Article
Geriatrics & Gerontology
Yimin Fang, David Medina, Robert Stockwell, Samuel McFadden, Erin R. Hascup, Kevin N. Hascup, Andrzej Bartke
Summary: GHR-KO mice have enhanced resistance to cold stress, but male GHR-KO mice have shortened lifespan in cold environment compared to females. Female GHR-KO and wild-type mice show higher resistance to cold stress than males.
Article
Cell Biology
S. Joseph Endicott, Alexander C. Monovich, Eric L. Huang, Evelynn Henry, Dennis N. Boynton, Logan J. Beckmann, Michael J. MacCoss, Richard A. Miller
Summary: Mice deficient in growth hormone receptor exhibit a dramatic lifespan extension and elevated hepatic chaperone-mediated autophagy. The increased CMA in these mice downregulates proteins involved in ribosomal structure, translation, and acetyl-CoA production, which in turn affects lipid droplet accumulation.
Article
Endocrinology & Metabolism
Irina C. Frei, Diana Weissenberger, Michael N. Hall, Mitsugu Shimobayashi
Summary: Mammalian target of rapamycin complex 2 (mTORC2) is a protein kinase complex that plays an important role in energy homeostasis. Loss of adipose mTORC2 reduces lipogenic enzyme expression and de novo lipogenesis in adipose tissue. Adipose-specific mTORC2 knockout mice also display triglyceride accumulation in the liver.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2023)
Article
Multidisciplinary Sciences
James Okoh, Jacqunae Mays, Alexandre Bacq, Juan A. Oses-Prieto, Stefka Tyanova, Chien-Ju Chen, Khalel Imanbeyev, Marion Doladilhe, Hongyi Zhou, Paymaan Jafar-Nejad, Alma Burlingame, Jeffrey Noebels, Stephanie Baulac, Mauro Costa-Mattioli
Summary: Inhibition of mTORC2 suppresses seizures in animal models with multiple etiologies, thereby enhancing neuronal resilience to the pathological hypersynchrony associated with epilepsy.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Christoph C. Carter, Fred D. Mast, Jean Paul Olivier, Natasha M. Bourgeois, Alexis Kaushansky, John D. Aitchison
Summary: This study reveals the important role of mTORC2 in dengue replication. It is not only activated during viral replication, but also promotes the survival of infected cells by inhibiting apoptosis, maximizing viral replication.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Tatsuya Shioda, Ittetsu Takahashi, Kensuke Ikenaka, Naonobu Fujita, Tomotake Kanki, Toshihiko Oka, Hideki Mochizuki, Adam Antebi, Tamotsu Yoshimori, Shuhei Nakamura
Summary: Accumulating evidence suggests that the molecular network involving neuronal MML-1 function is crucial for regulating systemic aging. This study demonstrates that MML-1 and its heterodimer partners play a primary role in neurons to extend longevity in germlineless animals, acting via downstream cascades that are distinct from HLH-30. The MML-1-GLT-5 axis in neurons is critical for maintaining proteostasis and reducing oxidative stress in long-lived animals through autophagy and peroxidase MLT-7, respectively.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Immunology
Yongning Lu, Miao Liu, Nicholas J. Tursi, Bin Yan, Xiang Cao, Qi Che, Nianqin Yang, Xi Dong
Summary: The destruction of the blood-testis barrier (BTB) following uropathogenic E. coli (UPEC) infection may be a critical component of orchitis pathogenesis. Abnormal activation of the mTOR signaling pathway is associated with BTB impairment during UPEC-induced orchitis. Rapamycin can protect the BTB and does not aggravate spermatogenic degeneration in infected rats.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Sheikh Tahir Majeed, Rabiya Majeed, Aijaz A. Malik, Khurshid Iqbal Andrabi
Summary: S6K1 is regulated by mTORC1 and is involved in cell growth and proliferation. We have identified eIF4E as an intermediate in transmitting signals from mTORC1 to S6K1 and found that mTORC1 induces eIF4E phosphorylation and interaction with S6K1. We further discovered that mTORC2 acts as a physiological kinase for S6K1's hydrophobic motif phosphorylation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2023)
Article
Cell Biology
Kaixuan Guo, Cheng Liu, Juanyi Shi, Cong Lai, Ze Gao, Jiawen Luo, Zhuohang Li, Zhuang Tang, Kuiqing Li, Kewei Xu
Summary: Dysregulated HMMR is associated with poor prognosis in prostate cancer. HMMR promotes PCa proliferation and metastasis through interacting with AURKA and activating the mTORC2/AKT pathway. Moreover, sustained activation of mTORC2/AKT pathway upregulates E2F1, which further promotes HMMR transcription, forming a positive feedback loop that contributes to PCa progression. Administration of mTOR inhibitor partially antagonizes HMMR-mediated PCa progression.
CELL DEATH DISCOVERY
(2023)
Article
Cell Biology
Yumiko Ono, Kenji Matsuzawa, Junichi Ikenouchi
Summary: This study reveals that epithelial cells selectively expand the apical membrane and maintain plasma membrane tension in hypo-osmotic stress through the activation of mTORC2-Rab35 axis, which enhances the transport of secretory vesicles containing major lipid to the apical membrane.
JOURNAL OF CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Xiupeng Chen, Jie Li, Zhongbao Gao, Yang Yang, Wenqing Kuang, Yue Dong, Gek Huey Chua, Xiahe Huang, Binhua Jiang, He Tian, Yingchun Wang, Xun Huang, Yan Li, Sin Man Lam, Guanghou Shui
Summary: By studying the CPE synthase in Drosophila, we found that membrane CPE plays a crucial role in maintaining circadian behavior and lifespan. Deficiency in CPE leads to arrhythmic locomotor behavior and shortened lifespan, while increasing CPE has the opposite effect. Furthermore, dysregulated synaptic glutamate utilization and transport were found to be associated with CPE deficiency.
NATIONAL SCIENCE REVIEW
(2022)
Article
Biochemistry & Molecular Biology
Aaron Seth Tooley, Dubek Kazyken, Cagri Bodur, Ian E. Gonzalez, Diane C. Fingar
Summary: TBK1 can directly activate mTOR complex 2 (mTORC2) to promote Akt phosphorylation, involving in cellular metabolism and proliferation. Interaction between TBK1 and mTOR serves as key nodes in two major signaling networks.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Hematology
Zihan Tang, Hui Shi, Changming Chen, Jialin Teng, Jing Dai, Xinxing Ouyang, Honglei Liu, Qiongyi Hu, Xiaobing Cheng, Junna Ye, Yutong Su, Yue Sun, Haoyu Pan, Xuefeng Wang, Junling Liu, Bing Su, Chengde Yang, Yanyan Xu, Tingting Liu
Summary: This study elucidated a novel mechanism involving the mTORC2/Akt pathway, which mediates the promotion of platelet activation and induction of thrombosis by the anti-beta 2GP1 antibody. The findings suggest that SIN1 may be a promising therapeutic target for the treatment of APS.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Julia C. Stokes, Rebecca L. Bornstein, Katerina James, Kyung Yeon Park, Kira A. Spencer, Katie Vo, John C. Snell, Brittany M. Johnson, Philip G. Morgan, Margaret M. Sedensky, Nathan A. Baertsch, Simon C. Johnson
Summary: Leukocyte proliferation plays a crucial role in the pathogenesis of Leigh syndrome, and inhibiting leukocytes can improve disease symptoms and prolong patient survival. This study has important implications for understanding mitochondrial disease mechanisms and developing new therapeutic strategies.
Review
Biology
Eisuke Tasaki, Mamoru Takata, Kenji Matsuura
Summary: Lifespan varies greatly across different organisms, with some extending longevity through trade-offs between reproduction and longevity, while social insect reproductives are exceptions, exhibiting both high reproductive outputs and long lives, attracting much attention for the reasons and mechanisms behind their extended lifespans.
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
(2021)
Article
Nutrition & Dietetics
William O. Jonsson, Nicholas S. Margolies, Emily T. Mirek, Qian Zhang, Melissa A. Linden, Cristal M. Hill, Christopher Link, Nazmin Bithi, Brian Zalma, Jordan L. Levy, Ashley P. Pettit, Joshua W. Miller, Christopher Hine, Christopher D. Morrison, Thomas W. Gettys, Benjamin F. Miller, Karyn L. Hamilton, Ronald C. Wek, Tracy G. Anthony
Summary: The study investigated the role of ATF4 as a converging point in the integrated stress response during dietary sulfur amino acid restriction (SAAR). The results showed that ATF4 is essential for the sustained production of endogenous hydrogen sulfide and also plays a role in inducing hepatokine fibroblast growth factor 21. Additionally, biological sex was found to be a determinant of the response to dietary SAAR independent of ATF4 status.
JOURNAL OF NUTRITION
(2021)
Article
Geriatrics & Gerontology
Tatiana D. Saccon, Monique T. Rovani, Driele N. Garcia, Jorgea Pradiee, Rafael G. Mondadori, Luis Augusto X. Cruz, Carlos C. Barros, Yimin Fang, Samuel McFadden, Jeffrey B. Mason, Andrzej Bartke, Michal M. Masternak, Augusto Schneider
Summary: The study indicates that growth hormone plays an important role in ovarian reserve in mice, with GH-deficient mice showing reduced DNA double-strand breaks and GH treatment leading to an increase in DNA breaks. Conversely, transgenic mice with excessive GH exhibit significantly increased macrophage infiltration in ovarian tissue.
Article
Geriatrics & Gerontology
Alessandro Bitto, Mitchell B. Lee, Cristal M. Hill, Ron Korstanje, Matt Kaeberlein
Summary: The AGE Presents Introduction to Geroscience video lecture series provides high-quality didactic videos and teaching materials focusing on foundational topics in aging biology, aiming to enhance public understanding of geroscience and provide educators with classroom tools.
Article
Neurosciences
Marina A. DuVall, Carolyn E. Coulter, Jasmin L. Gosey, Matthew J. Herrera, Cristal M. Hill, Rajvi R. Jariwala, Lauren E. Maisano, Laura A. Moldovan, Christopher D. Morrison, Ngozi V. Nwabueze, Hunter X. Sikaffy, David H. McDougal
Summary: The study found that under conditions of reduced leptin levels, there were defects in neuroendocrine responses to hypoglycemia, which were reversed by leptin treatment, potentially preventing the development of hypoglycemia-associated autonomic failure (HAAF) in individuals with diabetes.
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
(2021)
Review
Biochemistry & Molecular Biology
Rachel J. Waldemer-Streyer, Dongwook Kim, Jie Chen
Summary: Regeneration of adult skeletal muscle in mammals is a complex process regulated by multiple proteins and signaling pathways. Cytokines play a crucial role in skeletal myogenesis, with both infiltrating immune cells and the muscle itself secreting these signaling molecules. This review focuses on muscle-secreted cytokines that have been shown to be involved in myogenic differentiation and muscle regeneration.
Article
Endocrinology & Metabolism
Christopher D. Morrison, Marina A. DuVall, Cristal M. Hill, Redin A. Spann, David H. McDougal
Summary: Hypoglycemia poses a significant challenge in the clinical management of diabetes. Recent evidence suggests a role for leptin in regulating hypoglycemic counterregulation, with potential clinical utility in preventing hypoglycemia.
JOURNAL OF DIABETES AND ITS COMPLICATIONS
(2021)
Article
Geriatrics & Gerontology
Augusto Schneider, Berta Victoria, Maria Isabel Schiavon Cousen, Yimin Fang, Samuel McFadden, Justin Darcy, Adam Gesing, Erin R. Hascup, Kevin N. Hascup, Andrzej Bartke, Michal M. Masternak
Summary: The expression profile of different adipose tissue depots in GHRKO mice is affected by environmental temperature, with brown adipose tissue (BAT) being the most responsive. BAT Ucp1 and Ucp3 expression decreases under thermoneutral conditions in both normal (N) and GHRKO mice. In contrast, subcutaneous white adipose tissue (sWAT) shows the most divergent response to thermoneutrality in GHRKO mice compared to N mice.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2022)
Review
Multidisciplinary Sciences
Mitchell B. Lee, Cristal M. Hill, Alessandro Bitto, Matt Kaeberlein
Summary: Caloric restriction and other anti-aging diets can extend lifespan and delay age-related pathology. These diets offer new insights into the mechanisms of biological aging and potential clinical applications.
Editorial Material
Geriatrics & Gerontology
Michaela E. Murphy, Akilavalli Narasimhan, Alexis Adrian, Ankur Kumar, Cara L. Green, Carolina Soto-Palma, Chathurika Henpita, Christina Camell, Christopher S. Morrow, Chung-Yang Yeh, Claire E. Richardson, Cristal M. Hill, Darcie L. Moore, Dudley W. Lamming, Eric R. McGregor, Heather A. Simmons, Heidi H. Pak, Hua Bai, John M. Denu, Josef Clark, Judith Simcox, Kishore Chittimalli, Korbyn Dahlquist, Kyoo-a Lee, Mariah Calubag, Mark Bouska, Matthew J. Yousefzadeh, Michelle Sonsalla, Reji Babygirija, Rong Yuan, Tadataka Tsuji, Timothy Rhoads, Vinal Menon, Yagna PR. Jarajapu, Yun Zhu
Article
Geriatrics & Gerontology
Samuel McFadden, Lindsey N. Sime, MaKayla F. Cox, Caleigh A. Findley, Mackenzie R. Peck, Kathleen Quinn, Yimin Fang, Andrzej Bartke, Erin R. Hascup, Kevin N. Hascup
Summary: Metabolic dysfunction increases with age and is a contributing factor to Alzheimer's disease (AD) development. In a study on AD mice, it was found that insulin sensitivity and glucose homeostasis were impaired, but could be partially improved by exposure to mild hypothermic environmental temperature. However, glucose tolerance remained impaired and there were additional sexually dimorphic mechanisms that may contribute to the glucose dysregulation in AD mice.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Article
Geriatrics & Gerontology
Yimin Fang, David Medina, Robert Stockwell, Samuel McFadden, Erin R. Hascup, Kevin N. Hascup, Andrzej Bartke
Summary: GHR-KO mice have enhanced resistance to cold stress, but male GHR-KO mice have shortened lifespan in cold environment compared to females. Female GHR-KO and wild-type mice show higher resistance to cold stress than males.
Editorial Material
Cell Biology
Jie Chen
NATURE CELL BIOLOGY
(2023)
Article
Geriatrics & Gerontology
Jae-Sung You, Yongdeok Kim, Soohyun Lee, Rashid Bashir, Jie Chen
Summary: The RhoA/ROCK signaling pathway plays a critical role in the pathology of Duchenne muscular dystrophy (DMD), and inhibiting ROCK can improve muscle strength and quality in DMD by rescuing autophagy.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Geriatrics & Gerontology
Yimin Fang, David Medina, Robert Stockwell, Sam McFadden, Kathleen Quinn, Mackenzie R. Peck, Andrzej Bartke, Kevin N. Hascup, Erin R. Hascup
Summary: Senolytic treatment in aged mice clears senescent cell burden leading to functional improvements, but less is known about the effects when administered prior to significant senescent cell accumulation.
Article
Physiology
Han Fang, Sujoy Ghosh, Landon C. Sims, Kirsten P. Stone, Cristal M. Hill, Denisha Spires, Daria Ilatovskaya, Christopher D. Morrison, Thomas W. Gettys, Krisztian Stadler
Summary: Long-term protein restriction is not beneficial for an aging kidney, as it can lead to renal injury and inflammation. The presence of FGF21 is essential for countering the negative effects of a low-protein diet on the kidney during aging.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2021)