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2. SARS-CoV-2 infection establishes a stable and age-independent CD8+ T cell response against a dominant nucleocapsid epitope using restricted T cell receptors

Author

Choy, Cecily, Chen, Joseph, Li, Jiangyuan, Gallagher, D. Travis, Lu, Jian, Wu, Daichao, Zou, Ainslee, Hemani, Humza, Baptiste, Beverly A., Wichmann, Emily, Yang, Qian, Ciffelo, Jeffrey, Yin, Rui, McKelvy, Julia, Melvin, Denise, Wallace, Tonya, Dunn, Christopher, Nguyen, Cuong, Chia, Chee W., Fan, Jinshui, Ruffolo, Jeannie, Zukley, Linda, Shi, Guixin, Amano, Tomokazu, An, Yang, Meirelles, Osorio, Wu, Wells W., Chou, Chao-Kai, Shen, Rong-Fong, Willis, Richard A., Ko, Minoru S. H., Liu, Yu-Tsueng, De, Supriyo, Pierce, Brian G., Ferrucci, Luigi, Egan, Josephine, Mariuzza, Roy, and Weng, Nan-Ping

Published
2023
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5. Age‐associated expression of p21and p53 during human wound healing

Author

Chia, Chee W, Sherman‐Baust, Cheryl A, Larson, Sara A, Pandey, Ritu, Withers, Roxanne, Karikkineth, Ajoy C, Zukley, Linda M, Campisi, Judith, Egan, Josephine M, Sen, Ranjan, and Ferrucci, Luigi

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Aging, Genetics, Clinical Research, Adult, Aged, Cyclin-Dependent Kinase Inhibitor p16, Cyclin-Dependent Kinase Inhibitor p21, Female, Humans, Male, Pilot Projects, Skin, Tumor Suppressor Protein p53, Wound Healing, aging, human wound healing, p21, p53, Biological Sciences, Medical and Health Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences
Abstract

In mice, cellular senescence and senescence-associated secretory phenotype (SASP) positively contribute to cutaneous wound healing. In this proof-of-concept study, we investigated the expressions of p16, p21, and other senescence-associated biomarkers during human wound healing in 24 healthy subjects using a double-biopsy experimental design. The first punch biopsy created the wound and established the baseline. The second biopsy, concentric to the first and taken several days after wounding, was used to probe for expression of biomarkers by immunohistochemistry and RNA FISH. To assess the effects of age, we recruited 12 sex-matched younger (30.2 ± 1.3 years) and 12 sex-matched older (75.6 ± 1.8 years) subjects. We found that p21 and p53, but not p16, were induced during healing in younger, but not older subjects. A role for Notch signaling in p21 expression was inferred from the inducible activation of HES1. Further, other SASP biomarkers such as dipeptidyl peptidase-4 (DPP4) were significantly induced upon wounding in both younger and older groups, whereas matrix metallopeptidase 9 (MMP9) was induced only in the younger group. Senescence-associated β-galactosidase (SA-β-gal) was not detectable before or after wounding. This pilot study suggests the possibility that human cutaneous wound healing is characterized by differential expression of p21 and p53 between younger and older subjects.

Published
2021

7. Body Mass Index and Diabetes Incidence Across the Adult Lifespan: The Baltimore Longitudinal Study of Aging.

Author

Malandrino, Noemi, Metter, E Jeffrey, Simonsick, Eleanor M, Egan, Josephine M, Chia, Chee W, Walston, Jeremy D, Ferrucci, Luigi, and Kalyani, Rita R

Subjects
BODY mass index, GLUCOSE metabolism, DIABETES, OBESITY, OLDER people, AGING
Abstract

Context Body composition and glucose metabolism change with aging. Whether different levels of body-mass-index (BMI) are needed to define diabetes risk across the adult lifespan is unknown. Objective This work aimed to investigate whether BMI similarly reflects relative fat mass (FM) and diabetes risk across age groups. Methods Participants without diabetes from the Baltimore Longitudinal Study of Aging (973 men, 1073 women), stratified by age (<50, 50-59, 60-69, ≥70 years) and categorized by either World Health Organization (WHO)-defined BMI categories (for normal weight, overweight or obesity) or BMI quartiles. The primary exposure was BMI. The primary outcome was diabetes incidence. The relationship of BMI to dual-energy x-ray absorptiometry–derived FM was also investigated in older vs younger participants. Results The median (range) follow-up time was 7.1 years (range, 0-29.0 years). Within WHO-defined BMI categories, different age groups demonstrated significantly different FM percentage, FM/lean mass, and waist circumference (P <.05). WHO-defined BMI categories for overweight and obesity were generally related to higher diabetes risk compared to normal weight in all ages except 50 to 59 years. When BMI was categorized by quartiles, diabetes incidence increased dramatically beginning in quartile 2 (23-25 kg/m2) in older groups. BMI cutoffs with equivalent diabetes incidence rate as BMI 25 kg/m2 and 30.0 kg/m2 in individuals younger than 50 years were 22.7 kg/m2 and 25.2 kg/m2 for ages 50 to 59 years; 22.8 kg/m2 and 25.0 kg/m2 for ages 60 to 69 years; and 23.2 kg/m2 and 25.8 kg/m2 for ages 70 years and older, respectively. Conclusion WHO-defined BMI categories do not reflect similar diabetes risk across the lifespan. Diabetes incidence is greater at lower levels of BMI in older adults and may lead to underestimation of diabetes risk with aging, particularly among those traditionally classified as normal-weight individuals. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Association of Plasma Markers of Alzheimer’s Disease, Neurodegeneration, and Neuroinflammation with the Choroid Plexus Integrity in Aging.

Author

Bouhrara, Mustapha, Walker, Keenan A., Alisch, Joseph S. R., Zhaoyuan Gong, Mazucanti, Caio H., Lewis, Alexandria, Moghekar, Abhay R., Turek, Lisa, Collingham, Victoria, Shehadeh, Nader, Fantoni, Giovanna, Kaileh, Mary, Bergeron, Christopher M., Bergeron, Jan, Resnick, Susan M., and Egan, Josephine M.

Subjects
BLOOD plasma, ALZHEIMER'S disease, NEUROINFLAMMATION
Abstract

The choroid plexus (CP) is a vital brain structure essential for cerebrospinal fluid (CSF) production. Moreover, alterations in the CP’s structure and function are implicated in molecular conditions and neuropathologies including multiple sclerosis, Alzheimer’s disease, and stroke. Our goal is to provide the first characterization of the association between variation in the CP microstructure and macrostructure/volume using advanced magnetic resonance imaging (MRI) methodology, and blood-based biomarkers of Alzheimer's disease (Aß42/40 ratio; pTau181), neuroinflammation and neuronal injury (GFAP; NfL). We hypothesized that plasma biomarkers of brain pathology are associated with disordered CP structure. Moreover, since cerebral microstructural changes can precede macrostructural changes, we also conjecture that these differences would be evident in the CP microstructural integrity. Our cross-sectional study was conducted on a cohort of 108 well-characterized individuals, spanning 22-94 years of age, after excluding participants with cognitive impairments and non-exploitable MR imaging data. Established automated segmentation methods were used to identify the CP volume/macrostructure using structural MR images, while the microstructural integrity of the CP was assessed using our advanced quantitative high-resolution MR imaging of longitudinal and transverse relaxation times (T1 and T2). After adjusting for relevant covariates, positive associations were observed between pTau181, NfL and GFAP and all MRI metrics. These associations reached significance (p<0.05) except for CP volume vs. pTau181 (p=0.14), CP volume vs. NfL (p=0.35), and T2 vs. NFL (p=0.07). Further, negative associations between Aß42/40 and all MRI metrics were observed but reached significance only for Aß42/40 vs. T2 (p=0.04). These novel findings demonstrate that reduced CP macrostructural and microstructural integrity is positively associated with blood-based biomarkers of AD pathology, neurodegeneration/neuroinflammation and neurodegeneration. Degradation of the CP structure may co-occur with AD pathology and neuroinflammation ahead of clinically detectable cognitive impairment, making the CP a potential structure of interest for early disease detection or treatment monitoring. [ABSTRACT FROM AUTHOR]

Published
2024
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9. Corrigendum to “Beta cell specific cannabinoid 1 receptor deletion counteracts progression to hyperglycemia in non-obese diabetic mice” [Mol Metab 82 (2024 April) 101906]

Author

Aseer, Kanikkai Raja, primary, Mazucanti, Caio Henrique, additional, O’Connell, Jennifer F., additional, González-Mariscal, Isabel, additional, Verma, Anjali, additional, Yao, Qin, additional, Dunn, Christopher, additional, Liu, Qing-Rong, additional, Egan, Josephine M., additional, and Doyle, Máire E., additional

Published
2024
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10. Curcumin-Rich Diet Mitigates Non-Alcoholic Fatty Liver Disease (NAFLD) by Attenuating Fat Accumulation and Improving Insulin Sensitivity in Aged Female Mice under Nutritional Stress.

Author

Lamichhane, Gopal, Lee, Da-Yeon, Franks, Rienna, Olawale, Femi, Jin, Jong-Beom, Egan, Josephine M., and Kim, Yoo

Subjects
NON-alcoholic fatty liver disease, WHITE adipose tissue, WEIGHT gain, BODY composition, INSULIN sensitivity, FAT
Abstract

Simple Summary: This study aimed to understand how dietary curcumin influences metabolic abnormalities induced by a high-fat high-sugar diet (HFHSD) in aged female mice. We observed that curcumin effectively reduced body fat accumulation, steatosis of liver, and insulin resistance caused by a nutritional challenge, suggesting its potential in mitigating age-related metabolic disturbances. These findings highlight curcumin supplementation as a potential strategy to address metabolic issues associated with female aging. Background: The high incidence of metabolic syndrome in the elderly poses a significant challenge to the healthcare system, emphasizing the need for interventions tailored to geriatric patients. Given the limited focus on females in previous studies, this research aimed to evaluate the effects of dietary curcumin on obesity and NAFLD outcomes in naturally aged (18-month-old) female mice. Methods: Female C57BL/6 mice aged 18 months were fed a normal chow diet (NCD) and a HFHSD, with or without curcumin (0.4% w/w), for an 8-week period. Parameters included food intake, body weight, insulin tolerance test (ITT), glucose tolerance test (GTT), percentage fat mass, hepatic triglyceride, and cholesterol levels, and a histological examination for NAFLD detection, qPCR, and immunoblotting analyses were performed. Results: The cumulative body weight gain after 8 weeks in the aged female mice supplemented with curcumin and fed an HFHSD was significantly lower (10.84 ± 1.09 g) compared to those fed a HFHSD alone (15.28 ± 1.26 g). Curcumin supplementation also resulted in reduced total body fat (HFHSD group 50.83 ± 1.71% vs. HFHSD+CUR 41.46 ± 3.21%), decreased epidydimal fat mass (HFHSD: 3.79 ± 0.29 g vs. HFHSD+CUR: 2.66 ± 0.30 g), and repaired adipogenic signaling in the white adipose tissue. Furthermore, curcumin lowered triglyceride and cholesterol deposition in the liver, preventing hepatic steatosis and improving hepatic insulin sensitivity. Conclusions: Curcumin demonstrates the ability to ameliorate the deleterious effects of HFHSD in aged female mice by reducing body fat composition, modulating adipogenic signaling in the white adipose tissue, and improving insulin homeostasis and non-alcoholic fatty deposition in the liver. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Disulfiram Treatment Normalizes Body Weight in Obese Mice

Author

Bernier, Michel, Mitchell, Sarah J., Wahl, Devin, Diaz, Antonio, Singh, Abhishek, Seo, Wonhyo, Wang, Mingy, Ali, Ahmed, Kaiser, Tamzin, Price, Nathan L., Aon, Miguel A., Kim, Eun-Young, Petr, Michael A., Cai, Huan, Warren, Alessa, Di Germanio, Clara, Di Francesco, Andrea, Fishbein, Ken, Guiterrez, Vince, Harney, Dylan, Koay, Yen Chin, Mach, John, Enamorado, Ignacio Navas, Pulpitel, Tamara, Wang, Yushi, Zhang, Jing, Zhang, Li, Spencer, Richard G., Becker, Kevin G., Egan, Josephine M., Lakatta, Edward G., O’Sullivan, John, Larance, Mark, LeCouteur, David G., Cogger, Victoria C., Gao, Bin, Fernandez-Hernando, Carlos, Cuervo, Ana Maria, and de Cabo, Rafael

Published
2020
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13. Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Author

Lagou, Vasiliki, Mägi, Reedik, Hottenga, Jouke- Jan, Grallert, Harald, Perry, John R. B., Bouatia-Naji, Nabila, Marullo, Letizia, Rybin, Denis, Jansen, Rick, Min, Josine L., Dimas, Antigone S., Ulrich, Anna, Zudina, Liudmila, Gådin, Jesper R., Jiang, Longda, Faggian, Alessia, Bonnefond, Amélie, Fadista, Joao, Stathopoulou, Maria G., Isaacs, Aaron, Willems, Sara M., Navarro, Pau, Tanaka, Toshiko, Jackson, Anne U., Montasser, May E., O’Connell, Jeff R., Bielak, Lawrence F., Webster, Rebecca J., Saxena, Richa, Stafford, Jeanette M., Pourcain, Beate St, Timpson, Nicholas J., Salo, Perttu, Shin, So-Youn, Amin, Najaf, Smith, Albert V., Li, Guo, Verweij, Niek, Goel, Anuj, Ford, Ian, Johnson, Paul C. D., Johnson, Toby, Kapur, Karen, Thorleifsson, Gudmar, Strawbridge, Rona J., Rasmussen-Torvik, Laura J., Esko, Tõnu, Mihailov, Evelin, Fall, Tove, Fraser, Ross M., Mahajan, Anubha, Kanoni, Stavroula, Giedraitis, Vilmantas, Kleber, Marcus E., Silbernagel, Günther, Meyer, Julia, Müller-Nurasyid, Martina, Ganna, Andrea, Sarin, Antti-Pekka, Yengo, Loic, Shungin, Dmitry, Luan, Jian’an, Horikoshi, Momoko, An, Ping, Sanna, Serena, Boettcher, Yvonne, Rayner, N. William, Nolte, Ilja M., Zemunik, Tatijana, Iperen, Erik van, Kovacs, Peter, Hastie, Nicholas D., Wild, Sarah H., McLachlan, Stela, Campbell, Susan, Polasek, Ozren, Carlson, Olga, Egan, Josephine, Kiess, Wieland, Willemsen, Gonneke, Kuusisto, Johanna, Laakso, Markku, Dimitriou, Maria, Hicks, Andrew A., Rauramaa, Rainer, Bandinelli, Stefania, Thorand, Barbara, Liu, Yongmei, Miljkovic, Iva, Lind, Lars, Doney, Alex, Perola, Markus, Hingorani, Aroon, Kivimaki, Mika, Kumari, Meena, Bennett, Amanda J., Groves, Christopher J., Herder, Christian, Koistinen, Heikki A., Kinnunen, Leena, Faire, Ulf de, Bakker, Stephan J. L., Uusitupa, Matti, Palmer, Colin N. A., Jukema, J. Wouter, Sattar, Naveed, Pouta, Anneli, Snieder, Harold, Boerwinkle, Eric, Pankow, James S., Magnusson, Patrik K., Krus, Ulrika, Scapoli, Chiara, de Geus, Eco J. C. N., Blüher, Matthias, Wolffenbuttel, Bruce H. R., Province, Michael A., Abecasis, Goncalo R., Meigs, James B., Hovingh, G. Kees, Lindström, Jaana, Wilson, James F., Wright, Alan F., Dedoussis, George V., Bornstein, Stefan R., Schwarz, Peter E. H., Tönjes, Anke, Winkelmann, Bernhard R., Boehm, Bernhard O., März, Winfried, Metspalu, Andres, Price, Jackie F., Deloukas, Panos, Körner, Antje, Lakka, Timo A., Keinanen-Kiukaanniemi, Sirkka M., Saaristo, Timo E., Bergman, Richard N., Tuomilehto, Jaakko, Wareham, Nicholas J., Langenberg, Claudia, Männistö, Satu, Franks, Paul W., Hayward, Caroline, Vitart, Veronique, Kaprio, Jaakko, Visvikis-Siest, Sophie, Balkau, Beverley, Altshuler, David, Rudan, Igor, Stumvoll, Michael, Campbell, Harry, van Duijn, Cornelia M., Gieger, Christian, Illig, Thomas, Ferrucci, Luigi, Pedersen, Nancy L., Pramstaller, Peter P., Boehnke, Michael, Frayling, Timothy M., Shuldiner, Alan R., Peyser, Patricia A., Kardia, Sharon L. R., Palmer, Lyle J., Penninx, Brenda W., Meneton, Pierre, Harris, Tamara B., Navis, Gerjan, Harst, Pim van der, Smith, George Davey, Forouhi, Nita G., Loos, Ruth J. F., Salomaa, Veikko, Soranzo, Nicole, Boomsma, Dorret I., Groop, Leif, Tuomi, Tiinamaija, Hofman, Albert, Munroe, Patricia B., Gudnason, Vilmundur, Siscovick, David S., Watkins, Hugh, Lecoeur, Cecile, Vollenweider, Peter, Franco-Cereceda, Anders, Eriksson, Per, Jarvelin, Marjo-Riitta, Stefansson, Kari, Hamsten, Anders, Nicholson, George, Karpe, Fredrik, Dermitzakis, Emmanouil T., Lindgren, Cecilia M., McCarthy, Mark I., Froguel, Philippe, Kaakinen, Marika A., Lyssenko, Valeriya, Watanabe, Richard M., Ingelsson, Erik, Florez, Jose C., Dupuis, Josée, Barroso, Inês, Morris, Andrew P., and Prokopenko, Inga

Published
2021
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15. No Interactions Between Previously Associated 2-Hour Glucose Gene Variants and Physical Activity or BMI on 2-Hour Glucose Levels

Author

Scott, Robert A, Chu, Audrey Y, Grarup, Niels, Manning, Alisa K, Hivert, Marie-France, Shungin, Dmitry, Tönjes, Anke, Yesupriya, Ajay, Barnes, Daniel, Bouatia-Naji, Nabila, Glazer, Nicole L, Jackson, Anne U, Kutalik, Zoltán, Lagou, Vasiliki, Marek, Diana, Rasmussen-Torvik, Laura J, Stringham, Heather M, Tanaka, Toshiko, Aadahl, Mette, Arking, Dan E, Bergmann, Sven, Boerwinkle, Eric, Bonnycastle, Lori L, Bornstein, Stefan R, Brunner, Eric, Bumpstead, Suzannah J, Brage, Soren, Carlson, Olga D, Chen, Han, Chen, Yii-Der Ida, Chines, Peter S, Collins, Francis S, Couper, David J, Dennison, Elaine M, Dowling, Nicole F, Egan, Josephine S, Ekelund, Ulf, Erdos, Michael R, Forouhi, Nita G, Fox, Caroline S, Goodarzi, Mark O, Grässler, Jürgen, Gustafsson, Stefan, Hallmans, Göran, Hansen, Torben, Hingorani, Aroon, Holloway, John W, Hu, Frank B, Isomaa, Bo, Jameson, Karen A, Johansson, Ingegerd, Jonsson, Anna, Jørgensen, Torben, Kivimaki, Mika, Kovacs, Peter, Kumari, Meena, Kuusisto, Johanna, Laakso, Markku, Lecoeur, Cécile, Lévy-Marchal, Claire, Li, Guo, Loos, Ruth JF, Lyssenko, Valeri, Marmot, Michael, Marques-Vidal, Pedro, Morken, Mario A, Müller, Gabriele, North, Kari E, Pankow, James S, Payne, Felicity, Prokopenko, Inga, Psaty, Bruce M, Renström, Frida, Rice, Ken, Rotter, Jerome I, Rybin, Denis, Sandholt, Camilla H, Sayer, Avan A, Shrader, Peter, Schwarz, Peter EH, Siscovick, David S, Stančáková, Alena, Stumvoll, Michael, Teslovich, Tanya M, Waeber, Gérard, Williams, Gordon H, Witte, Daniel R, Wood, Andrew R, Xie, Weijia, Boehnke, Michael, Cooper, Cyrus, Ferrucci, Luigi, Froguel, Philippe, Groop, Leif, Kao, WH Linda, Vollenweider, Peter, Walker, Mark, Watanabe, Richard M, Pedersen, Oluf, and Meigs, James B

Subjects
Biomedical and Clinical Sciences, Clinical Research, Genetics, Diabetes, Prevention, Obesity, Nutrition, 2.1 Biological and endogenous factors, Aetiology, 2.3 Psychological, social and economic factors, Metabolic and endocrine, Blood Glucose, Body Mass Index, Epigenesis, Genetic, Gene Expression Regulation, Genotype, Humans, Life Style, Motor Activity, Polymorphism, Single Nucleotide, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

Published
2012

16. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Author

Dastani, Zari, Hivert, Marie-France, Timpson, Nicholas, Perry, John RB, Yuan, Xin, Scott, Robert A, Henneman, Peter, Heid, Iris M, Kizer, Jorge R, Lyytikäinen, Leo-Pekka, Fuchsberger, Christian, Tanaka, Toshiko, Morris, Andrew P, Small, Kerrin, Isaacs, Aaron, Beekman, Marian, Coassin, Stefan, Lohman, Kurt, Qi, Lu, Kanoni, Stavroula, Pankow, James S, Uh, Hae-Won, Wu, Ying, Bidulescu, Aurelian, Rasmussen-Torvik, Laura J, Greenwood, Celia MT, Ladouceur, Martin, Grimsby, Jonna, Manning, Alisa K, Liu, Ching-Ti, Kooner, Jaspal, Mooser, Vincent E, Vollenweider, Peter, Kapur, Karen A, Chambers, John, Wareham, Nicholas J, Langenberg, Claudia, Frants, Rune, Willems-Vandijk, Ko, Oostra, Ben A, Willems, Sara M, Lamina, Claudia, Winkler, Thomas W, Psaty, Bruce M, Tracy, Russell P, Brody, Jennifer, Chen, Ida, Viikari, Jorma, Kähönen, Mika, Pramstaller, Peter P, Evans, David M, St Pourcain, Beate, Sattar, Naveed, Wood, Andrew R, Bandinelli, Stefania, Carlson, Olga D, Egan, Josephine M, Böhringer, Stefan, van Heemst, Diana, Kedenko, Lyudmyla, Kristiansson, Kati, Nuotio, Marja-Liisa, Loo, Britt-Marie, Harris, Tamara, Garcia, Melissa, Kanaya, Alka, Haun, Margot, Klopp, Norman, Wichmann, H-Erich, Deloukas, Panos, Katsareli, Efi, Couper, David J, Duncan, Bruce B, Kloppenburg, Margreet, Adair, Linda S, Borja, Judith B, DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, Wilson, James G, Musani, Solomon, Guo, Xiuqing, Johnson, Toby, Semple, Robert, Teslovich, Tanya M, Allison, Matthew A, Redline, Susan, Buxbaum, Sarah G, Mohlke, Karen L, Meulenbelt, Ingrid, Ballantyne, Christie M, Dedoussis, George V, Hu, Frank B, Liu, Yongmei, Paulweber, Bernhard, Spector, Timothy D, Slagboom, P Eline, Ferrucci, Luigi, and Jula, Antti

Subjects
DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, DIAGRAM Consortium, GIANT Consortium, Global B Pgen Consortium, Procardis Consortium, MAGIC investigators, GLGC Consortium, Humans, Diabetes Mellitus, Type 2, Insulin Resistance, Genetic Predisposition to Disease, Glucose Tolerance Test, Waist-Hip Ratio, Gene Expression, Polymorphism, Single Nucleotide, African Americans, Asian Continental Ancestry Group, European Continental Ancestry Group, Female, Male, Adiponectin, Cholesterol, HDL, Metabolic Networks and Pathways, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, Cholesterol, HDL, Genetics, Developmental Biology
Abstract

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p

Published
2012

21. Cross‐sectional analysis of healthy individuals across decades: Aging signatures across multiple physiological compartments.

Author

Moaddel, Ruin, Ubaida‐Mohien, Ceereena, Tanaka, Toshiko, Tian, Qu, Candia, Julián, Moore, Ann Zenobia, Lovett, Jacqueline, Fantoni, Giovanna, Shehadeh, Nader, Turek, Lisa, Collingham, Victoria, Kaileh, Mary, Chia, Chee W., Sen, Ranjan, Egan, Josephine M., and Ferrucci, Luigi

Subjects
CELLULAR aging, CROSS-sectional method, KIDNEY physiology, SKELETAL muscle, LYSOSOMES, METABOLISM, MICROBIAL metabolism
Abstract

The study of age‐related biomarkers from different biofluids and tissues within the same individual might provide a more comprehensive understanding of age‐related changes within and between compartments as these changes are likely highly interconnected. Understanding age‐related differences by compartments may shed light on the mechanism of their reciprocal interactions, which may contribute to the phenotypic manifestations of aging. To study such possible interactions, we carried out a targeted metabolomic analysis of plasma, skeletal muscle, and urine collected from healthy participants, age 22–92 years, and identified 92, 34, and 35 age‐associated metabolites, respectively. The metabolic pathways that were identified across compartments included inflammation and cellular senescence, microbial metabolism, mitochondrial health, sphingolipid metabolism, lysosomal membrane permeabilization, vascular aging, and kidney function. [ABSTRACT FROM AUTHOR]

Published
2024
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22. Absence of cannabinoid 1 receptor in beta cells protects against high-fat/high-sugar diet-induced beta cell dysfunction and inflammation in murine islets

Author

González-Mariscal, Isabel, Montoro, Rodrigo A., Doyle, Máire E., Liu, Qing-Rong, Rouse, Michael, O’Connell, Jennifer F., Santa-Cruz Calvo, Sara, Krzysik-Walker, Susan M., Ghosh, Soumita, Carlson, Olga D., Lehrmann, Elin, Zhang, Yongqing, Becker, Kevin G., Chia, Chee W., Ghosh, Paritosh, and Egan, Josephine M.

Published
2018
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24. A hyper-quiescent chromatin state formed during aging is reversed by regeneration

Author

Yang, Na, primary, Occean, James R., additional, Melters, Daniël P., additional, Shi, Changyou, additional, Wang, Lin, additional, Stransky, Stephanie, additional, Doyle, Maire E., additional, Cui, Chang-Yi, additional, Delannoy, Michael, additional, Fan, Jinshui, additional, Slama, Eliza, additional, Egan, Josephine M., additional, De, Supriyo, additional, Cunningham, Steven C., additional, de Cabo, Rafael, additional, Sidoli, Simone, additional, Dalal, Yamini, additional, and Sen, Payel, additional

Published
2023
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25. Effects of Sex, Strain, and Energy Intake on Hallmarks of Aging in Mice

Author

Mitchell, Sarah J., Madrigal-Matute, Julio, Scheibye-Knudsen, Morten, Fang, Evandro, Aon, Miguel, González-Reyes, José A., Cortassa, Sonia, Kaushik, Susmita, Gonzalez-Freire, Marta, Patel, Bindi, Wahl, Devin, Ali, Ahmed, Calvo-Rubio, Miguel, Burón, María I., Guiterrez, Vincent, Ward, Theresa M., Palacios, Hector H., Cai, Huan, Frederick, David W., Hine, Christopher, Broeskamp, Filomena, Habering, Lukas, Dawson, John, Beasley, T. Mark, Wan, Junxiang, Ikeno, Yuji, Hubbard, Gene, Becker, Kevin G., Zhang, Yongqing, Bohr, Vilhelm A., Longo, Dan L., Navas, Placido, Ferrucci, Luigi, Sinclair, David A., Cohen, Pinchas, Egan, Josephine M., Mitchell, James R., Baur, Joseph A., Allison, David B., Anson, R. Michael, Villalba, José M., Madeo, Frank, Cuervo, Ana Maria, Pearson, Kevin J., Ingram, Donald K., Bernier, Michel, and de Cabo, Rafael

Published
2016
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32. Empagliflozin Induced Ketosis, Upregulated IGF-1/Insulin Receptors and the Canonical Insulin Signaling Pathway in Neurons, and Decreased the Excitatory Neurotransmitter Glutamate in the Brain of Non-Diabetics

Author

Avgerinos, Konstantinos I., primary, Mullins, Roger J., additional, Vreones, Michael, additional, Mustapic, Maja, additional, Chen, Qinghua, additional, Melvin, Denise, additional, Kapogiannis, Dimitrios, additional, and Egan, Josephine M., additional

Published
2022
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40. Resveratrol Improves Adipose Insulin Signaling and Reduces the Inflammatory Response in Adipose Tissue of Rhesus Monkeys on High-Fat, High-Sugar Diet

Author

Jimenez-Gomez, Yolanda, Mattison, Julie A., Pearson, Kevin J., Martin-Montalvo, Alejandro, Palacios, Hector H., Sossong, Alex M., Ward, Theresa M., Younts, Caitlin M., Lewis, Kaitlyn, Allard, Joanne S., Longo, Dan L., Belman, Jonathan P., Malagon, Maria M., Navas, Placido, Sanghvi, Mitesh, Moaddel, Ruin, Tilmont, Edward M., Herbert, Richard L., Morrell, Christopher H., Egan, Josephine M., Baur, Joseph A., Ferrucci, Luigi, Bogan, Jonathan S., Bernier, Michel, and de Cabo, Rafael

Published
2013
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41. PHYSIOLOGY OF THE TONGUE WITH EMPHASIS ON TASTE TRANSDUCTION.

Author

Doyle, Máire E., Premathilake, Hasitha U., Qin Yao, Mazucanti, Caio H., and Egan, Josephine M.

Subjects
TASTE perception, SENSE organs, TASTE buds, PHYSIOLOGY, TONGUE
Abstract

The tongue is a complex multifunctional organ that interacts and senses both interoceptively and exteroceptively. Although it is easily visible to almost all of us, it is relatively understudied and what is in the literature is often contradictory or is not comprehensively reported. The tongue is both a motor and a sensory organ: motor in that it is required for speech and mastication, and sensory in that it receives information to be relayed to the central nervous system pertaining to the safety and quality of the contents of the oral cavity. Additionally, the tongue and its taste apparatus form part of an innate immune surveillance system. For example, loss or alteration in taste perception can be an early indication of infection as became evident during the present global SARS-CoV-2 pandemic. Here, we particularly emphasize the latest updates in the mechanisms of taste perception, taste bud formation and adult taste bud renewal, and the presence and effects of hormones on taste perception, review the understudied lingual immune system with specific reference to SARS-CoV-2, discuss nascent work on tongue microbiome, as well as address the effect of systemic disease on tongue structure and function, especially in relation to taste. [ABSTRACT FROM AUTHOR]

Published
2023
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50. Fasting blood glucose as a predictor of mortality: Lost in translation

Author

Palliyaguru, Dushani L., Shiroma, Eric J., Nam, John K., Duregon, Eleonora, Vieira Ligo Teixeira, Camila, Price, Nathan L., Bernier, Michel, Camandola, Simonetta, Vaughan, Kelli L., Colman, Ricki J., Deighan, Andrew, Korstanje, Ron, Peters, Luanne L., Dickinson, Stephanie L., Ejima, Keisuke, Simonsick, Eleanor M., Launer, Lenore J., Chia, Chee W., Egan, Josephine, Allison, David B., Churchill, Gary A., Anderson, Rozalyn M., Ferrucci, Luigi, Mattison, Julie A., and de Cabo, Rafael

Published
2021
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