The Tokyo Metropolitan Institute of Gerontology

An updated analysis of American COVID-19 deaths throughout 2021 highlights a continued drop in overall life expectancy as well as persistent disparities by race and ethnicity. An updated analysis of American COVID-19 deaths throughout 2021 highlights a continued drop in overall life expectancy as well as persistent disparities by race and ethnicity. Lead author Theresa Andrasfay, a postdoctoral scholar at the University of Southern California Leonard Davis School of Gerontology, and coauthor Noreen Goldman at the Princeton School of Public and International Affairs first examined the pandemic's effect on U.S. life expectancy in October 2020. Their initial study, published in Proceedings of the National Academy of Sciences in January 2021, showed that 2020 presented the largest single-year decline in life expectancy in at least 40 years and the lowest life expectancy estimated since 2003. The updated analysis, published in PLOS ONE, indicates that U.S. life expectancy at birth decreased by 2.2 years from 78.8 in 2019 to 76.6 in 2021. The estimated decrease in life expectancy for 2021 is 0.6 years larger than the decrease observed in 2020, Andrasfay said. "Despite the availability of effective vaccines, life expectancy continued to decline in 2021. Part of this is due to the large number of COVID-19 deaths that occurred in the beginning of 2021, before many individuals were eligible for vaccination," she said. "But even once all adults became eligible for vaccination, many chose not to be vaccinated and even vaccinated individuals were not completely protected against the highly transmissible Delta and Omicron variants." The study highlighted that significant racial disparities in loss of lifespan have endured throughout the pandemic. Between 2019 and 2021, non-Latino whites lost 2 years on average, while non-Latino Blacks lost 3.5 years and Latinos lost 3.7 years of life expectancy. As noted in Andrasfay and Goldman's previous analyses, Black and Latino Americans have experienced a disproportionate burden of coronavirus infections and deaths, reflecting persistent structural inequalities that heighten risk of exposure to and death from COVID-19. Goldman noted that "although Whites experienced a larger drop in life expectancy between 2020 and 2021 than the Black and Latino populations, resulting in a very modest reduction in racial and ethnic differences, the disparities in life expectancy loss since the start of the pandemic remain regrettably and unacceptably large." Although COVID-19 is the primary cause of continued life expectancy reductions in 2021, "increases in other causes of death relative to pre-pandemic levels contribute to these life expectancy declines," the authors wrote. The pandemic appears to have played a role in the increase of drug overdose deaths in 2020 and 2021, and increased mortality from conditions such as heart disease or diabetes may be attributable to complications of Covid-19 infections and/or health care shortages and delays. This week the CDC also released provisional estimates of life expectancy in 2021. "We did not have access to the same level of detailed data as the CDC, so we arrived at slightly different life expectancy estimates," Andrasfay said. "Despite these differences, our results are largely in agreement in that we find continued life expectancy reductions in 2021 and persistent racial and ethnic disparities." "COVID-19 mortality has been lower in the first half of 2022 compared to 2021, so if there is a successful booster campaign in the fall and the dominant strains have lower fatality rates than previous variants, it is possible that 2022 life expectancy may improve relative to 2021, though it is unlikely to return to levels seen prior to 2020," she added. "However, what happens with 2022 life expectancy will ultimately depend on this coming fall and winter."

Photo Courtesy of CohBar, Inc. CohBar, Inc. is pioneering mitochondrial-based therapies with a candidate in a Phase Ia/Ib clinical trial as a potential treatment for nonalcoholic steatohepatitis (NASH) and obesity, where top-line results are expected later this year. A potential therapy for acute respiratory distress syndrome (ARDS) also is in preclinical development, along with other candidates that have the potential to enter Phase I trials in 2022. The mitochondria offer a new approach to targeting diseases. The mitochondrial genome is 200,000 times smaller than the nuclear genome and has been largely overlooked by researchers. CohBar discovered that the mitochondrial genome encodes small peptides, some of which affect other systems in the body. One of its notable programs focuses on COVID-19-triggered ARDS. “Our novel CB5064 analogs are based on a particular mitochondrial gene sequence that generates a peptide capable of binding to the apelin receptor,” Steven Engle, CEO and director, told BioSpace. That receptor affects multiple downstream processes implicated in protecting animals in preclinical models from respiratory disease, including potentially the cytokine storm that occurs in severe cases of COVID-19. Apelin is abundant in the lung, as well as in the heart, liver, and kidney. In animal models of ARDS, modulating the apelin receptor with CohBar’s novel compounds showed positive results, reducing the levels of fluid accumulation in the lungs, neutrophil infiltration, and cytokine secretion. In January, a few months after those results were announced, CohBar signed a Non-Clinical Evaluation Agreement with the National Institute of Allergy and Infectious Diseases (NIAID) to allow testing of its CB5064 analogs in animal models of COVID-19-associated ARDS. Other preclinical programs address cancer, including targeting the CXCR4 pathway that is critical to growth and metastasis of many tumors. In animal models, when a standard chemotherapy drug and CohBar’s novel CXCR4 inhibitor (a CB5046 analog) were co-administered, the combination was more effective at reducing melanoma size than chemotherapy alone. “That particular molecule has a nanomolar binding affinity, so it’s highly potent,” Engle said. “But why would the mitochondria genome encode a peptide with nanomolar binding affinity? We believe the mitochondria are directly regulating an important pathway in cancer. Nobody understood that until now.” CohBar also is developing CB5138 analogs with potential for treating idiopathic pulmonary fibrosis (IPF), a chronic, progressive, debilitating and usually fatal interstitial lung disease that affects approximately 100,000 people in the U.S., and other fibrotic diseases. Engle said he expects that therapy to enter clinical trials next year. “We still have to run the necessary pre-IND studies.” Unlike some nuclear DNA-based therapies, CohBar’s mitochondria-based therapies do not edit the mitochondrial genome, he said. Instead, they use the same pathways that mitochondria regulate by adapting mitochondrial peptides, building on millions of years of evolution. The natural peptides are often quite short-lived, with half-lives of a few minutes, but the analogs developed by CohBar have extended half-lives. The natural origin of these analogs also has the potential to result in safer molecules with fewer off-target effects than other approaches. CohBar’s research, alongside that of a few additional companies, is changing the way scientists think about the mitochondria. “For 60 years people thought the mitochondria were primarily the cell’s powerhouses,” Engle said. Yet research shows they are much more important. For example, published studies have shown that some of the peptides produced in the mitochondria affect signaling within and between cells, and regulating multiple biological systems, including, possibly, metabolism and the immune system, cell growth, and cell death. Mitochondrial dysfunction can reduce both production of energy in the form of ATP and the production of mitochondrial peptides, contributing to disease. So far, NASH, obesity, type 2 diabetes, cardiovascular and neurodegenerative diseases, cancer, immune system and inflammatory disorders, fibrotic diseases, and acute respiratory distress syndrome (ARDS) have been linked to mitochondrial disorders. CohBar’s founders Pinchas Cohen, M.D., dean of the University of Southern California’s Davis School of Gerontology and Nir Barzilai, M.D., director of the Institute for Aging Research at the Albert Einstein College of Medicine of Yeshiva University, created this new field of therapeutics when they discovered a series of peptides encoded within the mitochondria. Some of those peptides affected metabolic regulation and protection, contributing to age-related diseases. CohBar (a combination of their surnames) was founded in 2009. Since then, researchers at CohBar have discovered more than 100 new peptides encoded in the mitochondrial genome with possible therapeutic potential. Currently, CohBar is evaluating the library of peptides encoded in the mitochondrial DNA. “We believe that because they are so few that are active, many of them may be important,” Engle said. The team at CohBar has generated more than 1,000 analogs to assess as possible leads for potential development as druggable compounds. “We take those mitochondrial-encoded peptides, synthesize them, and test them using in vitro assays to determine their function. Then we create analogs and perform additional tests including efficacy in animal models of disease to hone those functions and develop enhanced molecules,” Engle said. “We’re not trying to fix the mitochondria,” he stressed. Instead, CohBar is using mitochondria as a source of new medicines, creating compounds that can be injected into the bloodstream to treat acute or chronic diseases. Why does this mitochondrial dysfunction exist? As Engle elaborated, “In the cellular genome, there is an error correcting system. In the mitochondria, this system is much less robust.” “The mitochondria generate ATP and, in the process, they also generate reactive oxygen species that can have deleterious effects on the mitochondria genome.” This deterioration can also reduce the production of mitochondrial peptides, potentially contributing to aging and its associated diseases. Throughout the industry, Engle said, drug development is shifting its focus from organs to cells. As that occurs, researchers are seeing that “the mitochondria affect a large number of systems in multiple ways. Yet, some are still surprised at how one organelle can have so many different effects.” Increasingly, researchers realize that addressing mitochondrial dysfunction may play an important role in increasing “healthspan” – not extending lifespan, but extending the time during which a person is healthy and can live a productive life. “Interest in mitochondria focused drug development is rising and moving beyond scientific conferences into the investor conferences”, Engle noted. “It may take center stage as therapeutic solutions are approved in the future. For now, though, CohBar is focused on the studies needed to advance compounds into the clinic and is anticipating announcing Phase Ib results for CB4211 when they become available. “Next year, we hope to have multiple clinical studies moving along at the same time based on our development activities.” Most Read Today