Tag: Aging Research

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The Brain Age Gap

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The Trending With Impact series highlights Aging publications (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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Aging is a risk factor for many diseases, including Alzheimer’s disease (AD). While scientists have made some progress in understanding the physiology of aging and its relationship to AD and related disorders, our understanding remains incomplete (to say the least). It is possible that civilization is currently in the midst of an artificial intelligence (AI) and machine learning (ML) “boom.” Researchers are now using AI and ML technologies to elevate our comprehension of aging and aging-related diseases.

“Artificial intelligence (AI) and machine learning (ML) technologies can help us better understand these diseases and aging itself by using biological data from the brain or other sources to create a mapping between age and biological data.”

In a new editorial paper, researchers Jeyeon Lee, Leland R. Barnard and David T. Jones from the Mayo Clinic in Rochester, Minnesota, discuss a recent study they conducted and explore the potential of AI to revolutionize the field of geriatrics. Their editorial was published in Aging’s Volume 15, Issue 8, on April 3, 2023, entitled, “Artificial intelligence and the aging mind.”

Their Study

In a recent 2022 study, Lee, Barnard, Jones, and the rest of their team developed convolutional neural network-based brain age prediction models using a large collection of data from brain magnetic resonance imaging (MRI) and brain fluorodeoxyglucose positron-emission tomography (FDG-PET) in people aged from 26 to 98 years old. In a sample of cognitively normal individuals, the AI models showed accurate brain age estimation of which a mean absolute error (MAE; unit, years) was 3.08±0.14 for the FDG-based model and 3.49±0.16 for the MRI-based model. 

The team found that higher brain age gaps (the difference between biological age and chronological age) were estimated in cohorts with neurodegenerative disorders—including mild cognitive impairment (MCI), AD, frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB)—than normal controls. The brain age gap was strongly associated with pathologic tau protein levels and cognitive test scores. This gap also showed longitudinal predictive ability for cognitive decline in AD-related disorders.

“Interestingly, the brain imaging patterns generating brain age gaps in AD showed higher similarity with normal aging than other neurodegenerative syndromes implying that AD might be more like an accelerated representation of biological aging than others.”

Summary & Conclusions

The study conducted by Lee, Barnard, Jones, and their team using neural network-based brain age prediction models has shown promising results in accurately estimating brain age and identifying differences between normal aging and neurodegenerative disorders. However, the authors of this editorial note that variations in data make creating a uniform language used to compare and contrast large sums of data very difficult.

“Although more research and optimization are needed to determine its clinical usefulness, the study of brain age has great potential as a tool for understanding brain aging and age-related diseases.”

In conclusion, aging is a complex process that increases the risk of Alzheimer’s disease and various diseases. Recent advancements in artificial intelligence and machine learning technologies offer new opportunities to better understand the underlying mechanisms of aging and aging-related disorders. This research opens up exciting possibilities for the future of geriatric care and improving the lives of aging populations. As technology continues to advance, it is likely that we will gain further insights into aging through the brain age gap, ultimately leading to better prevention, diagnosis and treatment options.

“The fact that the brain age gap is a comprehensive and intuitive measure of disease severity using biological data that is already being acquired in clinical practice, makes it an attractive biomarker for further development for clinical use [8].”

Click here to read the full editorial paper published by Aging.

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Aging is an open-access, peer-reviewed journal that has been publishing high-impact papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

Click here to subscribe to Aging publication updates.

For media inquiries, please contact [email protected].

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High School Students Use AI to Make Aging and Glioblastoma Discoveries

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In a breakthrough study, three high school students and Insilico researchers used generative artificial intelligence (AI) to help identify new therapeutic targets for glioblastoma multiforme (GBM) and aging.

High School Students Use AI to Make Aging and Glioblastoma Discoveries
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Glioblastoma multiforme (GBM) is one of the most aggressive and fatal malignant brain tumors. With a median survival time of 15 months, only about 25% of patients survive for one year and less than 5% survive for five years. As people get older, the risk of developing GBM increases. The discovery of new drug targets for GBM is of paramount importance.

The good news here is that high school students, Zachary Harpaz, Andrea Olsen and Christopher Ren, and researchers Anastasia Shneyderman, Alexander Veviorskiy, Maria Dralkina, Simon Konnov, Olga Shcheglova, Frank W. Pun, Geoffrey Ho Duen Leung, Hoi Wing Leung, Ivan V. Ozerov, Alex Aliper, Mikhail Korzinkin, and Alex Zhavoronkov have recently made remarkable strides in the joint field of aging and glioblastoma research. The team used a generative artificial intelligence (AI) engine from Insilico Medicine (founded by Dr. Alex Zhavoronkov) called PandaOmics, to identify new therapeutic targets for both GBM and aging. On April 26, 2023, their research paper was published in Aging’s Volume 15, Issue 8, entitled, “Identification of dual-purpose therapeutic targets implicated in aging and glioblastoma multiforme using PandaOmics – an AI-enabled biological target discovery platform.”

Their Study

Andrea Olsen, a student at Sevenoaks School in Kent, UK, and CEO/co-founder of The Youth Longevity Association
Photo of Andrea Olsen, courtesy of Insilico Medicine

“[Glioblastoma multiforme] is one of the most horrible cancers because it has such a short survival time,” Andrea Olsen said. “Of course, it affects the brain and so affects the body because the brain is the control center of the entire body.”

Andrea Olsen, a student at Sevenoaks School in Kent, UK, and CEO/co-founder of The Youth Longevity Association, discovered her interest in neurobiology and technology while growing up in Oslo, Norway. In 2021, she started an internship at Insilico Medicine. Through her work with the researchers at Insilico Medicine, Olsen learned how to use AI to uncover new genetic targets that could be used to treat aging and cancer. Zachary Harpaz, a student at Pine Crest School in Fort Lauderdale, Florida, discovered his passion for biology after being introduced to the subject in 2020. He combined his passion for biology with his intrigue for computer science and AI to enter the field of aging research.

Zachary Harpaz, a student at Pine Crest School in Fort Lauderdale, Florida
Photo of Zachary Harpaz, courtesy of Insilico Medicine

“We wanted to find new putative targets for glioblastoma as well as aging—attacking them both at the same time,” explained Harpaz.

The researchers used a comprehensive approach to identify their targets. They split their data into three categories—young, middle-aged and senior—and mapped the importance of gene expression to survival. They analyzed 12 datasets and selected the genes that were overlapped in 11 of the 12 datasets. They also cross-referenced those genes with a recent study conducted by the researchers at Insilico Medicine in 2022 on putative targets for aging and certain diseases. 

PandaOmics

One of the most exciting aspects of their research was the use of PandaOmics. Typically, finding new drugs requires experts to comb through a myriad of data and conduct extensive research. With PandaOmics, AI quickly processes and analyzes the data to identify new therapeutic targets, reducing the time and resources required for drug development. These high school researchers used PandaOmics to screen datasets from the Gene Expression Omnibus repository (maintained by the National Center for Biotechnology Information) and discovered three new potential therapeutic targets for treating both aging and GBM.

The first target for glioblastoma and aging was CNGA3, which they selected after analyzing each gene through PandaOmics. They also analyzed negatively correlated genes and selected GLUD1 as the number one gene produced by PandaOmics. Finally, they cross-referenced genes highly correlated to aging with the previous 2022 study and selected SIRT1 as another potential therapeutic target. The students were excited by the findings. Before she interned with Insilico, Olsen said she didn’t realize that AI could be so helpful in finding completely new therapeutic targets. 

“For me, [working with Insilico] was an incredible opportunity to dive into the field of research, aging, longevity, and neuroscience. It really kick-started my entire career,” Olsen said.

Looking Ahead

Overall, the study conducted by the researchers and these high school students showcases the power of AI in drug discovery and highlights the potential for young researchers to make meaningful contributions to the field. Their findings could lead to the development of new therapies for glioblastoma and aging-related diseases. Other therapeutics identified through Insilico’s Pharma.AI platform—specifically for idiopathic pulmonary fibrosis and COVID-19—have already advanced to human clinical trials.

“I’m excited to continue my research into college, but I’m super grateful for this opportunity at Insilico. It allowed me to get a head start on learning how to conduct research, analyze data and use the coolest and most cutting edge AI in the drug development area,” Harpaz said. “That experience gave me an amazing head start and I’m super excited to continue that into college, and even after college.”

Click here to read the full research paper published by Aging.

AGING (AGING-US) VIDEOS: YouTube | LabTube | Aging-US.com

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Aging is an open-access, peer-reviewed journal that has been publishing high-impact papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

Click here to subscribe to Aging publication updates.

For media inquiries, please contact [email protected].

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RNA Virus Fruit Fly Model: First Study to Measure Single-Fly Respiration

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In a new study, researchers investigated the mortality and respiration rates of RNA virus-infected male fruit flies and how aging impacts these outcomes and measurements.

RNA Virus Fruit Fly Model: First Study to Measure Single-Fly Respiration

RNA viruses are responsible for approximately 70% of emerging infectious diseases in humans, according to a 2020 report by the National Academy of Medicine. Examples of RNA viruses include: influenza, hepatitis C, HIV, measles, zika, ebola, poliovirus, rhinovirus, rabies, and SARS-CoV-2—the virus responsible for the COVID-19 pandemic. After infection with an RNA virus, significant changes can take place in the host’s metabolism. While it is clear that disease tolerance declines as humans age, it is not yet clear how aging affects virus-induced changes in metabolism.

“Virus-induced metabolic reprogramming could impact infection outcomes, however, how this is affected by aging and impacts organismal survival remains poorly understood.”

In a new study, researchers Eli Hagedorn, Dean Bunnell, Beate Henschel, Daniel L. Smith Jr., Stephanie Dickinson, Andrew W. Brown, Maria De Luca, Ashley N. Turner, and Stanislava Chtarbanova from the University of Alabama, Indiana University, University of Arkansas for Medical Sciences, Arkansas Children’s Research Institute, and Jacksonville State University examined how an RNA virus can affect the respiration rate in male fruit flies (Drosophila melanogaster), both young and old. On March 22, 2023, their research paper was published in Aging’s Volume 15, Issue 6, entitled, “RNA virus-mediated changes in organismal oxygen consumption rate in young and old Drosophila melanogaster males.”

The Study

An organism’s metabolism depends on oxygen to produce energy. An efficient immune system depends, in part, on energy from the body’s metabolism to fuel it. Paradoxically, decreased metabolism, or hypometabolism, is a survival strategy that promotes disease tolerance in response to infection. In this study, the researchers used oxygen consumption rate (OCR) to indirectly measure changes in metabolism before and after RNA viral infection. The team infected male fruit flies with the RNA virus Flock House virus (FHV), and documented their oxygen consumption rate and/or mortality times at different time intervals after infection.

“As the exact mechanisms by which hypometabolism promotes tolerance are not fully understood, D. melanogaster could serve as an excellent model to dissect the genetic and molecular bases of this process.”

After the first 72-hours post-infection, FHV appeared to modulate respiration in all flies, but age did not appear to have a significant effect on OCR. However, over the course of the three-day experiment, the longitudinal assessment showed that OCR in young flies progressively and significantly decreased, while OCR in aged flies remained constant. The researchers found that the OCR at 24-hours varied in response to both experimental treatment and survival status. FHV-injected flies that died prior to 48- or 72-hours had a lower OCR compared to survivors at 48-hours. 

“Our results show that FHV infection significantly reduces organismal OCR compared to Tris-injected controls; however, we did not observe a significant change in OCR with aging. Interestingly, flies that died prior to 48-hours post-treatment measurements exhibited a significantly lower OCR at 24 h post-treatment compared to survivors. These findings suggest that the host’s metabolic profile could influence the outcome of viral infections.”

Conclusion

In conclusion, RNA viruses pose a significant threat to human health, causing numerous emerging infectious diseases. The impact of these viruses on the host’s metabolism, particularly in relation to aging, remains poorly understood. The recent study by Hagedorn et al. sheds light on the interaction between RNA viruses, metabolism and aging by examining the effects of the Flock House virus on the respiration rate of male fruit flies. The findings suggest that this infection can modulate the host’s OCR, and that the metabolic profile of the host could influence the outcome of viral infections.  The authors suggest that further research is needed to determine the precise mechanisms by which RNA viruses affect metabolic rate and to explore the potential for interventions to modulate metabolic rate and improve healthspan and lifespan.

“Older flies exhibit impaired disease tolerance to FHV [19], and here we show that metabolic rate depression does not occur in older flies in response to FHV in the first three days following treatment. It is therefore possible that as is the case in mammals, flies employ hypometabolism as a survival strategy that is part of a disease tolerance mechanism. It would be interesting in the future to test this hypothesis by comparing OCR in tolerance mutant flies such as the G9a mutants.”

Click here to read the full research paper published by Aging.

AGING (AGING-US) VIDEOS: YouTube | LabTube | Aging-US.com

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Aging is an open-access, peer-reviewed journal that has been publishing high-impact papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

Click here to subscribe to Aging publication updates.

For media inquiries, please contact [email protected].

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A Promising Approach to Preventing Periodontitis

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A new study by researchers from Osaka University’s Graduate School of Dentistry investigated cellular senescence in periodontal tissue and disease—identifying promising therapeutic targets for preventing periodontitis in the elderly.

A new study by researchers from Osaka University’s Graduate School of Dentistry investigated cellular senescence in periodontal tissue and disease—identifying promising therapeutic targets for preventing periodontitis in the elderly.

The Trending With Impact series highlights Aging publications (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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Repercussions of poor dental health aren’t limited to mere social stigmas. Poor dental health can impart serious consequences on an individual’s overall health. Periodontal disease broadly refers to any disease that affects the gums and the surrounding tissues that support the teeth, including the periodontal ligament (PDL) and alveolar bone. Periodontal disease can increase the risk of heart disease, stroke and diabetes by allowing bacteria to enter the bloodstream, causing inflammation and organ damage. 

Periodontitis is a more advanced stage of periodontal disease. It is thought to be the most common infectious disease in the United States—affecting more than 40% of adults over 30 years old. Previous research has suggested that aging is a significant risk factor for periodontitis, although the underlying mechanisms are unclear.

“The direct cause of periodontitis is periodontopathic bacteria, while various environmental factors affect the severity of periodontitis. Previous epidemiological studies have shown positive correlations between aging and periodontitis. However, whether and how aging is linked to periodontal health and disease in biological processes is poorly understood.”

In a recent study, researchers Kuniko Ikegami, Motozo Yamashita, Mio Suzuki, Tomomi Nakamura, Koki Hashimoto, Jirouta Kitagaki, Manabu Yanagita, Masahiro Kitamura, and Shinya Murakami from Osaka University’s Graduate School of Dentistry aimed to elucidate the underlying mechanisms that contribute to aging-associated inflammation in periodontitis. On March 1, 2023, their new research paper was published in Aging (Aging-US) Volume 15, Issue 5, entitled, “Cellular senescence with SASP in periodontal ligament cells triggers inflammation in aging periodontal tissue.”

The Study

“In this study, we aimed to clarify the pathophysiological roles of cellular senescence in periodontal tissue and diseases.”

Previous studies have found that senescent cells can secrete senescence-associated secretory proteins (SASP) that induce inflammation and impair wound healing in some chronic diseases. The existence of senescent cells in periodontal tissue and diseases, however, has yet to be clarified. In this study, the researchers investigated cellular senescence and SASP in aging periodontal tissue. The team aimed to uncover the mechanism by which cellular senescence and SASP trigger inflammation in periodontal tissue and to identify potential therapeutic targets for this disease. 

To investigate the role of cellular senescence in periodontitis, the researchers analyzed periodontal tissue in young and aged mice. Alveolar bone volume was compared in the young and aged mice, and beta-galactosidase (β-gal) staining was performed. They found bone resorption in aged mice and many senescence-associated (SA) β-gal-positive cells in their periodontal tissue, leading to inflammation and breakdown of alveolar bone. Very few SA β-gal-positive cells were found in young mouse tissues.

Next, the researchers worked with cells in vitro, primary human periodontal ligament (HPDL) cells, and induced cellular senescence through serial passaging (replicative senescence). The growth rate of HPDL cells gradually reduced, and they reached irreversible cell growth arrest, indicating the induction of cellular senescence. Morphological changes were observed through phalloidin staining. The team found that around 70% of aged HPDL cells were positive for SA β-gal, while less than 10% of young HPDL cells were positive. Morphological changes showed that aged HPDL cells had an enlarged and “spread” cell shape compared to young HPDL cells. Flow cytometry analysis confirmed an increase in cell size and granularity of aged HPDL cells compared to young HPDL cells.

TEM analysis showed that senescent cells exhibit metabolic changes and irregularly shaped mitochondria with disrupted cristae and increased accumulation of ROS, which suggest damage and failure of the redox balance. Importantly, the researchers found that the intrinsic inflammation state of aged PDLs was higher than in young PDLs, and susceptibility to bactericidal pathogens (but not inflammatory cytokines) was low in aged PDLs. Additionally, the team observed an age-dependent upregulation of microRNA (miR)-34a in HPDL cells.

“Thus, miR-34a and senescent PDL cells might be promising therapeutic targets for periodontitis in elderly people.”

Summary & Conclusion

In conclusion, poor dental health can have serious implications on an individual’s overall health, as periodontal disease can increase the risk of heart disease, stroke and diabetes. Aging is a significant risk factor for periodontitis, which is thought to be the most common infectious disease in the United States. A recent study by researchers from Osaka University’s Graduate School of Dentistry aimed to elucidate the underlying mechanisms that contribute to aging-associated inflammation in periodontitis. The study found that senescent cells in periodontal tissue secrete SASP that induce inflammation. The researchers identified potential therapeutic targets for periodontitis and suggest that elimination of senescent PDL cells or suppression of the miR-34a-dependent SIRT1-NF-κB axis may be an attractive therapeutic strategy to prevent periodontitis in humans as we age.

“To the best of our knowledge, this is the first study to identify: 1) the potential for senescent PDL cells to induce inflammation of periodontal tissue, and 2) a miRNA-dependent molecular mechanism of SASP in senescent PDL cells.”

Click here to read the full research paper published by Aging.

AGING (AGING-US) VIDEOS: YouTube | LabTube | Aging-US.com

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Aging is an open-access, peer-reviewed journal that has been publishing high-impact papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

Click here to subscribe to Aging publication updates.

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Fruit Flies Shed New Light on Memory and Aging

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In a recent study, researchers from Western University and Indiana University investigated the connection between aging, memory and lactate metabolism in flies.

Fruit Flies Shed New Light on Memory and Aging
Male common fruit fly (Drosophila Melanogaster) doing what fruit flies do best – enjoing its fruit (apple)

The Trending With Impact series highlights Aging publications (listed by MEDLINE/PubMed as “Aging (Albany NY)” and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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The brain is a complex organ responsible for many critical functions, including the formation and retrieval of our memories. As we age, the brain undergoes changes that can affect cognitive abilities, including our memory. Understanding the mechanisms that underlie these changes is critical for developing therapies for age-related cognitive decline. 

“Over the last two decades there has been growing recognition that lactate, the end product of glycolysis, serves many functions, including acting as a source of energy, a signaling molecule, and even as an epigenetic regulator.”

Lactate & LDH

Lactate is a molecule that is produced during the metabolism of glucose in the body. It is a byproduct of anaerobic metabolism, which occurs when there is insufficient oxygen supply to meet the energy demands of the body. Lactate can be used as an energy source by some cells, such as the heart and skeletal muscles, and it can also be transported to the liver where it can be converted back into glucose.

Lactate dehydrogenase (LDH), on the other hand, is an enzyme that catalyzes the conversion of pyruvate to lactate (the reverse reaction of lactate production) and is also involved in other metabolic processes. This enzyme is found in many tissues of the body, including the heart, liver and skeletal muscles, and is released into the bloodstream when tissues are damaged. LDH is often used as a diagnostic marker for various medical conditions, such as heart attacks, liver disease and certain cancers. High levels of LDH in the blood may indicate tissue damage or cell death, while low levels may indicate a deficiency in the enzyme.

The Study

Recently, researchers investigated the role of LDH in memory formation and aging using Drosophila melanogaster (fruit flies) as a model organism. In a new study, researchers Ariel K. Frame, J. Wesley Robinson, Nader H. Mahmoudzadeh, Jason M. Tennessen, Anne F. Simon, and Robert C. Cumming from Western University and Indiana University used genetic manipulation techniques to alter LDH expression in the neurons or glia of fruit flies to investigate its effects on aging and memory. Their research paper was published in Aging’s Volume 15, Issue 4, and entitled, “Aging and memory are altered by genetically manipulating lactate dehydrogenase in the neurons or glia of flies.”

“The astrocyte-neuron lactate shuttle hypothesis posits that glial-generated lactate is transported to neurons to fuel metabolic processes required for long-term memory.”

Lactate shuttling is a process in which lactate is transported from one cell or tissue to another for use as an energy source or as a signaling molecule. Previous research has shown that LDH is expressed in both neurons and glia in the brain, and that it may play a role in regulating synaptic plasticity and memory formation. The authors of the current research paper aimed to test the hypothesis that alterations in LDH expression in the brain may contribute to age-related cognitive decline.

“D. melanogaster serves as a good model for understanding the role of glia-neuron lactate shuttling in central nervous system (CNS) function and cognitive behaviour.”

To test this hypothesis, the researchers genetically manipulated LDH expression in the neurons or glia of fruit flies (dLDH) and assessed the impact on memory formation and aging. Specifically, they used RNA interference (RNAi) to either knock down or overexpress dLDH in either neurons or glia. They then assessed the effects of these manipulations on two different memory tasks at different ages, courtship memory and aversive olfactory memory, and also assessed survival, negative geotaxis, brain neutral lipids (the core component of lipid droplets), and brain metabolites.

Results

Their results showed that dLDH manipulation had differential effects on fruit flies depending on the cell type in which it was altered. In neurons, both upregulation and downregulation of dLDH resulted in memory impairment and decreased survival with age. In contrast, downregulation of dLDH in glial cells caused age-related memory impairment, without altering survival. Upregulating dLDH expression in glial cells lowered survival without disrupting memory. Both neuronal and glial dLDH upregulation increased neutral lipid accumulation.

“We provide evidence that altered lactate metabolism with age affects the tricarboxylic acid (TCA) cycle, 2-hydroxyglutarate (2HG), and neutral lipid accumulation.”

The results of this study may provide new insights into the role of LDH in memory formation and aging in humans. The findings suggest that LDH may be a potential target for developing therapies to combat age-related cognitive decline. Additionally, the study highlights the importance of considering cell-type specificity when investigating the role of genes and enzymes in complex biological processes. A limitation of the study is that it was conducted in fruit flies, which may not fully capture the complexity of memory formation and aging in humans. However, fruit flies have been shown to be a valuable model organism for studying many aspects of brain function, and the findings of this study may provide a foundation for future research in mammals.

“Collectively, our findings indicate that the direct alteration of lactate metabolism in either glia or neurons affects memory and survival but only in an age-dependent manner.”

Conclusion

In conclusion, the study provides new insights into the role of LDH in memory formation and aging. The findings suggest that LDH may play a critical role in regulating energy metabolism in the brain, which in turn affects synaptic plasticity and memory formation. The study also highlights the importance of considering cell-type specificity when investigating the role of genes and enzymes in complex biological processes. Future research in mammals may be needed to further explore the implications of these findings for human health and the potential for developing therapies for age-related cognitive decline. Nonetheless, this study provides an important step forward in understanding the complex interplay between lactate metabolism, memory and aging.

“In this study we demonstrate the importance of maintaining appropriate levels of dLdh in D. melanogaster glia and neurons for maintenance of long-term courtship memory and survival with age (Figure 6). In addition, our results implicate lipid metabolism, 2HG accumulation, and changes in TCA cycle activity as factors underlying the age-related impacts of perturbed dLdh expression, which likely modifies glia-neuron lactate shuttling in the fly brain.”

Click here to read the full research paper published by Aging.

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Aging is an open-access, peer-reviewed journal that has been publishing high-impact papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

For media inquiries, please contact [email protected].

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The Role of Lipids in Aging: Insights From C. Elegans

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In a new study, researchers used C. elegans to investigate how changes in lipids during aging might impact lifespan and healthspan.

The Role of Lipids in Aging: Insights From C. Elegans

The Trending With Impact series highlights Aging publications (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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Listen to an audio version of this article

Lipids are a diverse group of biomolecules that are essential for life, including fats, oils, waxes, and steroids, and play crucial roles in cell membrane structure, energy storage and signaling. Lipidomics is the comprehensive analysis of lipids and their interactions in biological systems, with an aim to understand the role of lipids in cellular processes and their association with diseases. As we age, our cells undergo complex changes, including alterations in cellular lipid profiles. These changes are not only confined to humans; organisms such as the nematode Caenorhabditis elegans (C. elegans) are also subject to changes in lipid composition during aging. 

“For example, lipid classes including fatty acids (FA), triacylglycerols (TAG), sphingolipids (SL), and phospholipids (PL) have been identified as targets in lipid signatures related to aging [2, 3]. Furthermore, specific signatures are detected in the lipid profiles of those with age-related diseases, such as Alzheimer’s Disease [4–9]. In addition, the abundance of many fatty acid subtypes differs between the youth, elderly, and centenarians [10, 11].”

In a recent study, researchers Trisha A. Staab, Grace McIntyre, Lu Wang, Joycelyn Radeny, Lisa Bettcher, Melissa Guillen, Margaret P. Peck, Azia P. Kalil, Samantha P. Bromley, Daniel Raftery, and Jason P. Chan from Marian University, the University of Washington and Juniata College investigate the lipid profiles of C. elegans with mutations in the genes asm-3/acid sphingomyelinase and hyl-2/ceramide synthase during aging. On February 13, 2023, their research paper was published in Aging’s Volume 15, Issue 3, entitled, “The lipidomes of C. elegans with mutations in asm-3/acid sphingomyelinase and hyl-2/ceramide synthase show distinct lipid profiles during aging.”

The Study

In this study, the researchers focused on two enzymes that are important in the production of ceramides—a type of lipid that is known to play a role in various cellular processes, including cell signaling and apoptosis. The enzymes, acid sphingomyelinase 3 (asm-3) and ceramide synthase (Hyl-2), are involved in the breakdown of sphingomyelin and the synthesis of ceramide, respectively. The team compared C. elegans with mutations in these specific genes with wild type C. elegans at one-, five- and 10-days of age to investigate how changes in these enzymes affect lipid profiles during aging.

“In particular, work using C. elegans have identified age related changes in specific lipids, lipid classes, as well as the ratio of monosaturated to polysaturated fatty acids (MUFA:PUFA ratio) [36, 37]. Here, we examine the lipidomes of animals lacking the sphingolipid metabolism enzymes, asm-3/acid sphingomyelinase or hyl-2/ceramide synthase, which have previously been shown to have extended and reduced lifespans, respectively, in C. elegans [24, 34, 38].”

The results showed that the asm-3 mutant worms had higher levels of sphingomyelin and lower levels of ceramides compared to wild-type worms. In contrast, the hyl-2 mutant worms had lower levels of sphingomyelin and higher levels of ceramides. These findings suggest that asm-3 and Hyl-2 have opposite effects on the production of ceramides in C. elegans. The researchers also found that the lipid profiles of the mutant worms changed with age, with a decrease in sphingomyelin and an increase in ceramides in the asm-3 mutant worms and, in the hyl-2 mutant worms, there was an increase in sphingomyelin and a decrease in ceramides with age.

The researchers also investigated the effects of these lipid profile changes on lifespan and healthspan. They found that the asm-3 mutant worms had a shorter lifespan and reduced healthspan compared to wild-type worms. In contrast, the hyl-2 mutant worms had an extended lifespan and improved healthspan. These findings suggest that changes in lipid profiles can have significant effects on lifespan and healthspan in C. elegans.

Conclusions

Overall, this study sheds light on the complex role of lipids in aging and highlights the importance of ceramides in cellular processes. The findings suggest that changes in the production of ceramides, mediated by asm-3 and Hyl-2, can have significant effects on lifespan and healthspan in C. elegans. Further research in this area could lead to the development of interventions that target ceramide production to promote healthy aging in humans.

There are several potential implications of this study for human health. First, the findings suggest that interventions aimed at modulating ceramide production could have significant effects on aging-related diseases. Ceramide has been implicated in various diseases, including cancer, Alzheimer’s disease and diabetes. Targeting ceramide production could be a promising strategy for the prevention and treatment of these diseases.

Second, the study highlights the importance of understanding the complex interplay between lipids and cellular processes in aging. Aging is a complex process that involves multiple cellular and molecular changes, and alterations in lipid metabolism are just one aspect of this process. A better understanding of the role of lipids in aging could lead to the development of new interventions that target multiple aspects of the aging process.

Finally, the study underscores the importance of using model organisms, such as C. elegans, to investigate the molecular mechanisms of aging. While C. elegans is a simple organism, it shares many fundamental biological processes with humans, and its short lifespan makes it an ideal model for aging research. The findings from this study could be applied to future research in humans, as well as other model organisms, and could lead to the development of novel interventions for aging-related diseases.

“Age caused increased sphingomyelin levels, particularly in short-lived animals. This may suggest that the regulation of sphingolipid metabolism may mediate changes in cell structure and function important for healthy aging. Future studies connecting lipidomic changes in sphingolipid metabolism mutants to mechanistic changes in cells of mutant models will be important next steps to better understanding the roles of sphingolipids in aging.”

Click here to read the full research paper published by Aging.

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Aging is an open-access, peer-reviewed journal that has published high-impact research papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

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Aging’s Top 10 Papers in 2022 (Crossref Data)

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Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Aging (Aging-US) papers based on the number of times a DOI is successfully resolved. Below are Crossref’s Top 10 Aging DOIs in 2022.

Read Crossref’s Top 10 Aging DOIs in 2022.

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#10: DNA- and telomere-damage does not limit lifespan: evidence from rapamycin

DOI: https://doi.org/10.18632/aging.202674

Author: Mikhail V. Blagosklonny

Institution: Roswell Park Cancer Institute

Quote: “Failure of rapamycin to extend lifespan in DNA repair mutant and telomerase-knockout mice, while extending lifespan in normal mice, indicates that neither DNA damage nor telomere shortening limits normal lifespan or causes normal aging.”

#9: Psychological factors substantially contribute to biological aging: evidence from the aging rate in Chinese older adults

DOI: https://doi.org/10.18632/aging.204264

Authors: Fedor Galkin, Kirill Kochetov, Diana Koldasbayeva, Manuel Faria, Helene H. Fung, Amber X. Chen, and Alex Zhavoronkov

Institutions: Deep Longevity Limited, Stanford University, The Chinese University of Hong Kong, Insilico Medicine, and Buck Institute for Research on Aging

Quote: “We have developed a deep learning aging clock using blood test data from the China Health and Retirement Longitudinal Study, which has a mean absolute error of 5.68 years. We used the aging clock to demonstrate the connection between the physical and psychological aspects of aging. The clock detects accelerated aging in people with heart, liver, and lung conditions.”

#8: DNA methylation GrimAge strongly predicts lifespan and healthspan

DOI: https://doi.org/10.18632/aging.101684

Authors: Ake T. Lu, Austin Quach, James G. Wilson, Alex P. Reiner, Abraham Aviv, Kenneth Raj, Lifang Hou, Andrea A. Baccarelli, Yun Li, James D. Stewart, Eric A. Whitsel, Themistocles L. Assimes, Luigi Ferrucci, and Steve Horvath

Institutions: University of California Los Angeles, University of Mississippi Medical Center, Fred Hutchinson Cancer Research Center, Rutgers State University of New Jersey, Public Health England, Northwestern University Feinberg School of Medicine, Columbia University Mailman School of Public Health, University of North Carolina, Chapel Hill, Stanford University School of Medicine, VA Palo Alto Health Care System, and National Institutes of Health

Quote: “We coin this DNAm-based biomarker of mortality “DNAm GrimAge” because high values are grim news, with regards to mortality/morbidity risk. Our comprehensive studies demonstrate that DNAm GrimAge stands out when it comes to associations with age-related conditions, clinical biomarkers, and computed tomography data.”

#7: Hallmarks of aging-based dual-purpose disease and age-associated targets predicted using PandaOmics AI-powered discovery engine

DOI: https://doi.org/10.18632/aging.203960

Authors: Frank W. Pun, Geoffrey Ho Duen Leung, Hoi Wing Leung, Bonnie Hei Man Liu, Xi Long, Ivan V. Ozerov, Ju Wang, Feng Ren, Alexander Aliper, Evgeny Izumchenko, Alexey Moskalev, João Pedro de Magalhães, and Alex Zhavoronkov

Institutions: Insilico Medicine Hong Kong Ltd., University of Chicago, George Mason University (GMU), University of Liverpool, and Buck Institute for Research on Aging

Quote: “In this study, we used a variety of target identification and prioritization techniques offered by the AI-powered PandaOmics platform, to propose a list of promising novel aging-associated targets that may be used for drug discovery. We also propose a list of more classical targets that may be used for drug repurposing within each hallmark of aging.”

#6: CircRNA_100367 regulated the radiation sensitivity of esophageal squamous cell carcinomas through miR-217/Wnt3 pathway

DOI: https://doi.org/10.18632/aging.102580

Authors: Junqi Liu, Nannan Xue, Yuexin Guo, Kerun Niu, Liang Gao, Song Zhang, Hao Gu, Xin Wang, Di Zhao, and Ruitai Fan

Institutions: The First Affiliated Hospital of Zhengzhou University, German Cancer Research Center (DKFZ) and Saarland University Medical Center

Quote: “Circular RNAs (circRNAs) play important roles in regulating the radioresistance of esophageal squamous cell carcinoma (ESCC). This study aimed to determine the role of hsa_circRNA_100367 in regulating radioresistance of ESCC.”

#5: Five years of exercise intervention at different intensities and development of white matter hyperintensities in community dwelling older adults, a Generation 100 sub-study

DOI: https://doi.org/10.18632/aging.203843

Authors: Anette Arild, Torgil Vangberg, Hanne Nikkels, Stian Lydersen, Ulrik Wisløff, Dorthe Stensvold, and Asta K. Håberg

Institutions: NTNU Norwegian University of Science and Technology, UiT The Arctic University of Norway, University Hospital of North Norway, and Trondheim University Hospital

Quote: “We investigated if a five-year supervised exercise intervention with moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT) versus control; physical activity according to national guidelines, attenuated the growth of white matter hyperintensities (WMH). We hypothesized that supervised exercise, in particular HIIT, reduced WMH growth.”

#4: The aging-related risk signature in colorectal cancer

DOI: https://doi.org/10.18632/aging.202589

Authors: Taohua Yue, Shanwen Chen, Jing Zhu, Shihao Guo, Zhihao Huang, Pengyuan Wang, Shuai Zuo, and Yucun Liu

Institution: Peking University

Quote: “Colorectal cancer (CRC) is the third most common cancer worldwide. The opening of the TCGA and GEO databases has promoted the progress of CRC prognostic assessment, while the aging-related risk signature has never been mentioned. R software packages, GSEA software, Venn diagram, Metascape, STRING, Cytoscape, cBioPortal, TIMER and GeneMANIA website were used in this study.”

#3: An epigenetic biomarker of aging for lifespan and healthspan

DOI: https://doi.org/10.18632/aging.101414

Authors: Morgan E. Levine, Ake T. Lu, Austin Quach, Brian H. Chen, Themistocles L. Assimes, Stefania Bandinelli, Lifang Hou, Andrea A. Baccarelli, James D. Stewart, Yun Li, Eric A. Whitsel, James G Wilson, Alex P Reiner, Abraham Aviv, Kurt Lohman, Yongmei Liu, Luigi Ferrucci, and Steve Horvath

Institutions: University of California Los Angeles, National Institutes of Health, Stanford University School of Medicine, Azienda Toscana Centro, Northwestern University Feinberg School of Medicine, Columbia University Mailman School of Public Health, University of North Carolina, Chapel Hill, University of Mississippi Medical Center, Fred Hutchinson Cancer Research Center, Rutgers State University of New Jersey, and Wake Forrest School of Medicine

Quote: “Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging.”

#2: Nrf2 inhibits ferroptosis and protects against acute lung injury due to intestinal ischemia reperfusion via regulating SLC7A11 and HO-1

DOI: https://doi.org/10.18632/aging.103378

Authors: Hui Dong, Zhuanzhuan Qiang, Dongdong Chai, Jiali Peng, Yangyang Xia, Rong Hu, and Hong Jiang

Institution: Shanghai JiaoTong University School of Medicine 

Quote: “Acute lung injury (ALI) is a syndrome associated with a high mortality rate. Nrf2 is a key regulator of intracellular oxidation homeostasis that plays a pivotal role in controlling lipid peroxidation, which is closely related to the process of ferroptosis. However, the intrinsic effect of Nrf2 on ferroptosis remains to be investigated in ALI.”

#1: Optimizing future well-being with artificial intelligence: self-organizing maps (SOMs) for the identification of islands of emotional stability

DOI: https://doi.org/10.18632/aging.204061

Authors: Fedor Galkin, Kirill Kochetov, Michelle Keller, Alex Zhavoronkov, and Nancy Etcoff

Institutions: Deep Longevity Limited, Insilico Medicine, Buck Institute for Research on Aging, and Harvard Medical School

Quote: “In this article, we present a deep learning model of human psychology that can predict one’s current age and future well-being. We used the model to demonstrate that one’s baseline well-being is not the determining factor of future well-being, as posited by hedonic treadmill theory. Further, we have created a 2D map of human psychotypes and identified the regions that are most vulnerable to depression. This map may be used to provide personalized recommendations for maximizing one’s future well-being.”

Click here to read the latest papers published by Aging.

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Aging is an open-access, peer-reviewed journal that has published high-impact research papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

For media inquiries, please contact [email protected].

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BMI Correlates With Accelerated Epigenetic Aging in Young Adults

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In a recent study, researchers from the University of Alabama at Birmingham’s Department of Pediatrics examined the relationship between measures of obesity and DNA methylation in young adults.

BMI Correlates With Accelerated Epigenetic Aging in Young Adults

The Trending With Impact series highlights Aging publications (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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While the study of genetics focuses on heredity and alterations in the genetic code itself, epigenetics refers to the changes in gene expression that occur as a result of environmental or lifestyle factors. Advances in epigenetic research have allowed measures of DNA methylation (DNAm) (epigenetic clocks) to illustrate clear links between obesity, accelerated epigenetic aging and a variety of negative health outcomes in older adults. Despite these advances, there is a lack of research about these correlations and sex-based variations among young adults. The ability to detect accelerated epigenetic aging in young adulthood could potentially be used to prevent the onset of chronic diseases and improve health outcomes later in life.

“Moreover, few studies have included replication across measures of obesity and epigenetic aging to examine the robustness or specificity of these effects. Finally, little is known about sex differences in the links between obesity and epigenetic aging, despite evidence of substantial sex dimorphism in both physiological and epigenetic aging [20].”

In a recent study, researchers Christy Anne Foster, Malcolm Barker-Kamps, Marlon Goering, Amit Patki, Hemant K. Tiwari, and Sylvie Mrug from the University of Alabama at Birmingham’s Department of Pediatrics examined the relationship between obesity and measures of DNAm in young adults. They also investigated whether there is a sex-dependant correlation between obesity and DNAm in young adults. On January 18, 2023, their research paper was published in Aging’s Volume 15, Issue 2, and entitled, “Epigenetic age acceleration correlates with BMI in young adults.”

Research and Results

Here, the researchers explored the relationship between measures of obesity and epigenetic age acceleration in young adults. The team included a cross-sectional community sample of 290 healthy young adults—with 60% being female, 80% African American, 18% White, and a total mean age of 27 years old. The researchers measured participant BMI and waist circumference, and also calculated their epigenetic age acceleration using four epigenetic age estimators (derived from salivary DNA): Hannum DNAm, Horvath DNAm, Phenoage DNAm, and GrimAge DNAm. In addition, they collected data on covariates, including age, sex, race, parental education, and income-to-needs ratio.

After covariates were adjusted for, the researchers found that DNAm PhenoAge was higher in participants who had higher body mass index (BMI) and waist circumference in both sexes, with a stronger effect on BMI in males compared to females. Horvath DNA methylation age was associated with participants who had larger waist circumferences, but not BMI. Higher Hannum DNAm age was associated with both higher BMI and waist circumference in men, but not in women. In this study, GrimAge was not associated with either BMI or waist circumference. As a whole, none of the associations with the DNAm indicators varied by race. The researchers found that scoring higher on one or more of the four DNAm indicators was associated with an older chronological age, lower socioeconomic status, being female and White, as well as saliva cell composition. 

“Together, these results suggest that higher BMI and waist circumference are associated with higher epigenetic age in young adulthood. Because the analyses adjusted for chronological age, associations with higher epigenetic age indicate faster epigenetic aging [22]. Importantly, this study demonstrated associations between obesity and epigenetic aging using DNA from saliva, which involves a non-invasive sample collection compared to other tissues (e.g., blood) and thus can be more readily translated into clinical practice, highlighting the usefulness in young adults.”

Significance and Limitations

These findings are significant because they suggest that body weight plays a role in determining epigenetic age acceleration, which in turn can affect overall health and lifespan. Previous research has shown that epigenetic age acceleration is associated with increased risk for age-related diseases such as cardiovascular disease, type 2 diabetes and certain cancers. However, it is important to note that this study only shows a correlation between BMI and epigenetic age acceleration and does not provide evidence of causality. It is possible that other factors, such as diet, exercise and stress levels, could also contribute to the relationship between BMI and epigenetic age acceleration.

The authors were forthcoming about several study limitations in their research paper, including a relatively small sample size which limited statistical power and precluded rigorous analysis of individual CpG sites. The original sample was locally representative but experienced some differential attrition over time, which could limit generalizability to certain populations. Epigenetic clocks have been tested primarily in White populations and may be less relevant to African American individuals who comprised the majority of this sample. This study used salivary DNA, so replication using DNA extracted from other tissues will be important for future work. The cross-sectional design did not allow testing directional effects between BMI and epigenetic aging over time. None of the CpGs used in calculating methylation age were part of known causal effect on BMI as per Mendelian Randomization studies; further modeling with outcomes from other tissues impacted by obesity may provide more insight into methylation aging process.

Conclusions

In conclusion, this study sheds light on the relationship between BMI and epigenetic age acceleration in young adults. The results suggest that young adults with higher BMIs may be aging faster and at a higher risk for age-related diseases. These findings highlight the importance of maintaining a healthy weight and lifestyle, not only for weight management but also for overall health and lifespan.

In the context of the growing obesity epidemic and the increasing focus on personalized medicine and preventive health, this study provides valuable insights into the potential health impacts of body weight and the role of epigenetics in health and disease. Further research is needed to fully understand the mechanisms behind this relationship and to determine the best approaches for improving health and lifespan in young adults.

“In conclusion, this study extends prior research by demonstrating the association between obesity and salivary epigenetic aging in young adult males and females. These findings are of interest to those who are interested in epigenetic age acceleration as a potential biomarker. They also support future research examining obesity as a causal risk factor for epigenetic age acceleration. The findings underscore the importance of testing sex differences and including multiple epigenetic clocks in future research. Overall, the present results add to mounting evidence that obesity affects cellular aging across multiple tissues early in the lifespan.”

Click here to read the full research paper published by Aging.

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Aging is an open-access, peer-reviewed journal that has published high-impact research papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

For media inquiries, please contact [email protected].

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Gene Linked to Osteoporosis Risk in Postmenopausal Asian Women

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In this recent study, researchers compared three IGF-1 polymorphisms in postmenopausal Asian women and investigated their potential link to osteoporosis.

Gene Linked to Osteoporosis Risk in Postmenopausal Asian Women

The Trending With Impact series highlights Aging publications (listed as “Aging (Albany NY)” by Medline/PubMed and “Aging-US” by Web of Science) that attract higher visibility among readers around the world online, in the news, and on social media—beyond normal readership levels. Look for future science news about the latest trending publications here, and at Aging-US.com.

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Osteoporosis is characterized by the loss of bone density and an increased risk of fractures. This serious health condition is a major public health concern, particularly among older women. According to the National Osteoporosis Foundation, approximately 80% of the estimated 10 million Americans with osteoporosis are women. Additionally, roughly one in two women over the age of 50 will break a bone due to osteoporosis. 

“Osteoporosis (OP) is prevalent in postmenopausal women. Several studies investigated the association between IGF-1 polymorphisms and OP among postmenopausal females with conflicting outcomes.”

While the main risk factor for osteoporosis is undeniably aging, the causes of osteoporosis are more complex—involving a combination of genetic and environmental factors. The insulin-like growth factor 1 (IGF-1) gene plays a critical role in bone growth and development, and previous studies have suggested that variations in this gene may be associated with osteoporosis. Some genetic variants have been found to be associated with decreased IGF-1 levels, which may contribute to the development of osteoporosis.

In a recent study, researchers Sui-Lung Su, Yung-Hsun Huang, Yu-Hsuan Chen, Pi-Shao Ko, Wen Su, Chih-Chien Wang, and Meng-Chang Lee from the Tri-Service General Hospital and National Defense Medical Center in Taipei, Taiwan, explored the relationship between IGF-1 polymorphisms rs35767, rs2288377 and rs5742612 and the development of osteoporosis in postmenopausal Asian women. Their new research paper was published in Aging’s Volume 15, Issue 1, entitled, “A case-control study coupling with meta-analysis elaborates decisive association between IGF-1 rs35767 and osteoporosis in Asian postmenopausal females.”

“Although two meta-analyses have been published, conclusion of the association between IGF-1 and OP is pending, probably due to limited studies on postmenopausal women [21, 22].”

The Study

To further investigate the association between IGF-1 variants, osteoporosis and postmenopausal women, the researchers conducted a case-control study involving a cohort of postmenopausal women in Taiwan. The study included a total of 95 women with osteoporosis and 222 age-matched controls without this condition. The researchers genotyped the participants for the three IGF-1 variants and analyzed the data to determine the association between these variants and osteoporosis.

The results of the study revealed an association between the rs35767 variant and osteoporosis in these postmenopausal Asian women. Women with the variant had an increased risk of osteoporosis compared to those without the variant. In addition to the case-control study, the researchers also conducted a meta-analysis to combine the results of previous studies on the topic. This meta-analysis included their current findings and three other studies (published in English), totaling 2,267 individuals. The meta-analysis confirmed the results of their case-control study and found a significant association between the rs35767 variant and risk of osteoporosis in postmenopausal Asian women. 

“We reveal a conclusive risk association in rs35767 with OP in postmenopausal females judged by TSA with 2,267 Asians in a combination of 3 published studies and our case-control study. However, rs2288377 and rs5742612 show no association with OP but it needs more sample sizes to evaluate the relationship.”

Conclusion

In conclusion, this research paper provides strong evidence for a decisive association between the rs35767 variant in the IGF-1 gene and the development of osteoporosis in postmenopausal Asian women. The study suggests that this variant may be a significant genetic risk factor for osteoporosis in this population. Their research could help in understanding the genetic basis of osteoporosis and also pave the way for personalized medicine in the management of this condition in the future. Identifying individuals at high risk for osteoporosis based on their genetic profile could allow for early detection and interventions to prevent or delay the onset of this disease. However, more research is needed to confirm these findings in other populations and to compare this study with other studies that have not been documented in the English language.

“To conclude, our case-control study is a crucial sample in meta-analysis to reach [the] conclusion of the association between IGF-1 rs35767 and OP in postmenopausal women.”

Click here to read the full research paper published by Aging.

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Aging is an open-access, peer-reviewed journal that has published high-impact research papers in all fields of aging research since 2009. These papers are available to readers (at no cost and free of subscription barriers) in bi-monthly issues at Aging-US.com.

For media inquiries, please contact [email protected].

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How Hidden Markov Models Could Elucidate Multimorbidity in Aging

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In a new study, researchers investigated longitudinal multimorbidity patterns among older adults from a Swedish urban population.

Figure 1. Evolution and transitions of multimorbidity patterns over time by age group (N=3,363).
Figure 1. Evolution and transitions of multimorbidity patterns over time by age group (N=3,363).
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Multimorbidity is a term that refers to living with two or more chronic diseases at the same time, and the prevalence of this phenomenon increases with age. In addition, humans tend to evolve and transition into distinct patterns of multimorbidity. These still ill-defined patterns of multimorbidity may offer a window of opportunity for researchers. Since the aging population continues to grow in many parts of the world, researchers are motivated to better understand these patterns and how they evolve and transition over time in order to develop interventions and therapeutics for healthier aging. However, this is a challenging task for several reasons.

“Multimorbidity is associated with a higher risk of polypharmacy and decreased quality of life, and challenges the decision-making of clinicians that lack effective guidelines for the management and treatment of patients with cohexisting complex diseases [4].”

Multimorbidity Patterns

While researchers have investigated multimorbidity, not all studies are created equal—rendering meta-analyses largely incongruent (thus far). One reason the evolution of multimorbidity patterns is so challenging to study is because most study designs are not powered to account for the dynamic nature of multimorbidity in old age. Another reason is that various studies use different lists of diseases. (Some studies include ten conditions or less and others include 200+ conditions.) Finally, most statistical methods used to organize data are not able to properly handle the complexity of multimorbidity.

“Exploring how multimorbidity patterns evolve throughout people’s lives and the time subjects remain within specific patterns is still an under-researched area [7, 8]. The understanding of how diseases cluster longitudinally in specific age groups would pave the way to the design of new prognostic tools, as well as new preventive and, eventually, therapeutic approaches.”

In a new study, researchers Albert Roso-Llorach, Davide L. Vetrano, Caterina Trevisan, Sergio Fernández, Marina Guisado-Clavero, Lucía A. Carrasco-Ribelles, Laura Fratiglioni, Concepción Violán, and Amaia Calderón-Larrañaga from the Jordi Gol i Gurina University Institute Foundation for Research in Primary Health Care (IDIAPJGol), Universitat Autònoma de Barcelona, Karolinska Institutet, Stockholm University, Stockholm Gerontology Research Center, University of Ferrara, Madrid Health Service, and Universitat Politecnica de Catalunya investigated the evolution of multimorbidity patterns in a longitudinal study using complex statistical models. The team published their research paper in Aging’s Volume 14, Issue 24, entitled, “12-year evolution of multimorbidity patterns among older adults based on Hidden Markov Models.”

Hidden Markov Models 

“Recently, several advanced machine-learning techniques such as non-hierarchical and hierarchical clustering techniques have been used to explore multimorbidity patterns.”

Hidden Markov Models (HMM) were developed based on the Bayesian Information Criterion. The Bayesian Information Criterion is an algorithm of inference that is used to select the best model from a set of possible models. It is a powerful technique for analyzing temporal data that can capture dynamic changes in longitudinal patterns over time. Since HMMs can account for complex longitudinal data, they are well-suited to investigate the dynamics of multimorbidity over time.

The Study

In this study, HMMs were used to investigate 3,363 older adults from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) and the evolution of their multimorbidity patterns over the course of 12 years. The aim of this research was to explore the evolution of these patterns across decades of life in older adults and to examine how they transition across different chronic diseases when further chronic diseases arise. In this cohort of study participants, the average age was 76.1 years old, 66.6% were female and 87.2% had multimorbidity at baseline.

The researchers divided the participants into three groups based on age: sexagenarians (between 60 and 66 years), septuagenarians (between 72 and 78 years) and octogenarians (81 years and over). Data used in the HMMs included age, gender, education level, self-reported chronic diseases and medications, results from a Mini Mental State Examination (MMSE), and walking speed. Data were collected from participants at baseline and at six and 12 years (three separate time points).

“At each follow-up wave, SNAC-K participants undergo an approximately five-hour-long comprehensive clinical and functional assessment carried out by trained physicians, nurses, and neuropsychologists.”

Results

The team identified four longitudinal multimorbidity patterns in each decade. The Unspecific pattern consists of participants with no specific pattern of multimorbidity. In all decades, participants showed the shortest permanence time in the Unspecific pattern. The researchers also included categories for participants who dropped out of the study or passed away.

Next, the top 10 diseases were selected out of each age group at each follow-up wave to identify the most common multimorbidity patterns. Among the sexagenarians, the multimorbidity patterns were clustered into cardiovascular and anemia, cardio-metabolic, and psychiatric-endocrine and sensorial. Among the septuagenarians, the multimorbidity patterns were clustered into cardiovascular and diabetes, neuro-vascular and skin-sensorial, and neuro-psychiatric and sensorial. Among the octogenarians, the multimorbidity patterns were clustered into respiratory-circulatory and skin, cardio-respiratory and neurological, and neuro-sensorial. The data showed that participants commonly shifted from one pattern to another. (See Figure 1.)

“In this study we identified and characterized longitudinal multimorbidity patterns among older adults from a Swedish urban population, and estimated the time they spent in each pattern as well as the probability of transitioning across different patterns throughout a 12-year follow-up period.”

Conclusions

“Our statistical approach enabled us to model the evolution and transitions of multimorbidity over time, and the results of this could be applied in the interests of healthier aging. Moreover, the age-stratified analyses allowed us to identify which disease combinations and transitions were more prevalent in each decade.”

The findings of this study suggest that multimorbidity patterns change with age and highlight the importance of understanding the dynamic nature of multimorbidity over time. Through the use of HMMs, this research was able to detect changes in the prevalence and transition of multimorbidity patterns across different decades of life. These findings can help healthcare providers and researchers better understand the complex nature of multimorbidity and develop more effective interventions for older adults. Furthermore, this research provides evidence that the use of HMMs to study longitudinal data is a useful tool for further research into multimorbidity. Additional studies with more data is needed to gain a better understanding of the interplay between multimorbidity and aging.

“Our study provides evidence that multimorbidity is dynamic and heterogeneous in old age. With increasing age, older adults experience decreasing clinical stability and progressively shorter permanence time within one same multimorbidity pattern. Moreover, a significant proportion ranging between 5.9%-22.6% belongs to an Unspecific pattern with a low burden of diseases and a promising preventive potential. Adding new variables related to drug use, environmental and genetic factors, and/or frailty to the longitudinal analysis of multimorbidity patterns may allow optimizing the epidemiological understanding and applicability of these models for patient-tailored prevention and management strategies.”

Click here to read the full research paper published by Aging.

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Aging is an open-access journal that publishes research papers bi-monthly in all fields of aging research. These papers are available at no cost to readers on Aging-us.com. Open-access journals have the power to benefit humanity from the inside out by rapidly disseminating information that may be freely shared with researchers, colleagues, family, and friends around the world.

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