Aging-US

Blog summary of "Epigenetic age acceleration correlates with BMI in young adults" published in Volume 15, Issue 2 of Aging (Aging-US). ___________________________________________ 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.” Full blog - https://aging-us.org/2023/02/bmi-correlates-with-accelerated-epigenetic-aging-in-young-adults/ DOI - https://doi.org/10.18632/aging.204492 Corresponding author - Christy Anne Foster - cafoster@uabmc.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204492 Keywords - obesity, epigenetic aging, young adult, DNA methylation, epigenetic acceleration About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 2, entitled, “Body weight influences musculoskeletal adaptation to long-term voluntary wheel running during aging in female mice.” Aging increases the prevalence of sarcopenia and osteoporosis that are often both components of a musculoskeletal syndrome, osteosarcopenia. Osteosarcopenia is highly associated with frailty, falls, fractures, and disability, leading to decreased quality of life and increased morbidity and mortality. Frailty is the hallmark of aging that can be delayed with exercise. In this new research paper, researchers Yukiko Kitase, Julian A. Vallejo, Sarah L. Dallas, Yixia Xie, Mark Dallas, LeAnn Tiede-Lewis, David Moore, Anthony Meljanac, Corrine Kumar, Carrie Zhao, Jennifer Rosser, Marco Brotto, Mark L. Johnson, Ziyue Liu, Michael J. Wacker, and Lynda Bonewald from Indiana University, University of Missouri and University of Texas wrote that the present studies were initiated based on the hypothesis that long-term voluntary wheel running (VWR) in female mice from 12 to 18 or 22 months of age would have beneficial effects on the musculoskeletal system. “Frequently osteoporosis and sarcopenia occur concurrently. It is not known if one precedes the other or if one condition influences disease progression of the other condition [26, 27]. We hypothesized that long-term voluntary exercise started later in life (12 months of age) would improve both skeletal muscle and bone parameters in aging female mice up to 22 months.” Mice were separated into high (HBW) and low (LBW) body weight based on final body weights upon termination of experiments. Bone marrow fat was significantly higher in HBW than LBW under sedentary conditions, but not with VWR. HBW was more protective for soleus size and function than LBW under sedentary conditions, however VWR increased soleus size and function regardless of body weight. VWR plus HBW was more protective against muscle loss with aging. Similar effects of VWR plus HBW were observed with the extensor digitorum longus, EDL, however, LBW with VWR was beneficial in improving EDL fatigue resistance in 18 mo mice and was more beneficial with regards to muscle production of bone protective factors. VWR plus HBW maintained bone in aged animals. In summary, HBW had a more beneficial effect on muscle and bone with aging especially in combination with exercise. These effects were independent of bone marrow fat, suggesting that intrinsic musculoskeletal adaptions were responsible for these beneficial effects.” “Collectively, VWR has beneficial effects on bone health during advanced aging regardless of body weight, but VWR differentially alters bone parameters depending on body weight, with modifications in mechanical properties in LBW but structural modifications in HBW contributing to the prevention of osteopenia.” Full Paper: DOI: https://doi.org/10.18632/aging.204390 Corresponding Authors: Lynda Bonewald -bonewal@iu.edu, Michael J. Wacker - wackerm@umkc.edu About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Website - https://www.Aging-US.com SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/

A new research perspective was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 2, entitled, “Are menopause, aging and prostate cancer diseases?” In this new research perspective, researcher Mikhail (Misha) Blagosklonny M.D., Ph.D., from Roswell Park Comprehensive Cancer Center wrote in the abstract: “There is no doubt that prostate cancer is a disease. Then, according to hyperfunction theory, menopause is also a disease. Like all age-related diseases, it is a natural process, but is also purely harmful, aimless and unintended by nature. But exactly because these diseases (menopause, prostate enlargement, obesity, atherosclerosis, hypertension, diabetes, presbyopia and thousands of others) are partially quasi-programmed, they can be delayed by slowing aging. Is aging a disease? Aging is a quasi-programmed disease that is partially treatable by rapamycin. On the other hand, aging is an abstraction, a sum of all quasi-programmed diseases and processes. In analogy, the zoo consists of animals and does not exist without animals, but the zoo is not an animal.” Read the Full Paper: DOI: https://doi.org/10.18632/aging.204499 Corresponding Author: Mikhail V. Blagosklonny Corresponding Emails: Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com Keywords: geroscience, mTOR, hyperfunction theory of aging, lifespan, healthspan Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204499 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published on the cover of Aging (Aging-US)) Volume 15, Issue 2, entitled, “Clearance of p16Ink4a-positive cells in a mouse transgenic model does not change β-cell mass and has limited effects on their proliferative capacity.” Type 2 diabetes is partly characterized by decreased β-cell mass and function which have been linked to cellular senescence. Despite a low basal proliferative rate of adult β-cells, they can respond to growth stimuli, but this proliferative capacity decreases with age and correlates with increased expression of senescence effector, p16Ink4a. In a new study, researchers Nadine Bahour, Lucia Bleichmar, Cristian Abarca, Emeline Wilmann, Stephanie Sanjines, and Cristina Aguayo-Mazzucato from the Joslin Diabetes Center at Harvard Medical School hypothesized that selective deletion of p16Ink4a-positive cells would enhance the proliferative capacity of the remaining β-cells due to the elimination of the local senescence-associated secretory phenotype (SASP). “We aimed to investigate the effects of p16Ink4a-positive cell removal on the mass and proliferative capacity of remaining β-cells using INK-ATTAC mice as a transgenic model of senolysis.” Clearance of p16Ink4a-positive subpopulation was tested in mice of different ages, males and females, and with two different insulin resistance models: high-fat diet (HFD) and insulin receptor antagonist (S961). Clearance of p16Ink4a-positive cells did not affect the overall β-cell mass. β-cell proliferative capacity negatively correlated with cellular senescence load and clearance of p16Ink4a positive cells in 1-year-old HFD mice improved β-cell function and increased proliferative capacity in a subset of animals. Single-cell sequencing revealed that the targeted p16Ink4a subpopulation of β-cells is non-proliferative and non-SASP producing whereas additional senescent subpopulations remained contributing to continued local SASP secretion. “In conclusion, deletion of p16Ink4a cells did not negatively impact beta-cell mass and blood glucose under basal and HFD conditions and proliferation was restored in a subset of HFD mice opening further therapeutic targets in the treatment of diabetes.” DOI: https://doi.org/10.18632/aging.204483 Corresponding Author: Cristina Aguayo-Mazzucato - cristina.aguayo-mazzucato@joslin.harvard.edu Keywords: beta cells, mass, proliferation, senolysis, senescence Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204483 About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Blog summary of a recent research paper published by Aging: "A case-control study coupling with meta-analysis elaborates decisive association between IGF-1 rs35767 and osteoporosis in Asian postmenopausal females." ____________________________________________________ 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.” Full blog - https://aging-us.org/2023/01/gene-linked-to-osteoporosis-risk-in-postmenopausal-asian-women/ DOI - https://doi.org/10.18632/aging.204464 Corresponding author - Meng-Chang Lee - apply0710@yahoo.com.tw Keywords - osteoporosis, postmenopausal, insulin-like growth factor-1, single nucleotide polymorphism, meta-analysis About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ For media inquiries, please contact: media@impactjournals.com.

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 1, entitled, “The innate immune signaling component FBXC-58 mediates dietary restriction effects on healthy aging in Caenorhabditis elegans.” Dietary restriction (DR) is a highly effective and reproducible intervention that prolongs longevity in many organisms. The molecular mechanism of action of DR is tightly connected with the immune system; however, the detailed mechanisms and effective downstream factors of immunity that mediate the beneficial effects of DR on aging remain unknown. In this new study, researchers Jeong-Hoon Hahm, Farida S. Nirmala, Pyeong Geun Choi, Hyo-Deok Seo, Tae Youl Ha, Chang Hwa Jung, and Jiyun Ahn from the Korea Food Research Institute and the University of Science and Technology (in Daejeon, South Korea) investigated the immune signaling that mediates DR effects. The team used Caenorhabditis elegans (C. elegans) to understand the underlying molecular mechanisms of aging and immunity. “We found that the F-box gene, fbxc-58, a regulator of the innate immune response, is a novel mediator of DR effects on extending the health span of C. elegans.” Fbxc-58 is upregulated by DR and is necessary for DR-induced lifespan extension and physical health improvement in C. elegans. Furthermore, through DR, fbxc-58 prevents disintegration of the mitochondrial network in body wall muscle during aging. The researchers found that fbxc-58 is a downstream target of the ZIP-2 and PHA-4 transcription factors, the well-known DR mediator, and fbxc-58 extends longevity in DR through an S6 kinase-dependent pathway. Thus, the team proposed that fbxc-58 may provide a new mechanistic understanding of the effects of DR on healthy aging and elucidate the signaling mechanisms that link immunity and DR effects with aging. “Thus, we propose that investigating the molecular mechanism of action of F-box proteins, including fbxc-58, in DR will shed light on means to prevent sarcopenia and offer a potentially practical means of encouraging healthy aging via DR.” DOI: https://doi.org/10.18632/aging.204477 Corresponding Authors: Jeong-Hoon Hahm - hahmjh@kfri.re.kr, Jiyun Ahn - jyan@kfri.re.kr Keywords: dietary restriction, aging, innate immunity, F-box protein, Caenorhabditis elegans Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204477 About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://youtube.com/Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ For media inquiries, please contact: media@impactjournals.com

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 1, entitled, “Genetic deficiency and pharmacological modulation of RORα regulate laser-induced choroidal neovascularization.” Choroidal neovascularization (CNV) causes acute vision loss in neovascular age-related macular degeneration (AMD). Genetic variations of the nuclear receptor RAR-related orphan receptor alpha (RORα) have been linked with neovascular AMD, yet its specific role in pathological CNV development is not entirely clear. In this new study, researchers Chi-Hsiu Liu, Felix Yemanyi, Kiran Bora, Neetu Kushwah, Alexandra K. Blomfield, Theodore M. Kamenecka, John Paul SanGiovanni, Ye Sun, Laura A. Solt, and Jing Chen from Harvard Medical School, UF Scripps Biomedical Research and University of Arizona showed that Rora was highly expressed in the mouse choroid compared with the retina, and genetic loss of RORα in Staggerer mice (Rorasg/sg) led to increased expression levels of Vegfr2 and Tnfa in the choroid and retinal pigment epithelium (RPE) complex. “Here, we investigated whether RORα regulates CNV using a mouse model of laser-induced CNV, mimicking the neovascular features of wet AMD. We found that expression of RORα was enriched in the mouse choroid/RPE complex and upregulated in laser-induced CNV.” In a mouse model of laser-induced CNV, RORα expression was highly increased in the choroidal/RPE complex post-laser, and loss of RORα in Rorasg/sg eyes significantly worsened CNV with increased lesion size and vascular leakage, associated with increased levels of VEGFR2 and TNFα proteins. Pharmacological inhibition of RORα also worsened CNV. In addition, both genetic deficiency and inhibition of RORα substantially increased vascular growth in isolated mouse choroidal explants ex vivo. RORα inhibition also promoted angiogenic function of human choroidal endothelial cell culture. “Together, our results suggest that RORα negatively regulates pathological CNV development in part by modulating angiogenic response of the choroidal endothelium and inflammatory environment in the choroid/RPE complex.” DOI: https://doi.org/10.18632/aging.204480 Corresponding Author: Jing Chen - jing.chen@childrens.harvard.edu Keywords: age-related macular degeneration, angiogenesis, choroidal neovascularization, inflammation, nuclear receptors, RORα, VEGFR2, TNFα Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204480 About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.

A new research paper was published on the cover of Aging (listed as "Aging (Albany NY)" by Medline/PubMed and "Aging-US" by Web of Science) Volume 15, Issue 1, entitled, “Single-cell transcriptomics of peripheral blood in the aging mouse.” Compositional and transcriptional changes in the hematopoietic system have been used as biomarkers of immunosenescence and aging. In this new study, researchers Yee Voan Teo, Samuel J. Hinthorn, Ashley E. Webb, and Nicola Neretti from Brown University used single-cell RNA-sequencing to study the aging peripheral blood in mice and characterize the changes in cell-type composition and transcriptional profiles associated with age. “Here, we applied scRNA-seq on young and old mice to dissect the transcriptional and cell composition changes of all cell types in the peripheral blood with age.” The team identified 17 clusters from a total of 14,588 single cells. They detected a general upregulation of antigen processing and presentation and chemokine signaling pathways and a downregulation of genes involved in ribosome pathways with age. In old peripheral blood, the researchers also observed an increased percentage of cells expressing senescence markers (Cdkn1a, and Cdkn2a). In addition, a cluster of activated T cells exclusively found in old blood was detected, with lower expression of Cd28 and higher expression of Bcl2 and Cdkn2a, suggesting that the cells are senescent and resistant to apoptosis. “Finally, targeting senescent cells using genetic approaches has been shown to ameliorate the aging phenotype [34, 35]. More recently, senolytics drugs are being identified or developed to target apoptotic pathways because senescent cells are known to be apoptosis-resistant [34]. Therefore, the Bcl2+ old T cells that we identified in old mice can potentially be targeted pharmacologically to ameliorate the phenotypes associated with the aging of the immune system.” DOI: https://doi.org/10.18632/aging.204471 Corresponding Author: Nicola Neretti - nicola_neretti@brown.edu Keywords: aging, single-cell transcriptomics, senescence, peripheral blood Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204471 About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.

A new research paper was published in Aging (Aging-US) Volume 14, Issue 24, entitled, “Transcriptomic analysis of human ALS skeletal muscle reveals a disease-specific pattern of dysregulated circRNAs.” Circular RNAs are abundant, covalently closed transcripts that arise in cells through back-splicing and display distinct expression patterns across cells and developmental stages. While their functions are largely unknown, their intrinsic stability has made them valuable biomarkers in many diseases. In this new study, researchers Dimitrios Tsitsipatis, Krystyna Mazan-Mamczarz, Ying Si, Allison B. Herman, Jen-Hao Yang, Abhishek Guha, Yulan Piao, Jinshui Fan, Jennifer L. Martindale, Rachel Munk, Xiaoling Yang, Supriyo De, Brijesh K. Singh, Ritchie Ho, Myriam Gorospez, and Peter H. King from the National Institutes of Health’s National Institute on Aging, The University of Alabama at Birmingham, Birmingham Veterans Affairs Medical Center, and Cedars-Sinai Medical Center set out to examine circRNA patterns in amyotrophic lateral sclerosis (ALS). By RNA-sequencing analysis, the researchers first identified circRNAs and linear RNAs that were differentially abundant in skeletal muscle biopsies from ALS compared to normal individuals. “By RT-qPCR analysis, we confirmed that 8 circRNAs were significantly elevated and 10 were significantly reduced in ALS, while the linear mRNA counterparts, arising from shared precursor RNAs, generally did not change.” Several of these circRNAs were also differentially abundant in motor neurons derived from human induced pluripotent stem cells (iPSCs) bearing ALS mutations, and across different disease stages in skeletal muscle from a mouse model of ALS (SOD1G93A). Interestingly, a subset of the circRNAs significantly elevated in ALS muscle biopsies were significantly reduced in the spinal cord samples from ALS patients and ALS (SOD1G93A) mice. In sum, the researchers identified differentially abundant circRNAs in ALS-relevant tissues (muscle and spinal cord) that could inform about neuromuscular molecular programs in ALS and guide the development of therapies. “As our studies advance, we will investigate the function of the most promising and abundant circRNAs, among the 18 circRNAs reported here. We are especially interested in those that appeared to be specific for ALS (Figure 2), as they may help to characterize disease-associated molecular pathways that could be targeted therapeutically.” DOI: https://doi.org/10.18632/aging.204450 Corresponding Authors: Myriam Gorospe - GorospeM@grc.nia.nih.gov, Dimitrios Tsitsipatis - dimitrios.tsitsipatis@nih.gov, Peter H. King - phking@uabmc.edu Keywords: amyotrophic lateral sclerosis, circular RNAs, neurodegenerative disease, human skeletal muscle, human spinal cord tissue About Aging-US: Launched in 2009, Aging (Aging-US) publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at www.Aging-US.com​​ and connect with us: SoundCloud – https://soundcloud.com/Aging-Us Facebook – https://www.facebook.com/AgingUS/ Twitter – https://twitter.com/AgingJrnl Instagram – https://www.instagram.com/agingjrnl/ YouTube – https://www.youtube.com/agingus​ LinkedIn – https://www.linkedin.com/company/aging/ Reddit – https://www.reddit.com/user/AgingUS Pinterest – https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.

Listen to a blog summary of a research paper published by Aging in Volume 14, Issue 24, entitled, "12-year evolution of multimorbidity patterns among older adults based on Hidden Markov Models." _______________________________________ 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].” 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.” Full blog - https://aging-us.org/2023/01/how-hidden-markov-models-can-help-elucidate-multimorbidity-in-aging/ DOI - https://doi.org/10.18632/aging.204395 Corresponding authors - Albert Roso-Llorach - aroso@idiapjgol.org, Amaia Calderón-Larrañaga - amaia.calderon.larranaga@ki.se Keywords - multimorbidity, older adults, longitudinal population-based study, aging, Hidden Markov Models About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ For media inquiries, please contact media@impactjournals.com.