Medicine and Health Sciences Commons^™

Lifespan Benefits For The Combination Of Rapamycin Plus Acarbose And For Captopril In Genetically Heterogeneous Mice., Randy Strong, Richard A Miller, Catherine J Cheng, James F Nelson, Jonathan Gelfond, Shailaja Kesaraju Allani, Vivian Diaz, Angela Olsen Dorigatti, Jonathan Dorigatti, Elizabeth Fernandez, Andrzej Galecki, Brett Ginsburg, Karyn L Hamilton, Martin A Javors, Kerry Kornfeld, Matt Kaeberlein, Suja Kumar, David B Lombard, Marisa Lopez-Cruzan, Benjamin F Miller, Peter Rabinovitch, Peter C. Reifsnyder, Nadia Rosenthal, Molly A. Bogue, Adam B Salmon, Yousin Suh, Eric Verdin, Herbert Weissbach, John Newman, Francesca Maccchiarini, David E. Harrison

Faculty Research 2022

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice …

Lifespan Benefits For The Combination Of Rapamycin Plus Acarbose And For Captopril In Genetically Heterogeneous Mice, Randy Strong, Kerry Kornfeld, Et Al.

2020-Current year OA Pubs

Mice bred in 2017 and entered into the C2017 cohort were tested for possible lifespan benefits of (R/S)-1,3-butanediol (BD), captopril (Capt), leucine (Leu), the Nrf2-activating botanical mixture PB125, sulindac, syringaresinol, or the combination of rapamycin and acarbose started at 9 or 16 months of age (RaAc9, RaAc16). In male mice, the combination of Rapa and Aca started at 9 months and led to a longer lifespan than in either of the two prior cohorts of mice treated with Rapa only, suggesting that this drug combination was more potent than either of its components used alone. In females, lifespan in mice …

The Role Of Leisure Engagement In Fostering Cognition In Aging, Karen Wenzel

All Dissertations

Leisure activities are a major component of healthy aging, associated with reduced risk of cognitive decline and enhanced cognitive function. However, there is wide variation in the conceptualization and measurement of leisure. Specific leisure activities or domains have been studied in association with cognition in aging. More recently, researchers have noted that attributes of the activity, rather than the activity itself, may be significant. This study explored the current state of knowledge regarding attributes of leisure activities that foster cognition in aging. A literature review using PRISMA Scoping Review guidelines identified objectively and subjectively measured attributes of leisure engagement in …

Epigenomic And Other Evidence For Cannabis-Induced Aging Contextualized In A Synthetic Epidemiologic Overview Of Cannabinoid-Related Teratogenesis And Cannabinoid-Related Carcinogenesis, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background: Twelve separate streams of empirical data make a strong case for cannabis-induced accelerated aging including hormonal, mitochondriopathic, cardiovascular, hepatotoxic, immunological, genotoxic, epigenotoxic, disruption of chromosomal physiology, congenital anomalies, cancers including inheritable tumorigenesis, telomerase inhibition and elevated mortality. Methods: Results from a recently published longitudinal epigenomic screen were analyzed with regard to the results of recent large epidemiological studies of the causal impacts of cannabis. We also integrate theoretical syntheses with prior studies into these combined epigenomic and epidemiological results. Results: Cannabis dependence not only recapitulates many of the key features of aging, but is characterized by both age-defining and …

Association Of Leukocyte Telomere Length With Perceived Physical Fatigability, Rain Katz, Emma L Gay, Allison L Kuipers, Joseph H Lee, Lawrence S Honig, Kaare Christensen, Mary F Feitosa, Mary K Wojczynski, Nancy W Glynn, Llfs Research Group

2020-Current year OA Pubs

BACKGROUND: Leukocyte telomere length (LTL) is a potential genomic marker of biological aging, but its relation to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability, but that this association would be attenuated by adjusting for chronological age.

METHODS: Two generations of participants (N = 1997; 309 probands, 1688 offspring) were from the Long Life Family Study (age = 73.7 ± 10.4, range 60-108, 54.4 % women), a longitudinal cohort study of aging. LTL was assayed at baseline. Perceived physical fatigability was measured 8.0 ± 1.1 years …

Effects Of Substance Use Disorder On Oxidative And Antioxidative Stress Markers: A Systematic Review And Meta-Analysis, Thiago Wendt Viola, Rodrigo Orso, Luisa Fossati Florian, Miguel Gomes Garcia, Marco Giovanni Signor Gomes, Eduarda Mascarenhas Mardini, João Paulo Ottolia Niederauer, Aline Zaparte, Rodrigo Grassi-Oliveira

School of Medicine Faculty Publications

Recently, it has been suggested that central and peripheral toxicities identified in persons with substance use disorder (SUD) could be partially associated with an imbalance in reactive oxygen species and antioxidant defenses. We conducted a systematic review and meta-analysis to investigate whether SUD is associated with oxidative stress and to identify biomarkers possibly more affected by this condition. We have included studies that analysed oxidant and antioxidant markers in individuals with SUD caused by stimulants, alcohol, nicotine, opioids, and others (cannabis, inhalants, and polysubstance use). Our analysis showed that persons with SUD show higher oxidant markers and lower antioxidant markers …

Age-Related Changes In Skeletal Muscle Oxygen Utilization: A Review, Maxwell T. Aiken, Sabrina S. Salvatore, Kyle N. Zelenski, Ryan K. Perkins

International Journal of Exercise Science: Conference Proceedings

The cardiovascular and skeletal muscle systems are intrinsically interconnected, sharing the goal of delivering oxygen to metabolically active tissue. Deficiencies within those systems that affect oxygen delivery to working tissues are a hallmark of advancing age. Oxygen delivery and utilization are reflected as muscle oxygen saturation (SmO₂) and may be assessed using near-infrared resonance spectroscopy (NIRS). PURPOSE: This review is intended to provide an update on the current state of literature regarding age-related effects on SmO₂. Furthermore, we attempt to bridge the gap between SmO₂ and associated underlying mechanisms affected by aging. FINDINGS: SmO …

Circulating Microrna Responses To Acute Whole-Body Vibration And Resistance Exercise In Postmenopausal Women, Samuel R. Buchanan, Ryan M. Miller, Michelle Nguyen, Christopher D. Black, J. Mikhail Kellawan, Michael G. Bemben, Debra A. Bemben

Health & Human Performance Faculty Publications and Presentations

Evaluating alterations in circulating microRNA (c-miRNA) expression may provide deeper insight into the role of exercise in the attenuation of the negative effects of aging on musculoskeletal health. Currently, there are sparse data on c-miRNA responses to acute exercise in postmenopausal women. The purpose of this study was to characterize the effects of acute bouts of resistance exercise and whole-body vibration on expression of selected c-miRNAs in postmenopausal women aged 65-76 years (n=10). We also examined relationships between c-miRNAs and muscle strength and bone characteristics. This randomized crossover design study compared c-miRNA responses to a bout of resistance exercise (RE) …

Impact Of Sociodemographic Features And Lifestyle On Cognitive Performance Of Peruvian Adults, Brenda Chino, Jonathan Zegarra-Valdivia, Jaisalmer De Frutos-Lucas, Carmen Paredes-Manrique, Nilton Custodio

Research outputs 2022 to 2026

Background:

Cognitive impairment and dementia may result from a combination of modifiable and nonmodifiable risk and protective factors, such as the environment, educational attainment, time devoted to cognitively stimulating activities, and physical activity.

Objective:

This study aimed to investigate the mediating role of sociodemographic characteristics and lifestyle factors in the years of education and cognitive performance in Peruvian adults.

Methods:

This cross-sectional study included 1,478 subjects assessed by Addenbrooke’s Cognitive Examination Revised (ACE-R). Using mediation models, we evaluated the mediation role of parents’ educational level, reading time (RT), and physical activity time (PAT) in the years of education (IYE) and …

The Effects Of Acute High-Intensity Interval Exercise And Hyperinsulinemic-Euglycemic Clamp On Osteoglycin Levels In Young And Middle-Aged Men, Carlie Bauer, Alexander Tacey, Andrew Garnham, Cassandra Smith, Mary N. Woessner, Xuzhu Lin, Navabeh Zarekookandeh, David L. Hare, Joshua R. Lewis, Lewan Parker, Itamar Levinger

Research outputs 2022 to 2026

Osteoglycin (OGN) is a leucine-rich proteoglycan that has been implicated in the regulation of glucose in animal models. However, its relationship with glucose control in humans is unclear. We examined the effect of high-intensity interval exercise (HIIE) and hyperinsulinemic-euglycemic clamp on circulating levels of OGN as well as whether circulating OGN levels are associated with markers of glycemic control and cardio-metabolic health. Serum was analyzed for OGN (ELISA) levels from 9 middle-aged obese men (58.1 ± 2.2 years, body mass index [BMI] = 33.1 ± 1.4 kg∙m ^{− 2}, mean ± SEM) and 9 young men (27.8 ± 1.6 …

Predictive Power Of 24-H Ambulatory Pulse Pressure And Its Components For Mortality And Cardiovascular Outcomes In 11 848 Participants Recruited From 13 Populations, Benjamin Gavish, Michael Bursztyn, Lutgarde Thijs, Dong-Mei Wei, Jesus Melgarejo, Zhen-Yu Zhang, José Boggia, Tine W. Hansen, Kei Asayama, Gladys E. Maestre

School of Medicine Publications and Presentations

Background:

The role of pulse pressure (PP) ‘widening’ at older and younger age as a cardiovascular risk factor is still controversial. Mean PP, as determined from repeated blood pressure (BP) readings, can be expressed as a sum of two components: ‘elastic PP’ (elPP) and ‘stiffening PP’ (stPP) associated, respectively, with stiffness at the diastole and its relative change during the systole. We investigated the association of 24-h ambulatory PP, elPP, and stPP (‘PP variables’) with mortality and composite cardiovascular events in different age classes.

Method:

Longitudinal population-based cohort study of adults with baseline observations that included 24-h ambulatory BP. Age …

Covariance-Based Vs. Correlation-Based Functional Connectivity Dissociates Healthy Aging From Alzheimer Disease, Jeremy F. Strain, Matthew R. Brier, Aaron Tanenbaum, Brian A. Gordon, John E. Mccarthy, Aylin Dincer, Daniel S. Marcus, Richard J. Perrin, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances, Abraham Z. Snyder, Et Al.

2020-Current year OA Pubs

Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched …

Commentary: Examining Contextual Factors Contributing To Differentials In Covid-19 Mortality In U.S. Vs. India., Preeti Zanwar, Katrine L Wallace, Christopher Soria, Arokiasamy Perianayagam

College of Population Health Faculty Papers

No abstract provided.

Transcriptional Profiles In Olfactory Pathway-Associated Brain Regions Of African Green Monkeys: Associations With Age And Alzheimer’S Disease Neuropathology, Jacob D Negrey, Dorothy L Dobbins, Timothy D Howard, Karin E Borgmann-Winter, C G Hahn, Sergey Kalinin, Douglas L Feinstein, Suzanne Craft, Carol A Shively, Thomas C Register

Department of Neuroscience Faculty Papers

Introduction: Olfactory impairment in older individuals is associated with an increased risk of Alzheimer's disease (AD). Characterization of age versus neuropathology-associated changes in the brain olfactory pathway may elucidate processes underlying early AD pathogenesis. Here, we report age versus AD neuropathology-associated differential transcription in four brain regions in the olfactory pathway of 10 female African green monkeys (vervet, Chlorocebus aethiops sabaeus), a well-described model of early AD-like neuropathology.

Methods: Transcriptional profiles were determined by microarray in the olfactory bulb (OB), piriform cortex (PC), temporal lobe white matter (WM), and inferior temporal cortex (ITC). Amyloid beta (Aβ) plaque load in …

Marijuana Use And Dna Methylation-Based Biological Age In Young Adults, Drew R Nannini, Yinan Zheng, Brian T Joyce, Tao Gao, Lei Liu, David R Jacobs Jr, Pamela Schreiner, Chunyu Liu, Steve Horvath, Ake T Lu, Kristine Yaffe, Stephen Sidney, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou

2020-Current year OA Pubs

BACKGROUND: Marijuana is the third most commonly used drug in the USA and efforts to legalize it for medical and recreational use are growing. Despite the increase in use, marijuana's effect on aging remains understudied and understanding the effects of marijuana on molecular aging may provide novel insights into the role of marijuana in the aging process. We therefore sought to investigate the association between cumulative and recent use of marijuana with epigenetic age acceleration (EAA) as estimated from blood DNA methylation.

RESULTS: A random subset of participants from The Coronary Artery Risk Development in Young Adults (CARDIA) Study with …

Variability In Energy Expenditure Is Much Greater In Males Than Females, Lewis G Halsey, Susan B Racette, Et Al.

2020-Current year OA Pubs

In mammals, trait variation is often reported to be greater among males than females. However, to date, mainly only morphological traits have been studied. Energy expenditure represents the metabolic costs of multiple physical, physiological, and behavioral traits. Energy expenditure could exhibit particularly high greater male variation through a cumulative effect if those traits mostly exhibit greater male variation, or a lack of greater male variation if many of them do not. Sex differences in energy expenditure variation have been little explored. We analyzed a large database on energy expenditure in adult humans (1494 males and 3108 females) to investigate whether …

The Intersection Between Toxicology And Aging Research: A Toxic Aging Coin Perspective., John P. Wise Jr.

Faculty Scholarship

We are imminently faced with the challenges of an increasingly aging population and longer lifespans due to improved health care. Concomitantly, we are faced with ubiquitous environmental pollution linked with various health effects and age-related diseases which contribute to increased morbidity with age. Geriatric populations are rarely considered in the development of environmental regulations or in toxicology research. Today, life expectancy is often into one’s 80s or beyond, which means multiple decades living as a geriatric individual. Hence, adverse health effects and late-onset diseases might be due to environmental exposures as a geriatric, and we currently have no way of …

The Effect Of Exercise Modality On Age-Related Changes Observed During Running, Brianne Borgia, Janet S. Dufek, Kara N. Radzak, Julia Freedman Silvernail

Kinesiology and Nutrition Sciences Faculty Publications

Introduction: With the increase in participation by older adults in endurance events, research is needed to evaluate how exercising throughout the lifespan can afect the aging process regarding gait and mobility. The purpose of this study was to determine how the type of exercise modality one participates in will affect age-related declines observed during running.

Methods: Fifty-six individuals between the ages of 18–65 who considered running, resistance training or cycling/ swimming as their primary form of activity participated in this study. Kinematics were captured using a 10-camera motion capture system while participants ran at a controlled pace of 3.5 m/s …

Role Of Sirtuins In Diabetes And Age-Related Processes., Nimisha Lingappa, Harvey N Mayrovitz

HPD Articles

The practice of intermittent fasting continues to grow as a widely practiced diet trend due to its feasibility and reported high success rate. By practicing intermittent fasting, levels of sirtuin proteins (SIRTs), also known as the longevity protein, rise in the body and bring numerous health benefits. Currently, seven SIRTs have been described in humans in different locations of the cell with a wide variety of corresponding functions including gene transcription, DNA repair, and protection against oxidative damage. SIRT activators, such as resveratrol found in red wine, are also commonly consumed to amplify the health benefits associated with protection against …

Neuroanatomy In Mild Cognitive Impairment: Relationship To Functional Skills, Treatment Expectancy, And Comorbid Depression, Sara Rushia

Dissertations, Theses, and Capstone Projects

Mild cognitive impairment (MCI) is a neurocognitive disorder defined by cognitive decline in older adults. Although MCI has been studied for decades, there remain important areas to be explored in order to adequately characterize aspects of this disorder that provide information valuable for possible interventions and disease progression to dementia, including a better understanding of the neuroanatomical variables relevant to this disorder. Such neuroanatomical variables include cortical thickness, hippocampal volume, and white matter hyperintensities (WMHs). This dissertation consists of three separate studies aimed at addressing gaps in the literature on MCI in relation to brain morphometrics and under-studied characteristics involved …

Resilience: Key Factors Associated With Resilience Of Older People In Botswana, Magen Mhaka-Mutepfa, Sheila Shaibu

School of Nursing & Midwifery, East Africa

This study aims to determine key factors that predict resilience in older people. A cross-sectional design and quantitative methods were used for this study. Four districts were selected in Botswana using cluster random sampling. Data on resilience from 378 older adults aged 60 years+ [Mean Age (SD) = 71.1(9.0)] was collected using snowballing technique. Data on socio-demographics, protective and risk factors were also collected from urban and rural areas. CHAID (Chi-squared Automatic Interaction Detection) analysis was used to predict the strengths of the relationships among resilience and all predictor variables because the data were skewed. Five major predictor …

Abdominal Aortic Calcification On Lateral Spine Images Captured During Bone Density Testing And Late-Life Dementia Risk In Older Women: A Prospective Cohort Study, Tenielle Porter, Marc Sim, Richard L. Prince, John T. Schousboe, Catherine Bondonno, Wai H. Lim, Kun Zhu, Douglas P. Kiel, Jonathan M. Hodgson, Simon M. Laws, Joshua R. Lewis

Research outputs 2022 to 2026

Background: Dementia after the age of 80 years (late-life) is increasingly common due to vascular and non-vascular risk factors. Identifying individuals at higher risk of late-life dementia remains a global priority. Methods: In prospective study of 958 ambulant community-dwelling older women ( ≥ 70 years), lateral spine images (LSI) captured in 1998 (baseline) from a bone density machine were used to assess abdominal aortic calcification (AAC). AAC was classified into established categories (low, moderate and extensive). Cardiovascular risk factors and apolipoprotein E (APOE) genotyping were evaluated. Incident 14.5-year late-life dementia was identified from linked hospital and mortality records. Findings: At …

Disease Burden Affects Aging Brain Function, Lori L Beason-Held, Danielle Fournier, Andrea T Shafer, Elisa Fabbri, Yang An, Chiung-Wei Huang, Murat Bilgel, Dean F Wong, Luigi Ferrucci, Susan M Resnick

2020-Current year OA Pubs

BACKGROUND: Most older adults live with multiple chronic disease conditions, yet the effect of multiple diseases on brain function remains unclear.

METHODS: We examine the relationship between disease multimorbidity and brain activity using regional cerebral blood flow (rCBF) 15O-water PET scans from 97 cognitively normal participants (mean baseline age 76.5) in the Baltimore Longitudinal Study of Aging (BLSA). Multimorbidity index scores, generated from the presence of 13 health conditions, were correlated with PET data at baseline and in longitudinal change (n = 74) over 5.05 (2.74 SD) years.

RESULTS: At baseline, voxel-based analysis showed that higher multimorbidity scores were associated …

Functional Neuroimaging Techniques To Examine Falls And Cognition In Older Adults: A Systematic Review, Tia M. Seleem, Raphael Gabiazon

Undergraduate Student Research Internships Conference

Falls in older adults have been attributed to impaired cognition. There is potential for neuroimaging techniques to understand the biological components that are involved in the cognitive processes pertaining to falls. Therefore, the purpose of this systematic review was to analyze how functional neuroimaging can be used to examine the relationship between falls and cognition among older adults. The following five electronic databases were selected to identify peer-reviewed articles in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: 1) Medline (via OVID), 2) PsycINFO (via OVID), 3) CINAHL (via EBSCO), 4) EMBASE (via OVID), and 5) Pubmed. …

Normal Aging In Mice Is Associated With A Global Reduction In Cortical Spectral Power And Network-Specific Declines In Functional Connectivity, Asher J Albertson, Eric C Landsness, Michelle J Tang, Ping Yan, Hanyang Miao, Zachary P Rosenthal, Byungchan Kim, Joseph C Culver, Adam Q Bauer, Jin-Moo Lee

2020-Current year OA Pubs

Normal aging is associated with a variety of neurologic changes including declines in cognition, memory, and motor activity. These declines correlate with neuronal changes in synaptic structure and function. Degradation of brain network activity and connectivity represents a likely mediator of age-related functional deterioration resulting from these neuronal changes. Human studies have demonstrated both general decreases in spontaneous cortical activity and disruption of cortical networks with aging. Current techniques used to study cerebral network activity are hampered either by limited spatial resolution (e.g. electroencephalography, EEG) or limited temporal resolution (e.g., functional magnetic resonance imaging, fMRI). Here we utilize mesoscale imaging …

A Smartwatch Step-Counting App For Older Adults: Development And Evaluation Study, George Boateng, Curtis L. Petersen, David Kotz, Karen L. Fortuna, Rebecca Masutani, John A. Batsis

Dartmouth Scholarship

Background: Older adults who engage in physical activity can reduce their risk of mobility impairment and disability. Short amounts of walking can improve quality of life, physical function, and cardiovascular health. Various programs have been implemented to encourage older adults to engage in physical activity, but sustaining their motivation continues to be a challenge. Ubiquitous devices, such as mobile phones and smartwatches, coupled with machine-learning algorithms, can potentially encourage older adults to be more physically active. Current algorithms that are deployed in consumer devices (eg, Fitbit) are proprietary, often are not tailored to the movements of older adults, and have …

The Intersectionality Of Stuttering And Aging, Mary Elizabeth Herring

University Honors Theses

The purpose of this study is to explore relationships between stuttering and aging so that speech-language pathologists can be informed about the intersectionality of these identities.

Three adult men who stutter, all over the age of 65, were interviewed in semi-structured interviews. Interview transcripts were analyzed with in-vivo coding to find codes and themes between participants. From the interviews, 20 categories were identified. These categories were then funneled into four overarching themes: 1) Personal factors impacted by stuttering, 2) Stuttering perspectives across the lifespan, 3) Stuttering therapy experiences, and 4) Covert stuttering.

This study shows that attitudes, perspectives, and experiences …

The Coping Strategies Of Older Adults With Age Related Vision Loss (Arvl) – A Narrative Account, Zakara J. Stampp

Electronic Thesis and Dissertation Repository

The goal of this study was to share the stories of older adults with age-related vision loss (ARVL) and how they have coped to maintain meaningful occupational engagement. Grounded in a constructivist paradigm, data collection and analysis were guided by the narrative inquiry methodology. The participants consisted of six older adults aged 60 or older, diagnosed with one of the following ARVL conditions: macular degeneration, diabetic retinopathy, and/or glaucoma. Participants were recruited from vision loss non-profit organizations such as the Canadian National Institute for the Blind (CNIB) and the Alliance for Equity of Blind Canadians (AEBC). One older adult was …

Stromal Vascular Fraction Restores Vasodilatory Function By Reversing Mitochondrial Dysfunction And Oxidative Stress In Aging-Induced Coronary Microvascular Disease., Evan Paul Tracy

Electronic Theses and Dissertations

Background: Coronary Microvascular Disease (CMD) presents in aging post-menopausal women with chronic angina due to microvascular hyperconstriction. The objective was to identify mechanisms of adipose stromal vascular fraction’s (SVF) restorative effects on vasodilation. We hypothesize aging-induced CMD is caused by a) abrogated flow-mediated dilation (FMD) due to loss of nitric oxide signaling and b) ROS-dependent βADR desensitization & internalization, reversible by ameliorating mitochondrial dysfunction and oxidative stress with SVF. Methods: Coronary microvessels were isolated from female rats either young, old, or old with SVF tail-vein injection (OSVF). Pressure myography, RNA-sequencing, immunofluorescence, Western blotting, and morphological analysis were performed to …

Slc12a8 In The Lateral Hypothalamus Maintains Energy Metabolism And Skeletal Muscle Functions During Aging, Naoki Ito, Ai Takatsu, Hiromi Ito, Yuka Koike, Kiyoshi Yoshioka, Yasutomi Kamei, Shin-Ichiro Imai

2020-Current year OA Pubs

Sarcopenia and frailty are urgent socio-economic problems worldwide. Here we demonstrate a functional connection between the lateral hypothalamus (LH) and skeletal muscle through Slc12a8, a recently identified nicotinamide mononucleotide transporter, and its relationship to sarcopenia and frailty. Slc12a8-expressing cells are mainly localized in the LH. LH-specific knockdown of Slc12a8 in young mice decreases activity-dependent energy and carbohydrate expenditure and skeletal muscle functions, including muscle mass, muscle force, intramuscular glycolysis, and protein synthesis. LH-specific Slc12a8 knockdown also decreases sympathetic nerve signals at neuromuscular junctions and β2-adrenergic receptors in skeletal muscle, indicating the importance of the LH-sympathetic nerve-β2-adrenergic receptor axis. LH-specific overexpression …