Aging-US

A new research paper was published in Aging (Aging-US) Volume 14, Issue 24, entitled, “Epigenetic aging is associated with aberrant neural oscillatory dynamics serving visuospatial processing in people with HIV.” Despite effective antiretroviral therapy, cognitive impairment and other aging-related comorbidities are more prevalent in people with HIV (PWH) than in the general population. Previous research examining DNA methylation has shown PWH exhibit accelerated biological aging. However, it is unclear how accelerated biological aging may affect neural oscillatory activity in virally suppressed PWH, and more broadly how such aberrant neural activity may impact neuropsychological performance. Participants (n = 134) between the ages of 23 – 72 years underwent a neuropsychological assessment, a blood draw to determine biological age via DNA methylation, and a visuospatial processing task during magnetoencephalography (MEG). Researchers Mikki Schantell, Brittany K. Taylor, Rachel K. Spooner, Pamela E. May, Jennifer O’Neill, Brenda M. Morsey, Tina Wang, Trey Ideker, Sara H. Bares, Howard S. Fox, and Tony W. Wilson from the Boys Town National Research Hospital, University of Nebraska Medical Center, Creighton University, Heinrich-Heine University, and the University of California San Diego focused their analyses on the relationship between biological age and oscillatory theta (4-8 Hz) and alpha (10 - 16 Hz) activity among PWH (n=65) and seronegative controls (n = 69). “To our knowledge, no study to date has directly linked accelerated biological aging in PWH to the neuro-functional changes that occur in cognitively impaired PWH, which include deficits in visuospatial processing, attention, working memory, and motor function networks.” PWH had significantly elevated biological age when controlling for chronological age relative to controls. Biological age was differentially associated with theta oscillations in the left posterior cingulate cortex (PCC) and with alpha oscillations in the right medial prefrontal cortex (mPFC) among PWH and seronegative controls. Stronger alpha oscillations in the mPFC were associated with lower CD4 nadir and lower current CD4 counts, suggesting such responses were compensatory. Participants who were on combination antiretroviral therapy for longer had weaker theta oscillations in the PCC. Full press release - https://www.aging-us.com/news_room/Aging-Epigenetic-aging-associated-with-aberrant-neural-oscillatory-dynamics-serving-visuospatial-processing-in-people-with-HIV DOI: https://doi.org/10.18632/aging.204437 Corresponding Author: Tony W. Wilson - tony.wilson@boystown.org Keywords: HIV, epigenetics, biological age, visuospatial discrimination, oscillations 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. 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/ For media inquiries, 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 14, Issue 24, entitled, “Associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer’s disease biomarkers.” Capturing the genetic architecture of Alzheimer’s disease (AD) is challenging because of the complex interplay of genetic and non-genetic factors in its etiology. It has been suggested that AD biomarkers may improve the characterization of AD pathology and its genetic architecture. Most studies have focused on connections of individual genetic variants with AD biomarkers, whereas the role of combinations of genetic variants is substantially underexplored. In this new study for the Alzheimer’s Disease Neuroimaging Initiative, researchers, from Alexander M. Kulminski, Ethan Jain-Washburn, Elena Loiko, Yury Loika, Fan Feng, and Irina Culminskaya from Duke University and University of California examined the associations of the APOE ε2 and ε4 alleles and polygenic profiles comprising the ε4-encoding rs429358, TOMM40 rs2075650, and APOC1 rs12721046 polymorphisms with cerebrospinal fluid (CSF) and plasma amyloid β (Aβ40 and Aβ42) and tau biomarkers. “Here, we examine the associations of the APOE ε2 and ε4 alleles and the AD-risk-differentiating compound genotypes comprising rs429358, rs2075650, and rs12721046 SNPs with Aβ40, Aβ42, and tau AD biomarkers measured in CSF and plasma using data from three studies: the AD Neuroimaging Initiative (ADNI), the Atherosclerosis Risk in Communities (ARIC) study, and the Framingham Heart Study (FHS).” Findings from this study support associations of the ε4 alleles with both plasma and CSF Aβ42 and CSF tau, and the ε2 alleles with baseline, but not longitudinal, CSF Aβ42 measurements. The researchers found that the ε4-bearing polygenic profiles conferring higher and lower AD risks are differentially associated with tau but not Aβ42. Modulation of the effect of the ε4 alleles by TOMM40 and APOC1 variants indicates the potential genetic mechanism of differential roles of Aβ and tau in AD pathogenesis. “Our primary finding is that the ε4-bearing polygenic profiles conferring higher and lower AD risks are differently associated with tau but not Aβ42. The other main results of our work are characterizations of the associations of the APOE ε2 and ε4 alleles with Aβ40, Aβ42, and tau biomarkers in ADNI-1, ADNI-2/GO, ARIC, and three FHS cohorts.” DOI: https://doi.org/10.18632/aging.204384 Corresponding Author: Alexander M. Kulminski - kulminsk@duke.edu Keywords: aging, apolipoprotein E polymorphism, Alzheimer’s disease, haplotypes, Alzheimer’s disease biomarkers Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204384 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/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new research paper was published in Aging (Aging-US) Volume 14, Issue 23, entitled, “DNA methylation-based measures of biological aging and cognitive decline over 16-years: preliminary longitudinal findings in midlife.” DNA methylation-based (DNAm) measures of biological aging associate with increased risk of morbidity and mortality, but their links with cognitive decline are less established. In this new study, researchers Rebecca G. Reed, Judith E. Carroll, Anna L. Marsland, and Stephen B. Manuck from University of Pittsburgh and University of California examined changes over a 16-year interval in epigenetic clocks (the traditional and principal components [PC]-based Horvath, Hannum, PhenoAge, GrimAge) and pace of aging measures (Dunedin PoAm, Dunedin PACE) in 48 midlife adults enrolled in the longitudinal arm of the Adult Health and Behavior project (56% Female, baseline AgeM = 44.7 years), selected for discrepant cognitive trajectories. “We hypothesized that overall, cognitive Decliners would be biologically older compared to cognitive Maintainers.” Cognitive Decliners (N = 24) were selected based on declines in a composite score derived from neuropsychological tests and matched with participants who did not show any decline, Maintainers (N = 24). Multilevel models with repeated DNAm measures within person tested the main effects of time, group, and group by time interactions. DNAm measures significantly increased over time generally consistent with elapsed time between study visits. There were also group differences: overall, Cognitive Decliners had an older PC-GrimAge and faster pace of aging (Dunedin PoAm, Dunedin PACE) than Cognitive Maintainers. There were no significant group by time interactions, suggesting accelerated epigenetic aging in Decliners remained constant over time. Older PC-GrimAge and faster pace of aging may be particularly sensitive to cognitive decline in midlife. “In conclusion, these preliminary results suggest PC-GrimAge and DNAm based pace of aging measures (Dunedin PoAm and PACE) associate with 16-year, neuropsychologically-validated cognitive decline in midlife. The results warrant a larger-scale study to better examine longitudinal associations between changes in DNAm measures and changes across multiple cognitive domains. Ultimately, establishing DNAm measures as biomarkers of cognitive function in midlife may offer pre-clinical markers of a molecular aging mechanism that can help identify individuals at increased risk for cognitive impairment and dementia in later life.” DOI: https://doi.org/10.18632/aging.204376 Corresponding Author: Rebecca G. Reed - rebecca.reed@pitt.edu Keywords: epigenetic age, aging biomarker, pace of aging, geroscience, cognitive aging Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204376 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 about a recent research perspective published in Volume 14, Issue 23, entitled, “Reduce, Reuse, Recycle, Run ! : 4 Rs to improve cardiac health in advanced age.” _____________________________________________ Cardiac dysfunction is a major public health concern. While it can occur for various reasons at any age, the prevalence of cardiac dysfunction dramatically increases with advancing age. Unfortunately, the underlying mechanisms of age-related cardiac decline are still largely unknown. Thus, it is essential for researchers to uncover novel strategies to improve cardiac health at advanced ages. AUTOPHAGIC FLUX An important physiological process involved in maintaining cardiovascular homeostasis is autophagic flux. Autophagic flux is the process by which cells break down and recycle their own cellular components after they have become damaged or unnecessary. This process is essential for maintaining healthy cardiac function, as it slows age-related oxidative damage, reduces the accumulation of toxic lipid and protein aggregates, and improves energy metabolism. However, the efficiency of autophagic flux decreases with age, resulting in declined cardiac function. Given its crucial role and fading functioning, the search for strategies to improve autophagic flux may be essential for improving cardiovascular health as humans age. Researchers Jae Min Cho, Rajeshwary Ghosh, Sohom Mookherjee, Sihem Boudina, and J. David Symons from the University of Utah authored a new research perspective about nutraceutical, lifestyle and pharmacological interventions that can reduce age-associated cardiac dysfunction. On December 1, 2022, their research perspective was published in Aging’s Volume 14, Issue 23, entitled, “Reduce, Reuse, Recycle, Run ! : 4 Rs to improve cardiac health in advanced age.” “In the following sections we review evidence that age-associated cardiac dysfunction can be Reduced by boosting cardiomyocyte autophagy (i.e., the ability to Reuse and Recycle damaged/dysfunctional proteins) via spermidine, rapamycin, and caloric-restriction. In addition, we highlight a new report indicating that a physiological intervention i.e., Running, rejuvenates cardiomyocyte autophagic flux to an extent that lessens age-associated cardiac dysfunction.” Full blog - https://aging-us.org/2022/12/late-in-life-interventions-to-improve-cardiac-health/ DOI - https://doi.org/10.18632/aging.204415 Corresponding authors - Sihem Boudina: sihem.boudina@u2m2.utah.edu, and J. David Symons: J.David.Symons@hsc.utah.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204415 Keywords - aging, authophagy, exercise training, heart, cardiac function 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

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 23, entitled, “White matter hyperintensity load is associated with premature brain aging.” Brain age is an MRI-derived estimate of brain tissue loss that has a similar pattern to aging-related atrophy. White matter hyperintensities (WMHs) are neuroimaging markers of small vessel disease and may represent subtle signs of brain compromise. In this new study, researchers Natalie Busby, Sarah Newman-Norlund, Sara Sayers, Roger Newman-Norlund, Sarah Wilson, Samaneh Nemati, Chris Rorden, Janina Wilmskoetter, Nicholas Riccardi, Rebecca Roth, Julius Fridriksson, and Leonardo Bonilha from University of South Carolina, Medical University of South Carolina and Emory University tested the hypothesis that WMHs are independently associated with premature brain age in an original aging cohort. “We hypothesized that a higher WMH load is linearly associated with premature brain aging controlling for chronological age.” Brain age was calculated using machine-learning on whole-brain tissue estimates from T1-weighted images using the BrainAgeR analysis pipeline in 166 healthy adult participants. WMHs were manually delineated on FLAIR images. WMH load was defined as the cumulative volume of WMHs. A positive difference between estimated brain age and chronological age (BrainGAP) was used as a measure of premature brain aging. Then, partial Pearson correlations between BrainGAP and volume of WMHs were calculated (accounting for chronological age). Brain and chronological age were strongly correlated (r(163)=0.932, p<0.001). There was significant negative correlation between BrainGAP scores and chronological age (r(163)=-0.244, p<0.001) indicating that younger participants had higher BrainGAP (premature brain aging). Chronological age also showed a positive correlation with WMH load (r(163)=0.506, p<0.001) indicating older participants had increased WMH load. Controlling for chronological age, there was a statistically significant relationship between premature brain aging and WMHs load (r(163)=0.216, p=0.003). Each additional year in brain age beyond chronological age corresponded to an additional 1.1mm3 in WMH load. “WMHs are an independent factor associated with premature brain aging. This finding underscores the impact of white matter disease on global brain integrity and progressive age-like brain atrophy.” DOI: https://doi.org/10.18632/aging.204397 Corresponding Author: Natalie Busby - hethern@mailbox.sc.edu Keywords: brain age, white matter hyperintensity, brain health, aging, health Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204397 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 (listed as “Aging (Albany NY)” by MEDLINE/PubMed and “Aging-US” by Web of Science) Volume 14, Issue 23, entitled, “DNA methylation GrimAge version 2.” Researchers Ake T. Lu, Alexandra M. Binder, Joshua Zhang, Qi Yan, Alex P. Reiner, Simon R. Cox, Janie Corley, Sarah E. Harris, Pei-Lun Kuo, Ann Z. Moore, Stefania Bandinelli, James D. Stewart, Cuicui Wang, Elissa J. Hamlat, Elissa S. Epel, Joel D. Schwartz, Eric A. Whitsel, Adolfo Correa, Luigi Ferrucci, Riccardo E. Marioni, and Steve Horvath from the University of California Los Angeles, Altos Labs, University of Hawaii at Manoa, Fred Hutchinson Cancer Research Center, University of Edinburgh, National Institute on Aging, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Harvard T.H. Chan School of Public Health, University of California – San Francisco, and the University of Mississippi Medical Center previously described a DNA methylation (DNAm) based biomarker of human mortality risk DNAm GrimAge. In their current study, the researchers describe version 2 of GrimAge (trained on individuals aged between 40 and 92) which leverages two new DNAm based estimators of (log transformed) plasma proteins: high sensitivity C-reactive protein (logCRP) and hemoglobin A1C (logA1C). “To arrive at version 2 of GrimAge, we developed two additional DNAm based surrogates for plasma proteins that are widely used in the clinic (DNAm logCRP and DNAm logA1C).” The team evaluated GrimAge2 in 13,399 blood samples across nine study cohorts. After adjustment for age and sex, GrimAge2 outperforms GrimAge in predicting mortality across multiple racial/ethnic groups (meta P=3.6×10-167 versus P=2.6×10-144) and in terms of associations with age related conditions such as coronary heart disease, lung function measurement FEV1 (correlation= -0.31, P=1.1×10-136), computed tomography based measurements of fatty liver disease. The researchers presented evidence that GrimAge version 2 also applies to younger individuals and to saliva samples where it tracks markers of metabolic syndrome. DNAm logCRP is positively correlated with morbidity count (P=1.3×10-54). DNAm logA1C is highly associated with type 2 diabetes (P=5.8×10-155). DNAm PAI-1 outperforms the other age-adjusted DNAm biomarkers including GrimAge2 in correlating with triglyceride (cor=0.34, P=9.6×10-267) and visceral fat (cor=0.41, P=4.7×10-41). Overall, the team demonstrated that GrimAge version 2 is an attractive epigenetic biomarker of human mortality and morbidity risk. “GrimAge2 will not replace existing clinical biomarkers. Rather, GrimAge2 complements existing clinical biomarkers when evaluating an individual’s aging rate.” DOI: https://doi.org/10.18632/aging.204434 Corresponding Author: Steve Horvath - shorvath@mednet.ucla.edu 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 trending research paper published by Aging (Aging-US) in Volume 14, Issue 22, entitled, “Denervation induces mitochondrial decline and exacerbates lysosome dysfunction in middle-aged mice.” ________________________________________________________ A hallmark characteristic of aging is the progressive loss of skeletal muscle mass, known as sarcopenia. A process called motor neuron denervation (Den)—when nerve signals to muscles are blocked or reduced—leads to muscle atrophy, fatigue and eventually muscle loss. Determining how and when Den events influence older muscles is crucially important for developing interventions to stop or reverse age-related muscle wasting. “Further, aged muscle exhibits reduced plasticity to both enhanced and suppressed contractile activity. It remains unclear when the onset of this blunted response occurs, and how middle-aged muscle adapts to denervation.” Dysfunctional mitochondria in muscle tissue are known to increase with age. Lysosomes are responsible for the recycling of damaged mitochondria. However, as muscles age, lysosomal function in muscle tissue also declines. In a new study, researchers Matthew Triolo, Debasmita Bhattacharya and David A. Hood from York University in Toronto, Canada, aimed to characterize the time-dependent changes in denervated skeletal muscle from middle-aged mice. The team focussed on how mitochondrial turnover is impacted. On November 4, 2022, their research paper was published in Aging’s Volume 14, Issue 22, entitled, “Denervation induces mitochondrial decline and exacerbates lysosome dysfunction in middle-aged mice.” Full blog - https://aging-us.org/2022/12/new-insights-into-the-mechanisms-of-sarcopenia/ DOI - https://doi.org/10.18632/aging.204365 Corresponding author - David A. Hood - dhood@yorku.ca Video - https://www.youtube.com/watch?v=Vcrv4KeFvsY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204365 Keywords - mitochondrial biogenesis, autophagy, mitophagy, lysosomes, muscle 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/ 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 14, Issue 22, entitled, “The potential benefit of metformin to reduce delirium risk and mortality: a retrospective cohort study.” Metformin has been reported to improve age-related disorders, including dementia, and to lower mortality. This study was conducted to investigate whether metformin use lowers delirium risk, as well as long-term mortality. In the current retrospective cohort study, researchers Takehiko Yamanashi, Zoe-Ella EM Anderson, Manisha Modukuri, Gloria Chang, Tammy Tran, Pedro S. Marra, Nadia E. Wahba, Kaitlyn J. Crutchley, Eleanor J. Sullivan, Sydney S. Jellison, Katie R. Comp, Cade C. Akers, Alissa A. Meyer, Sangil Lee, Masaaki Iwata, Hyunkeun R. Cho, Eri Shinozaki, and Gen Shinozaki from Stanford University School of Medicine, University of Iowa Carver College of Medicine, University of Iowa College of Public Health, and Tottori University Faculty of Medicine analyzed 1,404 previously recruited subjects. The relationship between metformin use and delirium, and the relationship between metformin use and 3-year mortality were investigated. “Thus, in this report we aimed to investigate the relationship between DM [diabetes mellitus] and delirium risk with a focus on the influence from metformin. We hypothesized that history of metformin use is associated with lower risk for delirium. We were also interested in testing if history of metformin use can alter one of the most important patient outcomes, mortality.” 242 subjects were categorized into a type 2 diabetes mellitus (DM)-without-metformin group, and 264 subjects were categorized into a DM-with-metformin group. Prevalence of delirium was 36.0% in the DM-without-metformin group, and 29.2% in the DM-with-metformin group. A history of metformin use reduced the risk of delirium in patients with DM (OR, 0.50 [95% CI, 0.32 to 0.79]) after controlling for confounding factors. The 3-year mortality in the DM-without-metformin group (survival rate, 0.595 [95% CI, 0.512 to 0.669]) was higher than in the DM-with-metformin group (survival rate, 0.695 [95% CI, 0.604 to 0.770]) (p=0.035). A history of metformin use decreased the risk of 3-year mortality after adjustment for confounding factors (HR, 0.69 [95% CI, 0.48 to 0.98]). The researchers concluded that metformin use may lower the risk of delirium and mortality in DM patients. “In this report, we showed the potential benefit of metformin in decreasing the risk of delirium and mortality in DM subjects.” DOI: https://doi.org/10.18632/aging.204393 Corresponding Author: Gen Shinozaki - gens@stanford.edu Keywords: delirium, metformin, diabetes mellitus, mortality, aging 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 (Aging-US) Volume 14, Issue 22, entitled, “Glutaminase inhibitors rejuvenate human skin via clearance of senescent cells: a study using a mouse/human chimeric model.” Skin aging caused by various endogenous and exogenous factors results in structural and functional changes to skin components. However, the role of senescent cells in skin aging has not been clarified. In this new study, researchers Kento Takaya, Tatsuyuki Ishii, Toru Asou, and Kazuo Kishi, from the Department of Plastic and Reconstructive Surgery at the Keio University School of Medicine, evaluated the effects of the glutaminase inhibitor BPTES (bis-2-(5-phenylacetamido-1, 3, 4-thiadiazol-2-yl)ethyl sulfide) on human senescent dermal fibroblasts and aged human skin to elucidate the function of senescent cells in skin aging. “[...] we utilized plastic surgery to create an experimental mouse/human chimeric model in which intraoperatively obtained human whole skin layers were transplanted into nude mice using previously described methods [25] and evaluated the anti-aging effects of BPTES on real human skin.” Primary human dermal fibroblasts (HDFs) were induced to senescence by long-term passaging, ionizing radiation, and treatment with doxorubicin, an anticancer drug. Cell viability of HDFs was assessed after BPTES treatment. A mouse/human chimeric model was created by subcutaneously transplanting whole skin grafts from aged humans into nude mice. The model was treated intraperitoneally with BPTES or vehicle for 30 days. Skin samples were collected and subjected to reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting, and histological analysis. BPTES selectively eliminated senescent dermal fibroblasts regardless of the method used to induce senescence; aged human skin grafts treated with BPTES exhibited increased collagen density, increased cell proliferation in the dermis, and decreased aging-related secretory phenotypes, such as matrix metalloprotease and interleukin. These effects were maintained in the grafts 1 month after termination of the treatment. In conclusion, selective removal of senescent dermal fibroblasts can improve the skin aging phenotype, indicating that BPTES may be an effective novel therapeutic agent for skin aging. “In summary, our results indicate that selective clearance of aging dermal fibroblasts by BPTES ameliorates skin senescence-related changes and that aging dermal fibroblasts may play an important role in the skin aging process. Therefore, senescent cell eliminators for aging skin cells may be an effective option for treating skin aging.” DOI: https://doi.org/10.18632/aging.204391 Corresponding Author: Kento Takaya - kento-takaya312@keio.jp Sign up for free Altmetric alerts about this article: https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204391 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

A new research paper was published in Aging (listed as "Aging (Albany NY)" by MEDLINE/PubMed and "Aging-US" by Web of Science) Volume 14, Issue 21, entitled, “Krill oil protects dopaminergic neurons from age-related degeneration through temporal transcriptome rewiring and suppression of several hallmarks of aging.” There is accumulating evidence that interfering with the basic aging mechanisms can enhance healthy longevity. The interventional/therapeutic strategies targeting multiple aging hallmarks could be more effective than targeting one hallmark. While health-promoting qualities of marine oils have been extensively studied, the underlying molecular mechanisms are not fully understood. Lipid extracts from Antarctic krill are rich in long-chain omega-3 fatty acids choline, and astaxanthin. In this new study, researchers Tanima SenGupta, Yohan Lefol, Lisa Lirussi, Veronica Suaste, Torben Luders, Swapnil Gupta, Yahyah Aman, Kulbhushan Sharma, Evandro Fei Fang, and Hilde Nilsen from the University of Oslo, Oslo University Hospital and Akershus University Hospital used C. elegans and human cells to investigate whether krill oil promotes healthy aging. “In a C. elegans model of Parkinson's disease, we show that krill oil protects dopaminergic neurons from aging-related degeneration, decreases alpha-synuclein aggregation, and improves dopamine-dependent behavior and cognition” Krill oil rewires distinct gene expression programs that contribute to attenuating several aging hallmarks, including oxidative stress, proteotoxic stress, senescence, genomic instability, and mitochondrial dysfunction. Mechanistically, krill oil increases neuronal resilience through temporal transcriptome rewiring to promote anti-oxidative stress and anti-inflammation via healthspan regulating transcription factors such as SNK-1. Moreover, krill oil promotes dopaminergic neuron survival through regulation of synaptic transmission and neuronal functions via PBO-2 and RIM-1. “Collectively, krill oil rewires global gene expression programs and promotes healthy aging via abrogating multiple aging hallmarks, suggesting directions for further pre-clinical and clinical explorations.” DOI: https://doi.org/10.18632/aging.204375 Corresponding Author: Hilde Nilsen - hilde.nilsen@medisin.uio.no Video: https://www.youtube.com/watch?v=oucZo5px1YU Keywords: krill oil, aging, healthspan, mitochondrial health, senescence 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