Article
Geriatrics & Gerontology
Christian J. Elliehausen, Dennis M. Minton, Alexander D. Nichol, Adam R. Konopka
Summary: The study examined the effects of dietary rapamycin with or without metformin on skeletal muscle mitochondrial function in guinea pigs with age-related osteoarthritis. The results showed that both rapamycin and rapamycin with metformin decreased complex I-linked respiration and increased ADP sensitivity, suggesting potential implications for skeletal muscle function in osteoarthritis.
EXPERIMENTAL GERONTOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Nikolaus Bresgen, Melanie Kovacs, Angelika Lahnsteiner, Thomas Klaus Felder, Mark Rinnerthaler
Summary: Many hallmarks, including mitochondrial dysfunction, epigenetic alterations, and loss of proteostasis, exist that describe the cellular aging process. In addition, lipid droplets, a well-described cell organelle in the metabolic context, accumulate with increasing age, adding to the aging-associated process. Lipid droplets not only serve as fat stores, but also control cell integrity by mitigating lipotoxic and proteotoxic insults. Longevity interventions, such as mTOR inhibition, lead to strong accumulation of lipid droplets in various organisms. In mammals, lipid droplets play a complex role during the aging process, as they can both mitigate toxicity and cause problems for cells and tissues in different disease states.
Article
Cell Biology
Barbara Infante, Francesco Bellanti, Michele Correale, Paola Pontrelli, Rossana Franzin, Serena Leo, Martina Calvaruso, Silvia Mercuri, Giuseppe Stefano Netti, Elena Ranieri, Natale Daniele Brunetti, Giuseppe Grandaliano, Loreto Gesualdo, Gaetano Serviddio, Giuseppe Castellano, Giovanni Stallone
Summary: This study demonstrated that the use of mTOR inhibitors in immunosuppressive protocols can prevent the occurrence and signs of cardiovascular aging in kidney transplant recipients.
Article
Biochemistry & Molecular Biology
R. Mahalakshmi, J. Priyanga, Dipita Bhakta-Guha, Gunjan Guha
Summary: This study demonstrates that low doses of rapamycin can alleviate aging-associated mitochondrial dyshomeostasis in WRL-68 cells, such as oxidative damage to mitochondrial nucleic acids and proteins, as well as imbalance in mitochondrial density, membrane potential, biogenesis, mitophagy, and overall metabolism.
MOLECULAR BIOLOGY REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Juan A. Godoy, Juvenal A. Rios, Pol Picon-Pages, Victor Herrera-Fernandez, Bronte Swaby, Giulia Crepin, Ruben Vicente, Jose M. Fernandez-Fernandez, Francisco J. Munoz
Summary: Mitochondria play critical roles in neurons by regulating neurotransmission and synaptic plasticity through ATP supply, calcium homeostasis, redox balance control, and apoptosis. Their functional integrity is mainly maintained by mitostasis, involving processes like mitochondrial transport, anchoring, fusion, and fission, regulated by various signaling pathways. The communication between mitochondria and the endoplasmic reticulum (ER) via mitochondria-associated membranes (MAMs) is crucial for Ca2+ buffering. Alterations in mitochondrial activity can lead to increased production of reactive oxygen species, disturbance in physiological metabolism, and mitochondrial dysfunction resulting in cell death through apoptosis.
Review
Biochemistry & Molecular Biology
Roberto Cannataro, Leandro Carbone, Jorge L. Petro, Erika Cione, Salvador Vargas, Heidy Angulo, Diego A. Forero, Adrian Odriozola-Martinez, Richard B. Kreider, Diego A. Bonilla
Summary: Sarcopenia, an age-related decline in skeletal muscle mass and function, presents a significant impact on quality of life. Current research focuses on nutritional interventions primarily on protein intake, while the effects of other nutrition strategies remain unclear. A comprehensive nutritional approach and miRNAs may play crucial roles in mitigating the adverse effects of sarcopenia.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Lucia Jimenez, Carlos Amenabar, Victor Mayoral-Varo, Thomas A. Mackenzie, Maria C. Ramos, Andreia Silva, Giampaolo Calissi, Ines Grenho, Carmen Blanco-Aparicio, Joaquin Pastor, Diego Megias, Bibiana Ferreira, Wolfgang Link
Summary: FOXO proteins play important roles in cancer and aging, and their activity can be regulated through pharmacological manipulation. The study suggests that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.
Article
Biochemistry & Molecular Biology
Francesca Grisan, Liliana F. Iannucci, Nicoletta C. Surdo, Andrea Gerbino, Sofia Zanin, Giulietta Di Benedetto, Tullio Pozzan, Konstantinos Lefkimmiatis
Summary: Autophagy is a highly regulated degradative process crucial for maintaining cell homeostasis, with compartmentalization playing a key role. The involvement of localized signaling events, such as the cAMP/PKA cascade, in autophagy regulation presents a complex and cell type-dependent interplay. The study demonstrates that the effects of cAMP elevation on autophagy can vary between different cell types, highlighting the importance of sub-compartmentalization in signaling cascades.
CELL DEATH AND DIFFERENTIATION
(2021)
Article
Cell Biology
Mira Ham, Yeonju Cho, Tae-Wook Kang, Taeyun Oh, Hyoung-June Kim, Kyu-Han Kim
Summary: In this study, the researchers used weighted gene co-expression network analysis to identify aging-related marker genes in subcutaneous adipose tissue (SAT). They identified GYG2 as a novel key aging associated gene and found links between GYG2 and mitochondrial function as well as brown/beige adipocytes. They also identified PPARG as the transcription factor of GYG2 expression. These findings are important for determining the age of SAT and uncovering new mechanisms underlying SAT aging.
Review
Geriatrics & Gerontology
Steven N. Austad, Thomas W. Buford, David B. Allison, Scott. W. Ballinger, Andrew W. Brown, Christy S. Carter, Victor M. Darley-Usmar, John L. Hartman, Timothy R. Nagy, Daniel L. Smith, Liou Sun, Jianhua Zhang
Summary: The UAB Nathan Shock Center focuses on comparative energetics and aging, with a focus on the link between energetics and aging in terms of dysregulated mitochondrial function, altered metabolic signaling, and aberrant nutrient responsiveness with increasing age. The center offers world-class expertise in comprehensive energetic assessment and analysis, as well as state-of-the-art data analytics through its three research cores.
Article
Geriatrics & Gerontology
Kamil A. Kobak, Marcus M. Lawrence, Gavin Pharaoh, Agnieszka K. Borowik, Frederick F. Peelor, Patrick D. Shipman, Timothy M. Griffin, Holly Van Remmen, Benjamin F. Miller
Summary: This study demonstrated the importance of accounting for a change in protein mass during D2O labelling studies, while also exploring the contribution of protein synthesis and breakdown to denervation-induced muscle atrophy. Conflicting results were found between steady- and non-steady-state calculations on myofibrillar protein synthesis and breakdown during periods of muscle loss. Additionally, collagen accumulation was largely from a decrease in collagen breakdown during denervation.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Article
Geriatrics & Gerontology
P. La Padula, L. E. Costa, A. Karadayian, S. Lores-Arnaiz, A. Czerniczyniec
Summary: In old rats, acute hypobaric hypoxia leads to different responses in brain and heart mitochondria. The brain mitochondria show mild uncoupling and increased NO production, while the heart mitochondria decrease ROS production and NO production through increased cytochrome oxidase activity, suggesting a self-protective mechanism.
EXPERIMENTAL GERONTOLOGY
(2023)
Review
Cell Biology
Yuan Li, Laura Berliocchi, Zhiquan Li, Lene Juel Rasmussen
Summary: Current research on human aging has been guided by the hallmarks of aging proposed in 2013. Most studies have focused on individual hallmarks, but recent research has explored the complex interactions between multiple hallmarks and their effects over time. Understanding these interconnections will greatly benefit aging research and the development of effective interventions for promoting healthy aging.
Article
Neurosciences
Marisa A. Jeffries, Lauren E. McLane, Luipa Khandker, Marie L. Mather, Angelina V. Evangelou, Divyangi Kantak, Jennifer N. Bourne, Wendy B. Macklin, Teresa L. Wood
Summary: This study investigated the role of mTOR signaling in oligodendrocyte lineage during remyelination. The results showed that mTOR is required for metabolic function in cuprizone-demyelinated adult brain, influencing myelin production efficiency and myelin thickness during the repair process. Loss of mTOR in OPCs did not affect remyelination efficiency after other types of lesions, suggesting a specific function in cuprizone-induced demyelination.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Pei - Tsai, Ekaterina Korotkevich, Patrick H. O'Farrell
Summary: Unknown processes lead to accumulation of mitochondrial DNA mutations, which promote heteroplasmic mitochondrial diseases and degenerative changes with aging. Purifying selection operates during development and growth, but loses effectiveness during aging. Quality control pathways and pharmacological interventions can mitigate accumulation of deleterious mutations and improve health span.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Physiology
Justin A. Fletcher, Melissa A. Linden, Ryan D. Sheldon, Grace M. Meers, E. Matthew Morris, Anthony Butterfield, James W. Perfield, R. Scott Rector, John P. Thyfault
EXPERIMENTAL PHYSIOLOGY
(2018)
Article
Cell Biology
Adam R. Konopka, Jaime L. Laurin, Hayden M. Schoenberg, Justin J. Reid, William M. Castor, Christopher A. Wolff, Robert V. Musci, Oscar D. Safairad, Melissa A. Linden, Laurie M. Biela, Susan M. Bailey, Karyn L. Hamilton, Benjamin F. Miller
Article
Geriatrics & Gerontology
Christopher A. Wolff, Justin J. Reid, Robert V. Musci, Danielle R. Bruns, Melissa A. Linden, Adam R. Konopka, Frederick F. Peelor, Benjamin F. Miller, Karyn L. Hamilton
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2020)
Article
Endocrinology & Metabolism
Melissa A. Linden, Trenton T. Ross, David A. Beebe, Matthew F. Gorgoglione, Karyn L. Hamilton, Benjamin F. Miller, Barry Braun, William P. Esler
METABOLISM-CLINICAL AND EXPERIMENTAL
(2019)
Article
Endocrinology & Metabolism
Ryan D. Sheldon, Grace M. Meers, E. Matthew Morris, Melissa A. Linden, Rory P. Cunningham, Jamal A. Ibdah, John P. Thyfault, M. Harold Laughlin, R. Scott Rector
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2019)
Article
Geriatrics & Gerontology
Christopher A. Wolff, Marcus M. Lawrence, Hunter Porter, Qian Zhang, Justin J. Reid, Jaime L. Laurin, Robert V. Musci, Melissa A. Linden, Frederick F. Peelor, Jonathan D. Wren, Joseph S. Creery, Kyle J. Cutler, Richard H. Carson, John C. Price, Karyn L. Hamilton, Benjamin F. Miller
Summary: The study showed that Rapamycin and Rapamycin + Metformin have different effects on protein synthesis in young mice, with overall synthesis decreasing but individual synthesis rates varying. Metformin helps to balance the effects of Rapamycin on protein synthesis across different tissues and sexes, providing potential insights into how the combination may extend lifespan in both males and females.
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
Endocrinology & Metabolism
Tai-Yu Huang, Melissa A. Linden, Scott E. Fuller, Felicia R. Goldsmith, Jacob Simon, Heidi M. Batdorf, Matthew C. Scott, Nabil M. Essajee, John M. Brown, Robert C. Noland
Summary: Ketogenic diets with normal protein content (NPKD) increase body weight and fat mass, enhance intramuscular triglyceride storage, and upregulate pathways related to protein metabolism. When combined with exercise training, NPKD induces additive and/or synergistic activation of AMPK, PGC-1a, mitochondrial fission/fusion genes, and lipid oxidation pathways in skeletal muscle. These results provide mechanistic insight into adaptations in skeletal muscle relevant to keto-adaptation.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Neurosciences
Robert Musci, Kendra M. Andrie, Maureen A. Walsh, Zackary J. Valenti, Melissa A. Linden, Maryam F. Afzali, Sydney Bork, Margaret Campbell, Taylor Johnson, Thomas E. Kail, Richard Martinez, Tessa Nguyen, Joseph Sanford, Sara Wist, Meredith D. Murrell, Joe M. McCord, Brooks M. Hybertson, Qian Zhang, Martin A. Javors, Kelly S. Santangelo, Karyn L. Hamilton
Summary: This study investigated the effects of PB125 treatment on musculoskeletal decline in Hartley guinea pigs. The results showed that PB125 improved mitochondrial function and proteostasis in skeletal muscles, but did not significantly affect voluntary mobility. Further research is needed to determine if PB125 can also slow down the progression of other aspects of musculoskeletal dysfunction.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Editorial Material
Endocrinology & Metabolism
Melissa A. Linden, Susan J. Burke, Humza A. Pirzadah, Tai-Yu Huang, Heidi M. Batdorf, Walid K. Mohammed, Katarina A. Jones, Sujoy Ghosh, Shawn R. Campagna, J. Jason Collier, Robert C. Noland
Summary: Glucocorticoid therapy can cause iatrogenic diabetes, and activating lipolysis plays a crucial role in its development. Inhibiting lipolysis can reduce glucocorticoid-induced obesity and hyperglycemia. The role of lipolysis differs between skeletal muscle and liver.
MOLECULAR METABOLISM
(2023)
Review
Sport Sciences
Robert Musci, Karyn L. Hamilton, Melissa A. Linden
Article
Endocrinology & Metabolism
Laura C. Ortinau, Melissa A. Linden, Rebecca Dirkes, R. Scott Rector, Pamela S. Hinton
Article
Endocrinology & Metabolism
Laura C. Ortinau, Melissa A. Linden, Rebecca K. Dirkes, R. Scott Rector, Pamela S. Hinton
Article
Nutrition & Dietetics
Laura C. Ortinau, Melissa A. Linden, R. Scott Rector, Pamela S. Hinton
APPLIED PHYSIOLOGY NUTRITION AND METABOLISM
(2017)