Aging-US

A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 16, entitled, “Reorganization of pancreas circadian transcriptome with aging.” The evolutionarily conserved circadian system allows organisms to synchronize internal processes with 24-h cycling environmental timing cues, ensuring optimal adaptation. Like other organs, the pancreas function is under circadian control. Recent evidence suggests that aging by itself is associated with altered circadian homeostasis in different tissues which could affect the organ’s resiliency to aging-related pathologies. Pancreas pathologies of either endocrine or exocrine components are age-related. Whether pancreas circadian transcriptome output is affected by age is still unknown. In their new study, researchers Deepak Sharma, Caitlin R. Wessel, Mahboobeh Mahdavinia, Fabian Preuss, and Faraz Bishehsari from Rush University and University of Wisconsin-Parkside profiled the impact of age on the pancreatic transcriptome over a full circadian cycle and elucidated a circadian transcriptome reorganization of pancreas by aging. “Here we carried out a 24-h circadian transcriptomic analysis of pancreas from male mice at young and old ages.” The researchers defined a comprehensive circadian transcriptome landscape and identified biological pathways that are reflective of aging pancreas. Additionally, analysis of the pancreatic microenvironment revealed novel mechanistic insights into the fibroblast-mediated regulation of rhythmicity in aged pancreas. The team suggests that the circadian transcriptome in aging pancreas re-organizes in response to age-specific signals from the cellular microenvironment, primarily modulated by fibroblasts. “Our study highlights gain of rhythms in the extrinsic cellular pathways in the aged pancreas and extends a potential role to fibroblast-associated mechanisms.” DOI - https://doi.org/10.18632/aging.204929 Corresponding author - Faraz Bishehsari - Faraz_Bishehsari@rush.edu Video short - https://www.youtube.com/watch?v=dhHK8udB1eg Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204929 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, circadian rhythms, RNA transcriptomics, pancreas 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/@AgingJournal 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 (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 16, entitled, “Dectin-1 stimulation promotes a distinct inflammatory signature in the setting of HIV-infection and aging.” Dectin-1 is an innate immune receptor that recognizes and binds β-1, 3/1, 6 glucans on fungi. In this new study, researchers Archit Kumar, Jiawei Wang, Allen Esterly, Chris Radcliffe, Haowen Zhou, Brent Vander Wyk, Heather G. Allore, Sui Tsang, Lydia Barakat, Subhasis Mohanty, Hongyu Zhao, Albert C. Shaw, and Heidi J. Zapata evaluated Dectin-1 function in myeloid cells in a cohort of HIV-positive and HIV-negative young and older adults. “The HIV-positive and HIV-negative groups were comparable in age and gender distribution, incidence of comorbidities such as diabetes, metabolic syndrome, cardiovascular disease and pulmonary disease.” Stimulation of monocytes with β-D-glucans induced a pro-inflammatory phenotype in monocytes of HIV-infected individuals that was characterized by increased levels of IL-12, TNF-α, and IL-6, with some age-associated cytokine increases also noted. Dendritic cells showed a striking HIV-associated increase in IFN-α production. These increases in cytokine production paralleled increases in Dectin-1 surface expression in both monocytes and dendritic cells that were noted with both HIV and aging. Differential gene expression analysis showed that HIV-positive older adults had a distinct gene signature compared to other cohorts characterized by a robust TNF-α and coagulation response (increased at baseline), a persistent IFN-α and IFN-γ response, and an activated dendritic cell signature/M1 macrophage signature upon Dectin-1 stimulation. Dectin-1 stimulation induced a strong upregulation of MTORC1 signaling in all cohorts, although increased in the HIV-Older cohort (stimulation and baseline). In sum, this study demonstrates that the HIV Aging population has a distinct immune signature in response to Dectin-1 stimulation. This signature may contribute to the pro-inflammatory environment that is associated with HIV and aging. “Overall, this study demonstrates that age, HIV-infection and co-morbidities can alter the individual immune response. In particular our study showed a unique immune signature in the setting of both HIV and aging in response to Dectin-1 stimulation.” DOI - https://doi.org/10.18632/aging.204927 Corresponding author - Heidi J. Zapata - heidi.zapata@yale.edu Video short - https://www.youtube.com/watch?v=MpMBDvv0dDI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204927 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, immune response, innate immune cells, HIV-infection, dectin-1 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 15, entitled, “Epigenetic aging in oocytes.” Aging-related phenotypes span many different tissues and cell types, and start to occur at different ages - a different typical age for every cell type. In their new editorial, researchers Peera Wasserzug-Pash and Michael Klutstein from The Hebrew University of Jerusalem discuss one of the earliest occurring aging events in the human body, which is the beginning of female reproductive aging and deterioration. The clinical cut-off for advanced maternal age (AMA), a condition associated with poor reproductive outcomes, is 35 years old. “The early onset of reproductive aging poses a significant challenge to clinicians since a global consistent increase in maternal age at first birth has occurred in recent decades, effectively shortening the available time window for reproduction [1].” As the rate of patients with advanced maternal age rises, and with it, the number of patients in fertility clinics, so does the necessity for a fundamental understanding of the reproductive aging process. In recent years, it has been established that there is a substantial dominating influence of oocyte quality loss on age-related fertility decline. This is best demonstrated by the rise in IVF success rates in reproductively aged women when they receive an egg donation from a younger woman. Oocyte quality loss is characterized by diminished cellular function and an increased occurrence of chromosomal nondisjunctions. “Our recent publication [4] addresses the question of additional, epigenetic mechanisms that lead to the occurrence of age-related oocyte quality loss.” DOI - https://doi.org/10.18632/aging.204976 Corresponding author - Michael Klutstein - michaelk@ekmd.huji.ac.il Video short - https://www.youtube.com/watch?v=KHOVKKaJykY&t=45s Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204976 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, oocytes, heterochromatin, epigenetics, maturation 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

The lacrimal gland, found in the upper outer part of the eye’s hollow area, is an important gland that makes tears to protect the eye from infections. It’s split into two parts: one near the inside of the eyelid that can be seen when the eyelid is flipped, and another part with ducts lower in the eye that connects to its counterpart. In their fully functioning status, these ducts release fluid onto the surface of the eye. As humans age (especially women), the lacrimal gland gradually becomes infiltrated by aberrant immune cells and can ultimately lead to an uncomfortable condition known as dry eye disease. “Burning and redness in the eyes, grittiness and blurry vision make life miserable and currently, eye drops with a variety of lubricant components and in the most severe cases, immunosuppressors, are the only therapies approved for this disease.” In a well-written new editorial paper, researchers Claudia M. Trujillo-Vargas and Cintia S. de Paiva from the Department of Ophthalmology at Baylor College of Medicine artfully discuss their recent studies which shed light on the immune system’s role in dry eye disease. On August 11, 2023, their editorial was published in Aging’s Volume 15, Issue 15, entitled, “Our search of immune invaders in the aged lacrimal gland.” Full blog - https://aging-us.org/2023/08/dry-eyes-it-may-be-immune-infiltration-in-aging-lacrimal-glands/ Paper DOI - https://doi.org/10.18632/aging.204651 Corresponding author - Cintia S. de Paiva - cintiadp@bcm.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204651 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, lacrimal gland, ectopic lymphoid structures, immune invasion 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/@AgingJournal 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 15, Issue 15, entitled, “Cardiovascular events and death after catheter ablation in very old patients with nonvalvular atrial fibrillation.” Catheter ablation of atrial fibrillation (AF) is recommended for selected older patients. However, the preventive effects of AF ablation on cardiovascular events and death remain unclear, especially in older patients. In this new study, researchers Keisuke Okawa, Satoshi Taya, Takeshi Morimoto, Ryu Tsushima, Yuya Sudo, Ai Sakamoto, Eisuke Saito, Masahiro Sogo, Masatomo Ozaki, and Masahiko Takahashi from Kagawa Prefectural Central Hospital and Hyogo Medical University aimed to investigate the impact of AF ablation on the incidence of cardiovascular events and death in very old nonvalvular AF (NVAF) patients. “We conducted a prospective cohort study of consecutive patients with NVAF aged ≥80 years and using direct oral anticoagulants (DOACs).” The researchers defined cardiovascular events as acute heart failure (AHF), strokes and systemic embolisms (SSEs), acute coronary syndrome (ACS), and sudden cardiac death (SCD) and cardiovascular death as AHF/SSE/ACS-related death and SCD. They compared the 3-year incidence of cardiovascular events and death between the patients who underwent AF ablation (Ablation group) and those who received medical therapy only (Medication group). Among the 782 NVAF patients using DOACs, propensity score matching provided 208 patients in each group. The Ablation group had a significantly lower 3-year incidence of cardiovascular events and death than the Medication group: cardiovascular events, 24 (13.2%) vs. 43 (23.3%), log-rank P = 0.009 and hazard ratio (HR) 0.52 (95% confidence interval (CI) 0.32–0.86) and cardiovascular deaths, 5 (3.0%) vs. 15 (7.8%), log-rank P = 0.019 and HR 0.32 (95% CI 0.16–0.88). “In very old NVAF patients using DOACs, those who underwent AF ablation had a lower incidence of both cardiovascular events and death than those who received medical therapy only.” DOI - https://doi.org/10.18632/aging.204952 Corresponding author - Keisuke Okawa - k-ookawa@chp-kagawa.jp Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204952 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, atrial fibrillation, catheter ablation, cardiovascular event, cardiovascular death, very old patient 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/@AgingJournal 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 by Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) in Volume 15, Issue 15, entitled, “Associations between klotho and telomere biology in high stress caregivers.” Aging biomarkers may be related to each other through direct co-regulation and/or through being regulated by common processes associated with chronological aging or stress. Klotho is an aging regulator that acts as a circulating hormone with critical involvement in regulating insulin signaling, phosphate homeostasis, oxidative stress, and age-related inflammatory functioning. In this new study, researchers Ryan L. Brown, Elissa E. Epel, Jue Lin, Dena B. Dubal, and Aric A. Prather from the Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, Department of Biochemistry and Biophysics, University of California, San Francisco, and the Department of Neurology and Weill Institute of Neurosciences, University of California, San Francisco discuss the association between klotho levels and telomere length of specific sorted immune cells among a healthy sample of mothers caregiving for a child with autism spectrum disorder (ASD) or a child without ASD - covarying age and body mass index - in order to understand if high stress associated with caregiving for a child with an ASD may be involved in any association between these aging biomarkers. “Here we examine the relationship between two important biomarkers of aging, klotho and telomere length, in a healthy sample stratified into groups based on a combination of (a) stressor exposure and (b) level of perceived stress (i.e., high-stress mothers of children with ASD compared to low-stress mothers of neurotypical children).” In 178 caregiving women, the researchers found that klotho levels were positively associated with telomere length in PBMCs (an effect driven by CD4+ and CD8+CD28− T cells) among high-stress mothers of children with an ASD, but not among low-stress mothers of neurotypical children. There were no significant associations between klotho and telomerase activity in either group, across cell types assessed here. “Our results suggest that klotho levels and telomere length may be associated through a coordinated downregulation of longevity factors occurring under higher stress caregiving conditions.” DOI - https://doi.org/10.18632/aging.204961 Corresponding author - Ryan L. Brown - ryan.brown@ucsf.edu Video short - https://www.youtube.com/watch?v=y0P4vsf1IIk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204961 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, aging biology, stress, klotho, telomeres, telomerase 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/@AgingJournal 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 15, entitled, “Natural aging and ovariectomy induces parallel phosphoproteomic alterations in skeletal muscle of female mice.” The loss of skeletal muscle strength mid-life in females is associated with the decline of estrogen. In this new study, researchers Mina P. Peyton, Tzu-Yi Yang, LeeAnn Higgins, Todd W. Markowski, Kevin Murray, Cha Vue, Laurie L. Parker, and Dawn A. Lowe from the University of Minnesota questioned how estrogen deficiency might impact the overall skeletal muscle phosphoproteome after contraction, as force production induces phosphorylation of several muscle proteins. “Importantly, identification of these altered phosphosites and candidate kinases and phosphatases sensitive to the presence of estrogen will help advance our understanding of the contributions of estrogen deficiency to muscle strength loss in aging females.” Phosphoproteomic analyses of the tibialis anterior muscle after contraction in two mouse models of estrogen deficiency, ovariectomy (Ovariectomized (Ovx) vs. Sham) and natural aging-induced ovarian senescence (Older Adult (OA) vs. Young Adult (YA)), identified a total of 2,593 and 3,507 phosphopeptides in Ovx/Sham and OA/YA datasets, respectively. Further analysis of estrogen deficiency-associated proteins and phosphosites identified 66 proteins and 21 phosphosites from both datasets. Of these, 4 estrogen deficiency-associated proteins and 4 estrogen deficiency-associated phosphosites were significant and differentially phosphorylated or regulated, respectively. Comparative analyses between Ovx/Sham and OA/YA using Ingenuity Pathway Analysis (IPA) found parallel patterns of inhibition and activation across IPA-defined canonical signaling pathways and physiological functional analysis, which were similarly observed in downstream GO, KEGG, and Reactome pathway overrepresentation analysis pertaining to muscle structural integrity and contraction, including AMPK and calcium signaling. IPA Upstream regulator analysis identified MAPK1 and PRKACA as candidate kinases and calcineurin as a candidate phosphatase sensitive to estrogen. “In summary, our results from contracted skeletal muscle highlight CAST Ser-82 as a candidate phosphosite, and MAPK1/ERK2, PRKACA, and calcineurin as candidate upstream regulators sensitive to estrogen deficiency that may contribute to changes in the force-generating capacity of skeletal muscle.” DOI - https://doi.org/10.18632/aging.204959 Corresponding author - Dawn A. Lowe - lowex017@umn.edu Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204959 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, estrogen deficiency, CAST, MAPK, PKA, calcineurin 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

A new editorial paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 14, entitled, “A novel theory of ageing independent of damage accumulation.” The underlying cause or causes of aging are an enduring mystery, but in 1977 Kirkwood postulated that organisms might gain a fitness advantage by reducing investment in somatic maintenance if this allowed them to invest more resources in more crucial processes such as reproduction. The accumulation of somatic damage was therefore inevitable, and his disposable soma theory has dominated gerontology ever since. However, as our understanding of aging increases, it is becoming increasingly difficult to align all the aspects of aging with accumulating damage. For example, mutations that increase damage accumulation can also increase longevity, while rejuvenation revelations such as parabiosis and Yamanaka factors indicate that youthfulness can be regained without high energetic cost and despite high levels of damage. In their new editorial, researchers James Wordsworth and Daryl Shanley from Newcastle University discuss their recently published paper on selective destruction theory (SDT). SDT suggests a mechanism of aging which is both independent of accumulating damage and consistent with epigenetic rejuvenation. The authors used agent-based modeling to describe how aging could undergo positive selection independent of energetic costs. “The mechanism of selective destruction is currently theoretical. In our most developed model, we demonstrated that if slow cells induced epigenetic changes in faster cells causing their metabolism to slow (rather than killing them) it not only reduced unnecessary cell death, but also further reduced the likelihood of overactivity disorders by preventing the spread of fast cells.” DOI - https://doi.org/10.18632/aging.204956 Corresponding author - James Wordsworth - James.Wordsworth2@newcastle.ac.uk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204956 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, ageing, evolution, damage, cell competition, metabolic slowdown 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/@AgingJournal 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 15, Issue 14, entitled, “Inhibiting NLRP3 signaling in aging podocytes improves their life- and health-span.” The decrease in the podocyte’s lifespan and health-span that typify healthy kidney aging cause a decrease in their normal structure, physiology and function. The ability to halt and even reverse these changes becomes clinically relevant when disease is superimposed on an aged kidney. NLRP3 [nod-like receptor protein 3] expression is increased in podocytes of mice with advanced age and contributes to their damage. “However, the functional consequence of increased levels of NLRP3 in aged podocytes is unknown.” In this new study, researchers Natalya Kaverina, R. Allen Schweickart, Gek Cher Chan, Joseph C. Maggiore, Diana G. Eng, Yuting Zeng, Sierra R. McKinzie, Hannah S. Perry, Adilijiang Ali, Christopher O’Connor, Beatriz Maria Veloso Pereira, Ashleigh B. Theberge, Joshua C. Vaughan, Carol J. Loretz, Anthony Chang, Neil A. Hukriede, Markus Bitzer, Jeffrey W. Pippin, Oliver Wessely, and Stuart J. Shankland from the University of Washington, Cleveland Clinic Foundation, National University Hospital Singapore, University of Pittsburgh, University of Michigan, and the University of Chicago hypothesized that reducing NLRP3 signaling earlier at middle-age improves overall podocyte health and slows down healthy podocyte aging in mice. “To this end, we performed a comprehensive analysis of inflammasome signaling including pharmacological and genetic NLRP3 loss-of-function approaches.” RNA-sequencing of podocytes from middle-aged mice showed an inflammatory phenotype with increases in the NLRP3 inflammasome, signaling for IL2/Stat5, IL6 and TNF, interferon gamma response, allograft rejection and complement, consistent with inflammaging. Furthermore, injury-induced NLRP3 signaling in podocytes was further augmented in aged mice compared to young ones. The NLRP3 inflammasome (NLRP3, Caspase-1, IL1β IL-18) was also increased in podocytes of middle-aged humans. Higher transcript expression for NLRP3 in human glomeruli was accompanied by reduced podocyte density and increased global glomerulosclerosis and glomerular volume. Pharmacological inhibition of NLRP3 with MCC950, or gene deletion, reduced podocyte senescence and the genes typifying aging in middle-aged mice, which was accompanied by an improved podocyte lifespan and health-span. Moreover, modeling the injury-dependent increase in NLRP3 signaling in human kidney organoids confirmed the anti-senescence effect of MC9950. Finally, NLRP3 also impacted liver aging. “In summary, our results demonstrate for the first time that aging podocytes acquire an inflammatory phenotype, which include the NLRP3 inflammasome and which is consistent with inflammaging.” DOI - https://doi.org/10.18632/aging.204897 Corresponding authors - Oliver Wessely - wesselo@ccf.org, and Stuart J. Shankland - stuartjs@uw.edu Keywords - aging, kidney, podocyte, NLRP3 inflammasome, reporter 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. Visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ For media inquiries, please contact: MEDIA@IMPACTJOURNALS.COM

A new research perspective was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 14, entitled, “Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases?” In his new research perspective, Dr. Mikhail V. Blagosklonny from Roswell Park Comprehensive Cancer Center discusses aging and rapamycin (Sirolimus) — the only drug that consistently extends life span in countless animal studies in all species tested. He writes that individuals taking rapamycin and those not taking it will ultimately succumb to age-related diseases. However, if administered in disease-oriented dosages for an extended period of time, individuals taking rapamycin may experience a delayed onset of such diseases, and live longer. “The goal is to delay a particular disease that is expected to be life-limiting in a particular person.” Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. Dr. Blagosklonny further discusses the hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself. “I emphasize that aging is not programmed but, in contrast, quasi-programmed. Quasi means pseudo; seemingly; apparently but not really. Some scientists deliberately represent hyperfunction theory as theory of programmed aging. It’s the opposite. Quasi-program is a continuation of a real program. Quasi-program has no intent, no purpose and it is always harmful.” DOI - https://doi.org/10.18632/aging.204920 Corresponding author - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204920 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, mTOR, hyperfunction, lifespan, health span, cancer, Alzheimer’s disease 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/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM