Review
Cell Biology
Mario G. Mirisola, Valter D. Longo
Summary: S. cerevisiae plays a crucial role as a model organism in understanding mammalian biochemistry and molecular biology. The study of its chronological lifespan provides insights into age-related damage and longevity extension. It also serves as a model system to study macromolecular and cellular damage leading to diseases and investigate the effects of nutrients and dietary regimens on stress resistance and longevity.
Article
Genetics & Heredity
Luisa F. F. Pallares, Amanda J. J. Lea, Clair Han, Elena V. V. Filippova, Peter Andolfatto, Julien F. F. Ayroles
Summary: Evolutionary theory suggests that lifespan-reducing alleles should be eliminated, but studies have shown that they persist. This study found that alleles regulating lifespan have context-dependent effects and a third of lifespan-associated genetic variation is influenced by the environment. Lifespan-reducing alleles are often recent, have stronger effects on a high-sugar diet, and show signs of selection in wild populations, supporting the evolutionary mismatch hypothesis. These findings provide insights into the complex genetic architecture of lifespan and the evolutionary processes that shape it.
Article
Biochemistry & Molecular Biology
Yongxuan Li, Wei Zhang, Yunshuang Ye, Yinan Sun, Liping Yang, Guijun Chen, Kangning Chen, Sheryl Smith, Jumin Zhou
Summary: Autophagy has important and complex roles in aging, affecting health and longevity. This study showed that the levels of ATG4B and ATG4D decrease with aging in the general population, but are upregulated in centenarians, suggesting a positive effect on healthspan and lifespan. Overexpression of Atg4b in Drosophila increased resistance to oxidative and desiccation stress, improved fitness, and increased lifespan. Overexpression of ATG4B delayed cellular senescence and improved cell proliferation. These findings suggest that targeting ATG4D and ATG4B could be beneficial for health and lifespan interventions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Lindsay E. Wu, Corrine E. Fiveash, Nicholas L. Bentley, Myung-Jin Kang, Hemna Govindaraju, Jayne A. Barbour, Brendan P. Wilkins, Sarah E. Hancock, Romanthi Madawala, Abhijit Das, Hassina Massudi, Catherine Li, Lynn-Jee Kim, Ashley S. A. Wong, Maria B. Marinova, Ghazal Sultani, Abhirup Das, Neil A. Youngson, David G. Le Couteur, David A. Sinclair, Nigel Turner
Summary: The NAD+-dependent deacylase family of sirtuin enzymes, including SIRT2, play important roles in biological aging, late-life health, and overall lifespan. However, the role of SIRT2 has been less clear. Previous studies showed that transgenic overexpression of SIRT2 can improve health and increase lifespan in a progeria model. In this study, the researchers tested whether SIRT2 overexpression would impact the overall health and lifespan of mice on a nonprogeroid, wild-type background. They found that SIRT2 overexpression did not have an additional impact on health or lifespan in these mice. Biochemical studies also revealed changes in brain metabolites in SIRT2 overexpressing mice, but these changes did not translate into functional differences.
Article
Geriatrics & Gerontology
Wei Zhang, Yunshuang Ye, Yinan Sun, Yongxuan Li, Mingxia Ge, Kangning Chen, Liping Yang, Guijun Chen, Jumin Zhou
Summary: Aging is associated with weakened immune function, but dietary restriction can improve health and lifespan. Halving amino acid components in the HUNTaa diet further extends lifespan and improves resistance. In aged fruit flies, stress-related genes are downregulated and immune function is enhanced, reducing immune senescence.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2023)
Review
Cell Biology
Olatunde Omotoso, Vadim N. Gladyshev, Xuming Zhou
Summary: Evidence suggests that long-lived animals achieve longevity through adaptive genetic changes that modify physiological functions. The longevity effects generated by adaptive or adaptation-linked mutations/substitutions are nonrandom and favored indirectly by natural selection. These findings highlight the importance of decoding genetic factors of lifespan control.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Review
Cell Biology
Zheng Zhou, Bao Sun, Dongsheng Yu, Meng Bian
Summary: tRNAs, traditionally seen as housekeepers, are now known to play important roles in various physiological and pathological processes, including aging and lifespan regulation.
CELL DEATH & DISEASE
(2021)
Article
Multidisciplinary Sciences
Hannah Froy, Sarah L. Underwood, Jennifer Dorrens, Luise A. Seeker, Kathryn Watt, Rachael V. Wilbourn, Jill G. Pilkington, Lea Harrington, Josephine M. Pemberton, Daniel H. Nussey
Summary: The study found that in wild Soay sheep, there was no significant association between telomere length and subsequent survival, suggesting that telomere length is not an important marker of biological aging or exposure to environmental stress in this study system. Instead, individual differences in average telomere length were associated with increased lifespan, indicating a genetic basis for this correlation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Review
Physiology
Corinne Hutfilz
Summary: Diapause is a physiological adaptation that allows animals to survive and conserve energy in unfavorable conditions. This adaptation is regulated by endocrine signaling, particularly in insect diapause. Recent research suggests a possible overlap between diapause endocrinology and the biology of aging, providing insights into lifespan determination.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Cell Biology
Dominic F. Bennett, Anita Goyala, Cyril Statzer, Charles W. Beckett, Alexander Tyshkovskiy, Vadim N. Gladyshev, Collin Y. Ewald, Joao Pedro de Magalhaes
Summary: Searching for drugs with similar gene expression patterns, rilmenidine was found to extend the lifespan of nematodes and rats, mediated by the I1-imidazoline receptor. This study suggests the potential of rilmenidine as a longevity-promoting drug.
Article
Cell Biology
Thais R. Peclat, Katie L. Thompson, Gina M. Warner, Claudia C. S. Chini, Mariana G. Tarrago, Delaram Z. Mazdeh, Chunlian Zhang, Jose Zavala-Solorio, Ganesh Kolumam, Yao Liang Wong, Robert L. Cohen, Eduardo N. Chini
Summary: Inhibiting CD38 enzyme can prolong the lifespan and healthspan of aged mice, improve exercise performance, endurance, and metabolic function, with differences observed between sexes.
Article
Cell Biology
Quentin Alle, Enora Le Borgne, Paul Bensadoun, Camille Lemey, Nelly Bechir, Melissa Gabanou, Fanny Estermann, Christelle Bertrand-Gaday, Laurence Pessemesse, Karine Toupet, Romain Desprat, Jerome Vialaret, Christophe Hirtz, Daniele Noel, Christian Jorgensen, Francois Casas, Ollivier Milhavet, Jean-Marc Lemaitre
Summary: Recent studies on cell reprogramming have shown that a short induction of OSKM can improve cell physiology and prevent musculoskeletal deterioration in mice. This treatment also improves tissue structures in various organs and increases lifespan by 15% through rejuvenation of age-related DNA methylation signatures.
Article
Multidisciplinary Sciences
Manuel Hotz, Nathaniel H. Thayer, David G. Hendrickson, Elizabeth L. Schinski, Jun Xu, Daniel E. Gottschling
Summary: This study discovered a previously unappreciated relationship between the number of copies of the ribosomal RNA gene and the replicative lifespan in budding yeast. The data suggest that regulatory mechanisms involving ribosomal DNA copy number limit lifespan and changes in rDNA copy number might explain the effects of lifespan-enhancing mutations.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biotechnology & Applied Microbiology
Yingying Wang, Zhen Zhu, Ke Liu, Qin Xiao, Yangye Geng, Feng Xu, Shuiping Ouyang, Ke Zheng, Yimin Fan, Nan Jin, Xiangwei Zhao, Mario A. Marchisio, Dejing Pan, Qing-An Huang
Summary: In this study, a high-throughput microfluidic chip for diploid yeast long-term culturing, optical inspection, and cell-aging analysis was developed. The chip features delicate microstructures to ensure cell stability and alleviate stress. Using this chip, the researchers were able to track the replicative lifespan and budding time interval of diploid yeast cells and observe cell desynchronization during aging.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Review
Cell Biology
Hokuto Ohtsuka, Takafumi Shimasaki, Hirofumi Aiba
Summary: The mechanism of longevity control in unicellular organisms shows evolutionary conservation with higher multicellular organisms. Research on chronological lifespan of fission yeast Schizosaccharomyces pombe has identified multiple compounds, nutrient restrictions, and genes that extend lifespan. These mechanisms involve nutritional response, stress responses, autophagy, and other pathways, suggesting a link between lifespan control and resource management in unicellular organisms.
Article
Cell Biology
Dominic F. Bennett, Anita Goyala, Cyril Statzer, Charles W. Beckett, Alexander Tyshkovskiy, Vadim N. Gladyshev, Collin Y. Ewald, Joao Pedro de Magalhaes
Summary: Searching for drugs with similar gene expression patterns, rilmenidine was found to extend the lifespan of nematodes and rats, mediated by the I1-imidazoline receptor. This study suggests the potential of rilmenidine as a longevity-promoting drug.
Article
Biochemistry & Molecular Biology
Alexander Tyshkovskiy, Siming Ma, Anastasia Shindyapina, Stanislav Tikhonov, Sang-Goo Lee, Perinur Bozaykut, Jose P. Castro, Andrei Seluanov, Nicholas J. Schork, Vera Gorbunova, Sergey E. Dmitriev, Richard A. Miller, Vadim N. Gladyshev
Summary: By analyzing the RNA-seq data of 41 mammalian species, this study identifies longevity signatures and their relationship with aging biomarkers and lifespan-extending interventions. The study reveals shared and unique mechanisms of lifespan regulation within and across species, and provides insights into discovering longevity interventions. The findings suggest the downregulated Igf1 and upregulated mitochondrial translation genes as universal longevity mechanisms, and highlight the distinct regulation of innate immune response and cellular respiration.
Article
Cell Biology
Jesse R. Poganik, Bohan Zhang, Gurpreet S. Baht, Alexander Tyshkovskiy, Amy Deik, Csaba Kerepesi, Sun Hee Yim, Ake T. Lu, Amin Haghani, Tong Gong, Anna M. Hedman, Ellika Andolf, Goran Pershagen, Catarina Almqvist, Clary B. Clish, Steve Horvath, James P. White, Vadim N. Gladyshev
Summary: Aging is traditionally seen as a steady process of accumulating damage and loss of function, but recent studies have suggested the possibility of age reversal. This study found that biological age can change rapidly in response to different stressors, including surgery, pregnancy, and severe COVID-19. The elevation of biological age by stress is reversible, indicating that it is a dynamic process. Understanding the dynamics of aging can inform future interventions targeted at reducing stress-induced aging.
Article
Oncology
Sara Lindstrom, Lu Wang, Helian Feng, Arunabha Majumdar, Sijia Huo, James Macdonald, Tabitha Harrison, Constance Turman, Hongjie Chen, Nicholas Mancuso, Theo Bammler, Steve Gallinger, Stephen B. Gruber, Marc J. Gunter, Loic Le Marchand, Victor Moreno, Kenneth Offit, Immaculata De Vivo, Tracy A. O'Mara, Amanda B. Spurdle, Ian Tomlinson, Rebecca Fitzgerald, Puya Gharahkhani, Ines Gockel, Janusz Jankowski, Stuart Macgregor, Johannes Schumacher, Jill Barnholtz-Sloan, Melissa L. Bondy, Richard S. Houlston, Robert B. Jenkins, Beatrice Melin, Margaret Wrensch, Paul Brennan, David C. Christiani, Mattias Johansson, James Mckay, Melinda C. Aldrich, Christopher Amos, Maria Teresa Landi, Adonina Tardon, D. Timothy Bishop, Florence Demenais, Alisa M. Goldstein, Mark M. Iles, Peter A. Kanetsky, Matthew H. Law, Laufey T. Amundadottir, Rachael Stolzenberg-Solomon, Brian M. Wolpin, Alison Klein, Gloria Petersen, Harvey Risch, Stephen J. Chanock, Mark P. Purdue, Ghislaine Scelo, Paul Pharoah, Siddhartha Kar, Rayjean J. Hung, Bogdan Pasaniuc, Peter Kraft
Summary: This study quantified the shared genetic contribution to risk of different cancers and identified novel cancer susceptibility loci using data from 12 cancer genome-wide association studies. The results suggest that some genetic risk variants are shared among cancers, but most of cancer heritability is specific to certain tissues. Cross-disease analysis allows for increased statistical power and the identification of new susceptibility regions. Future studies are likely to discover additional regions associated with the risk of multiple cancer types.
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
(2023)
Article
Cell Biology
Xuanjing Li, Pengcheng Wang, Qi Pan, Gaoming Liu, Weiqiang Liu, Olatunde Omotoso, Juan Du, Zihao Li, Yang Yu, Yun Huang, Pingfen Zhu, Meng Li, Xuming Zhou
Summary: This study generated a high-quality genome of the Asian elephant and identified expanded gene families related to tumor-associated pathways. Comparative genomic analysis revealed genes with positive selection in long-lived mammals, which enhanced the inhibition of tumor cell migration.
Article
Biochemistry & Molecular Biology
Weiqiang Liu, Pingfen Zhu, Meng Li, Zihao Li, Yang Yu, Gaoming Liu, Juan Du, Xiao Wang, Jing Yang, Ran Tian, Inge Seim, Alaattin Kaya, Mingzhou Li, Ming Li, Vadim N. Gladyshev, Xuming Zhou
Summary: The variation in lifespan among mammals is significant, and the study aims to uncover the evolutionary forces and molecular features related to longevity. Comparative transcriptomics analysis of liver, kidney, and brain tissues of 103 mammalian species revealed that only a few genes have common expression patterns with longevity. However, pathways related to translation fidelity and methionine restriction showed correlation with lifespan. The study suggests that lifespan regulation through gene expression is driven by polygenic and indirect natural selection.
Article
Neurosciences
Morteza Abyadeh, Vijay K. Yadav, Alaattin Kaya
Summary: This study analyzed transcriptome data from 638 brain samples and identified common gene and pathway changes in the frontal cortex of COVID-19 and AD patients. Downregulation of the cAMP signaling pathway, taurine metabolism, and upregulation of neuroinflammatory pathways may contribute to cognitive decline and AD in COVID-19 patients. Additionally, potential genetic targets for pharmaceutical intervention were identified to reduce the risk or delay the development of COVID-19-related neurological pathologies and AD.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Article
Multidisciplinary Sciences
Zhihui Zhang, Xiao Tian, J. Yuyang Lu, Kathryn Boit, Julia Ablaeva, Frances Tolibzoda Zakusilo, Stephan Emmrich, Denis Firsanov, Elena Rydkina, Seyed Ali Biashad, Quan Lu, Alexander Tyshkovskiy, Vadim N. Gladyshev, Steve Horvath, Andrei Seluanov, Vera Gorbunova
Summary: Abundant high-molecular-mass hyaluronic acid (HMM-HA) contributes to cancer resistance and longevity in naked mole-rats. A study showed that overexpressing the naked mole-rat hyaluronic acid synthase 2 gene (nmrHas2) in mice resulted in increased hyaluronan levels, reduced incidence of cancer, extended lifespan, and improved healthspan. The beneficial effects were mediated by HMM-HA and not specific to the nmrHas2 gene, suggesting that the longevity mechanism observed in naked mole-rats can be transferred to other species.
Article
Endocrinology & Metabolism
Alessandro Bitto, Anthony S. Grillo, Takashi K. Ito, Ian B. Stanaway, Bao M. G. Nguyen, Kejun Ying, Herman Tung, Kaleb Smith, Ngoc Tran, Gunnar Velikanje, Silvan R. Urfer, Jessica M. Snyder, Jacob Barton, Ayush Sharma, Ernst-Bernhard Kayser, Lu Wang, Daniel L. Smith, J. Will Thompson, Laura DuBois, William DePaolo, Matt Kaeberlein
Summary: Treatment with acarbose or antibiotics that alter the gut microbiome can extend healthspan and lifespan in a mouse model of Leigh syndrome. Mitochondrial diseases and biological ageing share common mechanisms, and drugs like rapamycin and acarbose can improve survival and reduce symptoms in Leigh syndrome mice. Unlike rapamycin, acarbose can rescue disease phenotypes without inhibiting the mechanistic target of rapamycin.
Article
Cell Biology
Bohan Zhang, David E. Lee, Alexandre Trapp, Alexander Tyshkovskiy, Ake T. Lu, Akshay Bareja, Csaba Kerepesi, Lauren K. McKay, Anastasia V. Shindyapina, Sergey E. Dmitriev, Gurpreet S. Baht, Steve Horvath, Vadim N. Gladyshev, James P. White
Summary: Heterochronic parabiosis (HPB) is a technique that has rejuvenation effects on mouse tissues, reducing biological age and improving long-term health. In this study, mice exposed to young circulation through HPB showed reduced epigenetic aging, and this effect lasted even after the removal of youthful circulation. The transcriptomic and epigenomic profiles of these mice indicated a global rejuvenation effect. Furthermore, gene expression changes in the old HPB mice resembled those seen in interventions that extend lifespan. Overall, HPB results in lasting changes in epigenetic and transcriptomic profiles, leading to an extension of lifespan and health span.
Article
Geriatrics & Gerontology
Cheryl Zi Jin Phua, Xiaqing Zhao, Lesly Turcios-Hernandez, Morrigan McKernan, Morteza Abyadeh, Siming Ma, Daniel Promislow, Matt Kaeberlein, Alaattin Kaya
Summary: In this study, the researchers investigated the relationship between altered mitochondrial function and lifespan regulation using yeast knock-out strains. They found that inhibition of different nuclear-coded mitochondrial genes attenuated a common mechanism that controls certain cellular processes and regulates lifespan. These findings may have implications for understanding lifespan regulation in more complex organisms.
Article
Cell Biology
Trisha A. Staab, Grace McIntyre, Lu Wang, Joycelyn Radeny, Lisa Bettcher, Melissa Guillen, Margaret P. Peck, Azia P. Kalil, Samantha P. Bromley, Daniel Raftery, Jason P. Chan
Summary: Lipid metabolism plays a crucial role in cell functions and animal lifespan. Utilizing lipidomics approaches in the model organism C. elegans, this study examined changes in lipid composition related to age and lifespan. Mutants lacking enzymes critical for sphingolipid metabolism were analyzed, revealing differences in lipid profiles compared to wild type animals. These findings provide insights into the metabolic changes during aging in C. elegans and highlight the importance of lipidomic analyses.
Article
Cell Biology
Ian Matthews, Allison Birnbaum, Anastasia Gromova, Amy W. Huang, Kailin Liu, Eleanor A. Liu, Kristen Coutinho, Megan Mcgraw, Dalton C. Patterson, Macy T. Banks, Amber C. Nobles, Nhat Nguyen, Gennifer E. Merrihew, Lu Wang, Eric Baeuerle, Elizabeth Fernandez, Nicolas Musi, Michael J. Maccoss, Helen C. Miranda, Albert R. La Spada, Constanza J. Cortes
Summary: Recent research has shown that skeletal muscle can regulate central nervous system function and aging by secreting myokines. A study on transgenic mice with enhanced skeletal muscle lysosomal and mitochondrial function through targeted overexpression of transcription factor E-B (TFEB) found that it reduces neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tauopathy. Muscle-specific TFEB overexpression significantly ameliorates proteotoxicity, reduces neuroinflammation, and promotes transcriptional remodeling of the aged central nervous system, preserving cognition and memory in aged mice.
Article
Cell Biology
Julio Aguado, Alberto A. Amarilla, Atefeh Taherian Fard, Eduardo A. Albornoz, Alexander Tyshkovskiy, Marius Schwabenland, Harman K. Chaggar, Naphak Modhiran, Cecilia Gomez-Inclan, Ibrahim Javed, Alireza A. Baradar, Benjamin Liang, Lianli Peng, Malindrie Dharmaratne, Giovanni Pietrogrande, Pranesh Padmanabhan, Morgan E. Freney, Rhys Parry, Julian D. J. Sng, Ariel Isaacs, Alexander A. Khromykh, Guillermo Valenzuela Nieto, Alejandro Rojas-Fernandez, Thomas P. Davis, Marco Prinz, Bertram Bengsch, Vadim N. Gladyshev, Trent M. Woodruff, Jessica C. Mar, Daniel Watterson, Ernst J. Wolvetang
Summary: Senescent cells play a significant role in brain aging and COVID-19-induced neuropathology, and senolytic therapy shows therapeutic potential in protecting against COVID-19-induced brain aging.