uptake and for some, even gain of the ability to divide to ultimately produce more beta cells. An in vitro knockdown of GLUT2 in beta cells led to reduced stress reactions and a decrease in apoptosis markers (apoptosis = programmed cell death). This could explain the improved survival of beta cells in diabetes-resistant mice.
In contrast, beta cells from diabetic-prone mice responded with expression changes indicative of metabolic pressure and stress in the endoplasmic reticulum. They also lacked the adaptation of gene expression towards a more dedifferentiated state. This can presumably contribute to a later loss of beta cells, which in turn contributes to the development of diabetes.
“Our study provides new clues as to why obesity does not always lead to type 2 diabetes. The ability of mice, and presumably humans as well, to respond to elevated blood glucose levels with a transient reduction in their beta cell identity appears to play a key role in protecting them from loss of function and/or apoptosis,” said Annette Schürmann, lead author of the study.
About the study
Researchers from the German Center for Diabetes Research, Helmholtz Munich and the University Hospital Carl Gustav Carus and the Medical Faculty of TU Dresden were involved in the study, which was led by the German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE).
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Materials provided by Deutsches Zentrum fuer Diabetesforschung DZD. Note: Content may be edited for style and length.

Ironically, some vaccines need their own “boosters.” Adding an ingredient called an adjuvant can help vaccines elicit a more robust immune response, better training the body to fight a pathogen. In a new study in ACS Infectious Diseases, researchers report a substance that boosted the immune response to an experimental COVID-19 shot in mice by 25 times, compared to injection with the vaccine alone.
Although the first COVID-19 shots authorized in the U.S. apply cutting-edge genetic technology, the tried-and-true strategy of using proteins from the pathogen can produce vaccines that are less expensive to make and easier to store. So far, the U.S. Food and Drug Administration has authorized only one protein-based vaccine, made by Novavax, against SARS-CoV-2. However, many currently available inoculations against other diseases rely on proteins or pieces of them, and these shots contain adjuvants to enhance their effect. Researchers have found that molecules derived from α-galactosylceramide (αGC), a compound from marine sponges, can act as adjuvants by stimulating a small population of immune cells important for defending the body against viral infections. Rui Luo, Zheng Liu and their colleagues wanted to see if they could devise a version of αGC to significantly boost the immune response elicited by a protein-based COVID-19 vaccine.
The team made four analogs of αGC and added each to an experimental vaccine containing a piece of SARS-CoV-2’s spike protein, which the virus uses to infect cells. The researchers gave mice three injections over 29 days and tracked their immune response out to 35 days. To measure the effects of the adjuvants, they looked at various aspects of immune function, including two ways the immune system eliminates pathogens: through antibodies, which are immune proteins that latch onto an invader, and T cells, which kill diseased cells. None of the four meaningfully enhanced the T cell response, but all of them produced antibodies with a much greater capacity for interfering with the virus. The analog called αGC-CPOEt led to the production of antibodies with the greatest neutralizing capacity — 25 times greater than what the vaccine could elicit without an adjuvant. These results suggest αGC-CPOEt merits further investigation as a potential adjuvant to fight COVID-19 and other infectious diseases, the researchers say.
The authors acknowledge funding from National Natural Science Foundation of China, Central China Normal University, Fundamental Research Funds for the Central Universities from Huazhong Agricultural University, and the Program of Introducing Talents of Discipline to Universities of China.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.

An artificial-intelligence (AI) model built at Mass Eye and Ear was shown to be significantly more accurate than doctors at diagnosing pediatric ear infections in the first head-to-head evaluation of its kind, a research team working to develop the model for clinical use reported.
According to a new study published August 16 in Otolaryngology-Head and Neck Surgery, the model, called OtoDX, was more than 95 percent accurate in diagnosing an ear infection in a set of 22 test images compared to 65 percent accuracy among a group of clinicians consisting of ENTs, pediatricians and primary care doctors, who reviewed the same images.
When tested in a dataset of more than 600 inner ear images, the AI model had a diagnostic accuracy of more than 80 percent, representing a significant leap over the average accuracy of clinicians reported in medical literature.
The model utilizes a type of AI called deep learning and was built from hundreds of photographs collected from children prior to undergoing surgery at Mass Eye and Ear for recurrent ear infections or fluid in the ears. The results signify a major step towards the development of a diagnostic tool that can one day be deployed to clinics to assist doctors during patient evaluations, according to the authors. An AI-based diagnostic tool can give providers, like pediatricians and urgent care clinics, an additional test to better inform their clinical decision-making.
“Ear infections are incredibly common in children yet frequently misdiagnosed, leading to delays in care or unnecessary antibiotic prescriptions,” said lead study author Matthew Crowson, MD, an otolaryngologist and artificial intelligence researcher at Mass Eye and Ear, and assistant professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School. “This model won’t replace the judgment of clinicians but can serve to supplement their expertise and help them be more confident in their treatment decisions.”
Difficult to diagnose common condition
Ear infections occur from a buildup of bacteria inside the middle ear. According to the National Institute on Deafness and Other Communication Disorders, at least five out of six children in the United States have had at least one ear infection before the age of three. When left untreated, ear infections can lead to hearing loss, developmental delays, complications like meningitis, and, in some developing nations, death. Conversely, overtreating children when they don’t have an ear infection can lead to antibiotic resistance and render the medications ineffective against future infections. This latter problem is of significant public health importance.

Changes known as epigenetic modifications play an important role in cancer development, among other things. Being able to analyze them quickly and reliably could, for example, contribute significantly to the further development of personalized therapy. A research team from the Institute of Physiology at the University of Freiburg has now succeeded in characterizing the chemical changes in proteins that are typical for epigenetic modifications using nanopore analysis. The researchers have published their research results in the Journal of the American Chemical Society (JACS).
In recent years, nanopores have become a widely applicable tool for the analysis of molecules. Due to their special properties, they allow the structure of molecules to be analyzed within fractions of a second: As cylindrically arranged proteins, nanopores form tiny channels only a few millionths of a millimeter (nanometer) in diameter that can be embedded in biomembranes. “For the experiments, we apply a constant voltage across the membrane so that ions from the surrounding medium flow through the pore. This creates a constant, precisely measurable electric current” explains Prof. Dr. Jan C. Behrends from the Faculty of Medicine at the University of Freiburg, in whose laboratory the now-published experiments took place. However, when a molecule migrates into the pore, the current is blocked: the larger the molecule, the more strongly it is blocked too.
A protein in the research spotlight: H4
In the context of the experiments now published, the Freiburg scientists devoted themselves to the investigation of the so-called histone protein H4. This protein is firmly associated with DNA in all cells with a nucleus and is one of the best-researched targets of epigenetic modifications. A region at the N-terminal end of the protein is particularly affected by these modifications. “The protein sequence there contains the amino acid lysine several times,” Behrends explains. Acetyl or methyl groups, for example, can be attached to these lysines, which are designated K8, K12 and K16 according to their position in the protein chain, as part of epigenetic modifications. Which chemical modification takes place at which lysine position is definitely of medical importance, as the Freiburg physiologist points out. “Acetylation at K16, for example, is important for human development, while methylation at K12 plays a role in the development of some prostate and lung tumors, according to the latest results from Medical Center — University of Freiburg.”
Detecting changes with the help of a nanopore
In their experiments, Behrends and his team were now able to clearly distinguish H4 fragments with or without acetylation, as well as fragments with one, two or three acetylations. Moreover, they succeeded in demonstrating that the nanopore they used was also sensitive to the site of acetylation: histone fragments with an acetyl group at K8 blocked current through the pore more strongly than those acetylated at K12, and these in turn more strongly than those with a K16 acetylation. “This kind of sensitivity is surprising in that these fragments are identical in terms of their mass and total volume,” Behrends says. Thus, the pore current appears to be sensitive not only to the size, but also to the shape of the molecule. It was equally easy to distinguish between the different variants of doubly acetylated histone fragments — K8 and K12, K8 and K16, and K12 and K16 — again, despite the identical mass. H4 fragments methylated to different extents and at different positions also blocked the current through the pore to different degrees, although not as clearly as the acetylated variants.
“We have been able to show for the first time through our experiments that nanopore analytics allows us to distinguish molecules not only by their size, but also by their shape,” summarizes study leader Behrends. Molecular dynamics simulations conducted by the research group led by Aleksei Aksimentiev from the University of Illinois in the US — also involved in the study- and show that a highly inhomogeneous electric field inside the pore plays a key role for this effect.
Future vision: optimized medical diagnostics
While the sequencing of DNA using nanopores is already established and commercialized, the development of nanopore-based analysis of proteins is just beginning, Behrends emphasizes. “The difficulty with sequencing proteins is that these are molecules with very non-uniform charge patterns.” While DNA, which is negatively charged, migrates directionally in the electric field and can thus be pulled through the pore base by base, proteins consist of building blocks made of the amino acids with different charges. As a result, directed movement in the electric field and “scanning” amino acid by amino acid is not possible. The Freiburg scientists therefore relied on a different approach for their experiments. Instead of a pore with a short constriction, as used in DNA sequencing, they used a tailor-made pore with a kind of molecular trap. “This allowed the entire protein fragment to be captured at once,” says Behrends.
It is not yet clear up to which fragment size this type of analysis can be used. However, additional experiments show that the method will also be suitable for the analysis of the H4 fragments previously used in epigenetic research. These contain 14 amino acids instead of the ten used here, and are currently investigated for epigenetic modifications with tandem mass spectrometry, a highly elaborate technique. The researchers hope that the nanopores will make the analysis much simpler, faster and more cost-effective, and that it can be carried out close to the patient.
The further development of nanopore analysis of proteins for medical diagnostics and its implementation in concrete products and services is also one of the central projects of the recently approved BMBF Cluster4Future nanodiagBW, which Behrends heads together with Prof. Dr. Felix von Stetten of the Hahn-Schickard-Gesellschaft, which is the lead for this project.

Researchers at Aalto University have developed a bio-based adhesive that can replace formaldehyde-containing adhesives in wood construction. The main raw material in the new adhesive is lignin, a structural component of wood and a by-product of the pulp industry that is usually burned after wood is processed. As an alternative to formaldehyde, lignin offers a healthier and more carbon-friendly way to use wood in construction.
The carbon footprint of timber construction is significantly lower than concrete construction, and timber construction has often been viewed as better for the health of human occupants as well. However, wood panels still use adhesives made from fossil raw materials. They contain formaldehyde, which can be harmful to health, especially for those working in the adhesive manufacturing process. People living in or visiting buildings can also be exposed to toxic formaldehyde from wood panels.
Lignin, on the other hand, comes from wood itself. It binds cellulose and hemicellulose together and gives wood its tough, strong structure. Lignin accounts for about a quarter of the weight of wood and is produced in huge quantities in the pulp and bioprocessing industry. Only two to five percent of the lignin produced is used, and the rest is burned in factories for energy.
Previously, lengthy and chemical-intensive pre-treatments have been necessary to use lignin in formaldehyde-free adhesives. The adhesive developed by Aalto University researchers can use purified kraft lignin and the chemical reaction to make the adhesive takes a few minutes instead of up to 10 hours. No additional heating of the raw material is needed, which reduces energy consumption. The only by-products of the process are salt and sodium hydroxide, or lye.
Monika Österberg, professor at the Aalto University School of Chemical Engineering, stresses that this is an important development for both the environment and industry. ‘Using lignin as a material can reduce carbon dioxide emissions and increase the processing value of forests. This is why research on lignin is an important priority for us at Aalto University.’
Doctoral researcher Alexander Henn explains that glued wood panels such as plywood and chipboard are increasingly used for walls, ceilings and flooring. ‘Therefore, it is important to overcome the disadvantages of wood-based panel adhesives and develop the new innovation into a commercial product. This would enable a shift towards more wood-based construction, as a strong and heat-resistant adhesive made from natural materials makes construction truly ecological and safe.’
The innovation is a major step forward for the forestry and glue industries, as the lignin content of previous adhesives has been relatively low (around 20-50 percent), while the new Aalto University innovation has a lignin content of over 90 percent. The adhesive is strong and non-toxic, and protects surfaces from fire, so it can even be used as a flame retardant.
According to the researchers, lignin can also be used as a raw material for applications such as coatings and composites. Research work will continue in the laboratory, and various commercialization opportunities are likely to be explored in collaboration with LignoSphere Oy, a spin-off from Aalto University.
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Materials provided by Aalto University. Original written by Virpi Raski. Note: Content may be edited for style and length.

Among people older than age 65 who were assessed using a short physical function test, having lower physical function was independently associated with a greater risk of developing heart attack, heart failure and stroke, according to new research published today in the Journal of the American Heart Association, an open access, peer-reviewed journal of the American Heart Association.
The Short Physical Performance Battery (SPPB) used in this study is considered a measure of physical function, which includes walking speed, leg strength and balance. This study examined physical function, which is different from physical fitness.
“While traditional cardiovascular disease risk factors such as high blood pressure, high cholesterol, smoking or diabetes are closely linked to cardiovascular disease, particularly in middle-aged people, we also know these factors may not be as predictive in older adults, so we need to identify nontraditional predictors for older adults,” said study senior author Kunihiro Matsushita, M.D., Ph.D., an associate professor in the department of epidemiology at the Johns Hopkins Bloomberg School of Public Health and the Division of Cardiology at the Johns Hopkins School of Medicine in Baltimore. “We found that physical function in older adults predicts future cardiovascular disease beyond traditional heart disease risk factors, regardless of whether an individual has a history of cardiovascular disease.”
The Atherosclerosis Risk in Communities (ARIC) study, an ongoing community-based cohort enrolled 15,792 participants, ages 45-64 years from 1987-1989, to investigate the causes for atherosclerotic disease (plaque or fatty buildup in the arteries). Yearly and semi-yearly (beginning in 2012) check-ins included phone calls and in-person clinic exams.
The present study evaluated health data from ARIC visit 5 (2011-2013; all participants were older than age 65) as a baseline, when the SPPB physical function test was first collected. The SPPB measured physical function to produce a score according to walking speed, speed of rising from a chair without using your hands and standing balance.
Researchers analyzed health data for 5,570 adults (58% women; 78% white adults; 22% Black adults), average age of 75 from 2011 to 2019. Using SPPB scores, the physical function of the participants was categorized into three groups: low, intermediate and high, based on their test performance.

The decline during the pandemic is the sharpest in nearly 100 years, hitting American Indian and Native Alaskan communities particularly hard.The average life expectancy of Americans fell precipitously in 2020 and 2021, the sharpest two-year decline in nearly 100 years and a stark reminder of the toll exacted on the nation by the continuing coronavirus pandemic.In 2021, the average American could expect to live until the age of 76, federal health researchers reported on Wednesday. The figure represents a loss of almost three years since 2019, when Americans could expect to live, on average, nearly 79 years.The reduction has been particularly steep among Native Americans and Alaska Natives, the National Center for Health Statistics reported. Average life expectancy in those groups was shortened by four years in 2020 alone.The cumulative decline since the pandemic started, more than six and a half years on average, has brought life expectancy to 65 among Native Americans and Alaska Natives — on par with the figure for all Americans in 1944.In 2021, the shortening of life span was more pronounced among white Americans than among Black Americans, who saw greater reductions in the first year of the pandemic.While the pandemic has driven most of the decline in life expectancy, a rise in accidental deaths and drug overdoses also contributed, as did deaths from heart disease, chronic liver disease and cirrhosis, the new report found.Until now, experts have been accustomed to measuring life expectancy changes in increments of months, not years.“Even small declines in life expectancy of a tenth or two-tenths of a year mean that on a population level, a lot more people are dying prematurely than they really should be,” said Robert Anderson, chief of mortality statistics at the N.C.H.S.“This signals a huge impact on the population in terms of increased mortality,” he added.Dr. Steven Woolf, director emeritus of the Center on Society and Health at Virginia Commonwealth University, characterized the diminution of life expectancy in the United States as “historic.”While other high-income countries were also hard hit in 2020, the first year of the pandemic, most had begun to recover by last year, he said.Read More on the Coronavirus PandemicBoosters: Updated coronavirus vaccines are expected soon after Labor Day. But money to distribute the shots has dried up, as America’s vaccination program is feeling the effects of a long period of retreat.Moderna’s Lawsuits: The vaccine manufacturer sued Pfizer and BioNTech, claiming that its rivals’ Covid-19 shot copied groundbreaking technology that Moderna had developed before the pandemic.Fauci to Step Down: Dr. Anthony S. Fauci, President Biden’s top medical adviser who was catapulted into the spotlight at the start of the pandemic, said he would leave government service by the end of the year.New C.D.C. Guidelines: The agency loosened its Covid-19 guidance, saying those exposed to the virus no longer need to quarantine.“None of them experienced a continuing fall in life expectancy like the U.S. did, and a good number of them saw life expectancy start inching back to normal,” Dr. Woolf said.Those countries had more successful vaccination campaigns and populations that were more willing to take behavioral measures to prevent infections, such as wearing masks, he said, adding: “The U.S. is clearly an outlier.”A candle vigil held last year in Gilbert, Ariz., for people who died of overdoses.Alberto Mariani/Cronkite News, via Associated PressBut the coronavirus was not solely to blame. Longstanding health problems — rooted in poverty, discrimination and poor access to health care — left Native Americans and Alaska Natives particularly vulnerable to the virus, said Dr. Ann Bullock, former director of diabetes treatment and prevention at the federal Indian Health Service agency and a member of the Minnesota Chippewa Tribe.One in seven Native Americans and Alaska Natives has diabetes, the highest rate among racial or ethnic groups in the United States, and many struggle with obesity or excess weight. Both conditions make people more susceptible to severe Covid-19, and crowded multigenerational housing adds to the risk.“There is no doubt Covid was a contributor to the increase in mortality during the last couple of years, but it didn’t start these problems — it made everything that much worse,” Dr. Bullock said.Average life expectancy in these populations is now “lower than that of every country in the Americas except Haiti, which is astounding,” said Noreen Goldman, professor of demography and public affairs at the Princeton School of Public and International Affairs.The continued plunge was all the more upsetting because it occurred after a successful vaccination campaign, she said, adding: “The Native American population did quite well in the vaccination efforts, and that made us feel that 2021 would not be as devastating as 2020.”“That was wrong, and it’s pretty hard to swallow,” she added.White Americans saw the second-largest decline in average life expectancy in 2021, a drop of one year, to 76.4 in 2021 from 77.4 in 2020. The decline was steeper than that among Black Americans, at seven-tenths of a year. That was followed by Hispanic Americans, whose life expectancy dropped only two-tenths of a year in 2021.But both Black and Hispanic Americans were hit hard in 2020, the first year of the pandemic. Average life expectancy for Hispanic Americans fell by four years, to 77.9 from 81.9 in 2019. The figure for Black Americans declined almost as much, by more than three years to 71.5 years in 2020.White Americans experienced the smallest decline during the first year of the pandemic, a drop of 1.4 years to 77.4 from 78.8. For white and Black Americans, life expectancy is now the lowest it has been since 1995, federal researchers said.Asian Americans held the highest life expectancy among racial and ethnic groups included in the new analysis: 83.5 years, on average. The figure fell only slightly last year, from 83.6 in 2020.It was the largest reduction in life expectancy in the United States over the course of a two-year period since the early 1920s, when life expectancy fell to 57.2 in 1923. That drop-off may have been related to high unemployment and suicide rates during an earlier recession, as well as a steep increase in mortality among nonwhite men and women.Although the U.S. health care system is among the best in the world, Americans suffer from what experts have called “the U.S. health disadvantage,” an amalgam of influences that erode well-being, Dr. Woolf said.These include a fragmented, profit-driven health care system; poor diet and a lack of physical activity; and pervasive risk factors such as smoking, widespread access to guns, poverty and pollution. The problems are compounded for marginalized groups by racism and segregation, he added.The result is a high disease burden among Americans, and shorter life expectancy compared with that in comparable high-income nations over the last two decades, Dr. Woolf said.Over a million Americans have died of Covid-19, and more died in 2021 than in 2020 despite the availability of vaccines. To date, only two-thirds of Americans are fully vaccinated, and only one-third have had a booster shot.“The white population did worse in 2021 than communities of color, besides Native American and Alaska Natives,” Dr. Woolf said. “I think that’s very telling: It reflects the greater efforts by Black and Hispanics to get vaccinated, to wear masks and take other measures to protect themselves, and the greater tendency in white populations to push back on those behaviors.”The longevity gap between men and women also grew by a couple of months in 2021. American women can now expect to live 79.1 years, almost six years longer than men, whose average life expectancy was 73.2 last year, according to the new data.The longevity gap between the sexes has been increasing for more than a decade, after narrowing between 2000 and 2010 to about five years.