News in Brief
Authors: Bianca Brandon
Journal: The Lancet Healthy Longevity (2021)

Reactive astrocytes induce cell death via saturated lipidsAstrocytes regulate the CNS’ response to infection and injury but are also implicated in pathological cell death in neurodegenerative disease. The mechanism for inducing cell death remains unknown. Kevin A Guttenplan (Stanford University, Stanford, CA, USA) and colleagues isolated a component of the astrocyte-derived toxic factor. They compared reactive and quiescent astrocytes and the astrocyte conditioned medium (ACM) and found that 176 of 3660 detected proteins secreted by astrocytes changed in quantity when astrocytes became reactive. Large quantities of apolipoprotein E (APOE) and apolipoprotein J (APOJ) were seen in reactive ACM compared to quiescent ACM, suggesting that these lipoproteins are necessary for astrocyte-mediated toxicity. They assessed whether APOE or APOJ were toxic using ACM from APOE and APOJ knock-out mice. Toxic activity in the ACM was unaltered between knock outs and controls, suggesting that the lipoproteins themselves were not toxic. However, in reactive compared with quiescent ACM, they found upregulation of phosphatidylcholines with very-long-chain fatty acid acyl chains (VLCPCs) and saturated long-chain free fatty acids. This finding suggested that saturated long-chain free fatty acids and VLCPCs could mediate toxicity. Ongoing investigation will aim to identify the many signalling pathways mediated by lipids in the CNS, and examine the therapeutic potential of inhibiting these processes in neurodegenerative disease and injury.Ageing and the duodenal microbiomeFor the estimated 3·8 × 1013 microorganisms that have co-evolved with humans as their host, the gut has the largest abundance and diversity. The gut microbiome is known to be involved in metabolism, physiology, and immunity and is also associated with diseases of ageing, including type 2 diabetes, coronary heart disease, Alzheimer's disease, and Parkinson's disease. Gabriela Leite (Cedars-Sinai Medical Center, Los Angeles, CA, USA) and colleagues used validated sampling and processing techniques to characterise changes in the duodenal microbiome with increasing age. 251 participants in four age categories (18–35, 36–50, 51–65, and 66–80 years) were included. As increasing age is associated with the use of an increased number of medications and a higher prevalence of disease, the authors controlled for these factors with multivariate analyses. They saw a decrease in duodenal microbial diversity as a result of a combination of the three factors, rather than age alone. When controlling for chronological age, number of medications used, and number of concomitant diseases, the increased relative abundance of Escherichia, Lactobacillus, and Enterococcus were associated with chronological age only, Klebsiella was associated with number of medications only, and Clostridium and Bilophila were associated with number of concomitant diseases only. Culture findings showed that the decrease in microbial diversity in the duodenum was also associated with a greater abundance of coliform bacteria in older participants (p=0·022). The findings suggest that altered small intestinal microbial populations could also contribute to age-associated diseases. Further studies are needed to understand the causes and implications of these microbial changes with advancing age.Updated advice against aspirin for primary cardiovascular disease preventionAspirin is the most commonly prescribed antiplatelet therapy. In secondary prevention of ischaemia in patients with established cardiovascular disease, use of aspirin is well supported; however, its use in primary prevention is disputed. According to new draft guidelines published in October, 2021, The US Preventive Services Task Force (USPSTF) will no longer recommend routine use of low-dose aspirin in the primary prevention of cardiovascular disease for patients aged 60 years and older, incorporating new evidence in an update to the 2016 guidelines. They also recommended that the decision to initiate low-dose aspirin for the primary prevention of cardiovascular disease in adults aged 40–59 years who have a 10% or greater 10-year risk of cardiovascular disease should be an individual one. The supporting evidence included systematic reviews and a microsimulation modelling study. To evaluate the benefits of aspirin for primary prevention of cardiovascular morbidity and mortality, the task force systematically reviewed 13 randomised clinical trials including 161 680 participants. Although there was a decreased risk of cardiovascular disease, aspirin use did not affect cardiovascular mortality or all-cause mortality overall. In assessment of the harms of aspirin for primary prevention of cardiovascular disease, the task force pooled the results of 14 randomised clinical trials that reported on bleeding events associated with aspirin use. It was shown that the modest benefits of aspirin were outweighed by the risks of bleeding. Other major bodies have already published equivalent advice. The USPSTF stated that more research is needed in gastrointestinal bleeding risk, differences between racial or ethnic and socioeconomic groups, patient preferences, and the effects of low-dose aspirin on colorectal cancer risk. Reactive astrocytes induce cell death via saturated lipidsAstrocytes regulate the CNS’ response to infection and injury but are also implicated in pathological cell death in neurodegenerative disease. The mechanism for inducing cell death remains unknown. Kevin A Guttenplan (Stanford University, Stanford, CA, USA) and colleagues isolated a component of the astrocyte-derived toxic factor. They compared reactive and quiescent astrocytes and the astrocyte conditioned medium (ACM) and found that 176 of 3660 detected proteins secreted by astrocytes changed in quantity when astrocytes became reactive. Large quantities of apolipoprotein E (APOE) and apolipoprotein J (APOJ) were seen in reactive ACM compared to quiescent ACM, suggesting that these lipoproteins are necessary for astrocyte-mediated toxicity. They assessed whether APOE or APOJ were toxic using ACM from APOE and APOJ knock-out mice. Toxic activity in the ACM was unaltered between knock outs and controls, suggesting that the lipoproteins themselves were not toxic. However, in reactive compared with quiescent ACM, they found upregulation of phosphatidylcholines with very-long-chain fatty acid acyl chains (VLCPCs) and saturated long-chain free fatty acids. This finding suggested that saturated long-chain free fatty acids and VLCPCs could mediate toxicity. Ongoing investigation will aim to identify the many signalling pathways mediated by lipids in the CNS, and examine the therapeutic potential of inhibiting these processes in neurodegenerative disease and injury. Astrocytes regulate the CNS’ response to infection and injury but are also implicated in pathological cell death in neurodegenerative disease. The mechanism for inducing cell death remains unknown. Kevin A Guttenplan (Stanford University, Stanford, CA, USA) and colleagues isolated a component of the astrocyte-derived toxic factor. They compared reactive and quiescent astrocytes and the astrocyte conditioned medium (ACM) and found that 176 of 3660 detected proteins secreted by astrocytes changed in quantity when astrocytes became reactive. Large quantities of apolipoprotein E (APOE) and apolipoprotein J (APOJ) were seen in reactive ACM compared to quiescent ACM, suggesting that these lipoproteins are necessary for astrocyte-mediated toxicity. They assessed whether APOE or APOJ were toxic using ACM from APOE and APOJ knock-out mice. Toxic activity in the ACM was unaltered between knock outs and controls, suggesting that the lipoproteins themselves were not toxic. However, in reactive compared with quiescent ACM, they found upregulation of phosphatidylcholines with very-long-chain fatty acid acyl chains (VLCPCs) and saturated long-chain free fatty acids. This finding suggested that saturated long-chain free fatty acids and VLCPCs could mediate toxicity. Ongoing investigation will aim to identify the many signalling pathways mediated by lipids in the CNS, and examine the therapeutic potential of inhibiting these processes in neurodegenerative disease and injury. Ageing and the duodenal microbiomeFor the estimated 3·8 × 1013 microorganisms that have co-evolved with humans as their host, the gut has the largest abundance and diversity. The gut microbiome is known to be involved in metabolism, physiology, and immunity and is also associated with diseases of ageing, including type 2 diabetes, coronary heart disease, Alzheimer's disease, and Parkinson's disease. Gabriela Leite (Cedars-Sinai Medical Center, Los Angeles, CA, USA) and colleagues used validated sampling and processing techniques to characterise changes in the duodenal microbiome with increasing age. 251 participants in four age categories (18–35, 36–50, 51–65, and 66–80 years) were included. As increasing age is associated with the use of an increased number of medications and a higher prevalence of disease, the authors controlled for these factors with multivariate analyses. They saw a decrease in duodenal microbial diversity as a result of a combination of the three factors, rather than age alone. When controlling for chronological age, number of medications used, and number of concomitant diseases, the increased relative abundance of Escherichia, Lactobacillus, and Enterococcus were associated with chronological age only, Klebsiella was associated with number of medications only, and Clostridium and Bilophila were associated with number of concomitant diseases only. Culture findings showed that the decrease in microbial diversity in the duodenum was also associated with a greater abundance of coliform bacteria in older participants (p=0·022). The findings suggest that altered small intestinal microbial populations could also contribute to age-associated diseases. Further studies are needed to understand the causes and implications of these microbial changes with advancing age. For the estimated 3·8 × 1013 microorganisms that have co-evolved with humans as their host, the gut has the largest abundance and diversity. The gut microbiome is known to be involved in metabolism, physiology, and immunity and is also associated with diseases of ageing, including type 2 diabetes, coronary heart disease, Alzheimer's disease, and Parkinson's disease. Gabriela Leite (Cedars-Sinai Medical Center, Los Angeles, CA, USA) and colleagues used validated sampling and processing techniques to characterise changes in the duodenal microbiome with increasing age. 251 participants in four age categories (18–35, 36–50, 51–65, and 66–80 years) were included. As increasing age is associated with the use of an increased number of medications and a higher prevalence of disease, the authors controlled for these factors with multivariate analyses. They saw a decrease in duodenal microbial diversity as a result of a combination of the three factors, rather than age alone. When controlling for chronological age, number of medications used, and number of concomitant diseases, the increased relative abundance of Escherichia, Lactobacillus, and Enterococcus were associated with chronological age only, Klebsiella was associated with number of medications only, and Clostridium and Bilophila were associated with number of concomitant diseases only. Culture findings showed that the decrease in microbial diversity in the duodenum was also associated with a greater abundance of coliform bacteria in older participants (p=0·022). The findings suggest that altered small intestinal microbial populations could also contribute to age-associated diseases. Further studies are needed to understand the causes and implications of these microbial changes with advancing age. Updated advice against aspirin for primary cardiovascular disease preventionAspirin is the most commonly prescribed antiplatelet therapy. In secondary prevention of ischaemia in patients with established cardiovascular disease, use of aspirin is well supported; however, its use in primary prevention is disputed. According to new draft guidelines published in October, 2021, The US Preventive Services Task Force (USPSTF) will no longer recommend routine use of low-dose aspirin in the primary prevention of cardiovascular disease for patients aged 60 years and older, incorporating new evidence in an update to the 2016 guidelines. They also recommended that the decision to initiate low-dose aspirin for the primary prevention of cardiovascular disease in adults aged 40–59 years who have a 10% or greater 10-year risk of cardiovascular disease should be an individual one. The supporting evidence included systematic reviews and a microsimulation modelling study. To evaluate the benefits of aspirin for primary prevention of cardiovascular morbidity and mortality, the task force systematically reviewed 13 randomised clinical trials including 161 680 participants. Although there was a decreased risk of cardiovascular disease, aspirin use did not affect cardiovascular mortality or all-cause mortality overall. In assessment of the harms of aspirin for primary prevention of cardiovascular disease, the task force pooled the results of 14 randomised clinical trials that reported on bleeding events associated with aspirin use. It was shown that the modest benefits of aspirin were outweighed by the risks of bleeding. Other major bodies have already published equivalent advice. The USPSTF stated that more research is needed in gastrointestinal bleeding risk, differences between racial or ethnic and socioeconomic groups, patient preferences, and the effects of low-dose aspirin on colorectal cancer risk. Aspirin is the most commonly prescribed antiplatelet therapy. In secondary prevention of ischaemia in patients with established cardiovascular disease, use of aspirin is well supported; however, its use in primary prevention is disputed. According to new draft guidelines published in October, 2021, The US Preventive Services Task Force (USPSTF) will no longer recommend routine use of low-dose aspirin in the primary prevention of cardiovascular disease for patients aged 60 years and older, incorporating new evidence in an update to the 2016 guidelines. They also recommended that the decision to initiate low-dose aspirin for the primary prevention of cardiovascular disease in adults aged 40–59 years who have a 10% or greater 10-year risk of cardiovascular disease should be an individual one. The supporting evidence included systematic reviews and a microsimulation modelling study. To evaluate the benefits of aspirin for primary prevention of cardiovascular morbidity and mortality, the task force systematically reviewed 13 randomised clinical trials including 161 680 participants. Although there was a decreased risk of cardiovascular disease, aspirin use did not affect cardiovascular mortality or all-cause mortality overall. In assessment of the harms of aspirin for primary prevention of cardiovascular disease, the task force pooled the results of 14 randomised clinical trials that reported on bleeding events associated with aspirin use. It was shown that the modest benefits of aspirin were outweighed by the risks of bleeding. Other major bodies have already published equivalent advice. The USPSTF stated that more research is needed in gastrointestinal bleeding risk, differences between racial or ethnic and socioeconomic groups, patient preferences, and the effects of low-dose aspirin on colorectal cancer risk.