Viviane Fleischhacker, Filip Milosic, Marko Bricelj, Kristina Kührer, Katharina Wahl-Figlash, Patrick Heimel, Andreas Diendorfer, Eleonora Nardini, Irmgard Fischer, Herbert Stangl, Peter Pietschmann, Matthias Hackl, Roland Foisner, Johannes Grillari, Markus Hengstschläger, Selma Osmanagic-Myers
Age-induced decline in osteogenic potential of bone marrow mesenchymal stem cells (BMSCs) potentiates osteoporosis and increases the risk for bone fractures. Despite epidemiology studies reporting concurrent development of vascular and bone diseases in the elderly, the underlying mechanisms for the vascular-bone cross-talk in aging are largely unknown. In this study, we show that accelerated endothelial aging deteriorates bone tissue through paracrine repression of Wnt-driven-axis in BMSCs. Here, we utilize physiologically aged mice in conjunction with our transgenic endothelial progeria mouse model (Hutchinson-Gilford progeria syndrome; HGPS) that displays hallmarks of an aged bone marrow vascular niche...
April 5, 2024: Aging Cell
Mzwanele Ngubo, Zhaoyi Chen, Darin McDonald, Rana Karimpour, Amit Shrestha, Julien Yockell-Lelièvre, Aurélie Laurent, Ojong Tabi Ojong Besong, Eve C Tsai, F Jeffrey Dilworth, Michael J Hendzel, William L Stanford
Hutchinson-Gilford Progeria syndrome (HGPS) is a lethal premature aging disorder caused by a de novo heterozygous mutation that leads to the accumulation of a splicing isoform of Lamin A termed progerin. Progerin expression deregulates the organization of the nuclear lamina and the epigenetic landscape. Progerin has also been observed to accumulate at low levels during normal aging in cardiovascular cells of adults that do not carry genetic mutations linked with HGPS. Therefore, the molecular mechanisms that lead to vascular dysfunction in HGPS may also play a role in vascular aging-associated diseases, such as myocardial infarction and stroke...
April 4, 2024: Aging Cell
Rui Mao, Ji Li, Wenqin Xiao
Aging represents a multifaceted process culminating in the deterioration of biological functions. Despite the introduction of numerous anti-aging strategies, their therapeutic outcomes have often been less than optimal. Consequently, discovering new targets to mitigate aging effects is of critical importance. We applied Mendelian randomization (MR) to identify potential pharmacological targets against aging, drawing upon summary statistics from both the Decode and FinnGen cohorts, with further validation in an additional cohort...
April 4, 2024: Aging Cell
Hao-Tian Wang, Fu-Hui Xiao, Zong-Liang Gao, Li-Yun Guo, Li-Qin Yang, Gong-Hua Li, Qing-Peng Kong
The transition from ordered to noisy is a significant epigenetic signature of aging and age-related disease. As a paradigm of healthy human aging and longevity, long-lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high-resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs...
April 2, 2024: Aging Cell
Guorong Li, Joseph van Batenburg-Sherwood, Babak N Safa, Nina Sara Fraticelli Guzmán, Andrea Wilson, Mohammad Reza Bahrani Fard, Kevin Choy, Michael L de Ieso, J Serena Cui, Andrew J Feola, Tara Weisz, Megan Kuhn, Catherine Bowes Rickman, Sina Farsiu, C Ross Ethier, W Daniel Stamer
Age and elevated intraocular pressure (IOP) are the two primary risk factors for glaucoma, an optic neuropathy that is the leading cause of irreversible blindness. In most people, IOP is tightly regulated over a lifetime by the conventional outflow tissues. However, the mechanistic contributions of age to conventional outflow dysregulation, elevated IOP and glaucoma are unknown. To address this gap in knowledge, we studied how age affects the morphology, biomechanical properties and function of conventional outflow tissues in C57BL/6 mice, which have an outflow system similar to humans...
April 2, 2024: Aging Cell
Zhuo Yu, Yushan Dong, Yuhan Chen, Lotfi Aleya, Yinhuan Zhao, Lan Yao, Weikuan Gu
A recently proposed principal law of lifespan (PLOSP) proposes to extend the whole human lifespan by elongating different life stages. As the preborn stage of a human being, gestation is the foundation for the healthy development of the human body. The antagonistic pleiotropy (AP) theory of aging states that there is a trade-off between early life fitness and late-life mortality. The question is whether slower development during the gestation period would be associated with a longer lifespan. Among all living creatures, the length of the gestation period is highly positively correlated to the length of the lifespan, although such a correlation is thought to be influenced by the body sizes of different species...
April 1, 2024: Aging Cell
Xuanyang Wang, Xuemin Yan, Mengdi Li, Licheng Cheng, Xiang Qi, Jia Zhang, Sijia Pan, Xiaoqing Xu, Wei Wei, Ying Li
Previous research on sleep and aging largely has failed to illustrate the optimal dose-response curve of this relationship. We aimed to analyze the associations between sleep duration and measures of predicted age. In total, 241,713 participants from the UK Biobank were included. Habitual sleep duration was collected from the baseline questionnaire. Four indicators, homeostatic dysregulation (HD), phenoAge (PA), Klemera-Doubal method (KDM), and allostatic load (AL), were chosen to assess predicted age. Multivariate linear regression models were utilized...
March 31, 2024: Aging Cell
Du Hyun Ro, Gun Hee Cho, Ji Yoon Kim, Seong Ki Min, Ha Ru Yang, Hee Jung Park, Sun Young Wang, You Jung Kim, Myung Chul Lee, Hyun Cheol Bae, Hyuk-Soo Han
Senescent cells increase in many tissues with age and induce age-related pathologies, including osteoarthritis (OA). Senescent chondrocytes (SnCs) are found in OA cartilage, and the clearance of those chondrocytes prevents OA progression. However, targeting SnCs is challenging due to the absence of a senescent chondrocyte-specific marker. Therefore, we used flow cytometry to screen and select senescent chondrocyte surface markers and cross-validated with published transcriptomic data. Chondrocytes expressing dipeptidyl peptidase-4 (DPP-4), the selected senescent chondrocyte-specific marker, had multiple senescence phenotypes, such as increased senescence-associated-galactosidase, p16, p21, and senescence-associated secretory phenotype expression, and showed OA chondrocyte phenotypes...
March 31, 2024: Aging Cell
Thais Cardoso Bitencourt, Jose Eduardo Vargas, Andrew Oliveira Silva, Lucas Rosa Fraga, Eduardo Filippi-Chiela
Cellular senescence is a state of permanent growth arrest. It can be triggered by telomere shortening (replicative senescence) or prematurely induced by stresses such as DNA damage, oncogene overactivation, loss of tumor suppressor genes, oxidative stress, tissue factors, and others. Advances in techniques and experimental designs have provided new evidence about the biology of senescent cells (SnCs) and their importance in human health and disease. This review aims to describe the main aspects of SnCs phenotype focusing on alterations in subcellular compartments like plasma membrane, cytoskeleton, organelles, and nuclei...
March 30, 2024: Aging Cell
Nathan K LeBrasseur
No abstract text is available yet for this article.
March 27, 2024: Aging Cell
Zhengyuan Bao, Can Cui, Chaoran Liu, Yufeng Long, Ronald Man Yeung Wong, Senlin Chai, Ling Qin, Clinton Rubin, Benjamin Hon Kei Yip, Zhihong Xu, Qing Jiang, Simon Kwoon-Ho Chow, Wing-Hoi Cheung
Neuromuscular junction (NMJ) degeneration is one of pathological factors of sarcopenia. Low-magnitude high-frequency vibration (LMHFV) was reported effective in alleviating the sarcopenia progress. However, no previous study has investigated treatment effects of LMHFV targeting NMJ degeneration in sarcopenia. We first compared morphological differences of NMJ between sarcopenic and non-sarcopenic subjects, as well as young and old C57BL/6 mice. We then systematically characterized the age-related degeneration of NMJ in SAMP8 against its control strain, SAMR1 mice, from 3 to 12 months old...
March 27, 2024: Aging Cell
Noelia Morales-Prieto, Rebekah Bevans, Adam O'Mahony, Aaron Barron, Conor Giles Doran, Erin McCarthy, Ruth M Concannon, Susan R Goulding, Cathal M McCarthy, Louise M Collins, Aideen M Sullivan, Gerard W O'Keeffe
Parkinson's disease (PD) is characterised by progressive loss of dopaminergic (DA) neurons from the substantia nigra (SN) and α-synuclein (αSyn) accumulation. Age is the biggest risk factor for PD and may create a vulnerable pre-parkinsonian state, but the drivers of this association are unclear. It is known that ageing increases αSyn expression in DA neurons and that this may alter molecular processes that are central to maintaining nigrostriatal integrity. To model this, adult female Sprague-Dawley rats received a unilateral intranigral injection of adeno-associated viral (AAV) vector carrying wild-type human αSyn (AAV-αSyn) or control vector (AAV-Null)...
March 26, 2024: Aging Cell
Seokjin Ham, Sieun S Kim, Sangsoon Park, Hyunwoo C Kwon, Seokjun G Ha, Yunkyu Bae, Gee-Yoon Lee, Seung-Jae V Lee
Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with daf-2/insulin/IGF-1 receptor mutant Caenorhabditis elegans...
March 26, 2024: Aging Cell
Brendan Miller, Su-Jeong Kim, Kevin Cao, Hemal H Mehta, Neehar Thumaty, Hiroshi Kumagai, Tomomitsu Iida, Cassandra McGill, Christian J Pike, Kamila Nurmakova, Zachary A Levine, Patrick M Sullivan, Kelvin Yen, Nilüfer Ertekin-Taner, Gil Atzmon, Nir Barzilai, Pinchas Cohen
The APOE4 allele is recognized as a significant genetic risk factor to Alzheimer's disease (AD) and influences longevity. Nonetheless, some APOE4 carriers exhibit resistance to AD even in advanced age. Humanin, a mitochondrial-derived peptide comprising 24 amino acids, has variants linked to cognitive resilience and longevity. Our research uncovered a unique humanin variant, P3S, specifically enriched in centenarians with the APOE4 allele. Through in silico analyses and subsequent experimental validation, we demonstrated a strong affinity between humanin P3S and APOE4...
March 22, 2024: Aging Cell
Soo Young Jun, Hyang Ran Yoon, Ji-Yong Yoon, Jeong-Ju Lee, Ji Yeon Kim, Jin-Man Kim, Nam-Soon Kim
As people age, the risk and progression of colorectal cancer (CRC), along with cholesterol levels, tend to increase. Nevertheless, epidemiological studies on serum lipids and CRC have produced conflicting results. We previously demonstrated that the reduction of squalene epoxidase (SQLE) due to accumulated cholesterol within cells accelerates CRC progression through the activation of the β-catenin pathway. This study aimed to investigate the mechanism by which age-related cholesterol accumulation within tissue accelerates CRC progression and to assess the clinical significance of SQLE in older individuals with elevated CRC risk...
March 22, 2024: Aging Cell
Clara L Neal, William A Kronert, Jared Rafael T Camillo, Jennifer A Suggs, Tom Huxford, Sanford I Bernstein
The molecular motor myosin is post-translationally modified in its globular head, its S2 hinge, and its thick filament domain during human skeletal muscle aging. To determine the importance of such modifications, we performed an integrative analysis of transgenic Drosophila melanogaster expressing myosin containing post-translational modification mimic mutations. We determined effects on muscle function, myofibril structure, and myosin biochemistry. Modifications in the homozygous state decreased jump muscle function by a third at 3 weeks of age and reduced indirect flight muscle function to negligible levels in young flies, with severe effects on flight muscle myofibril assembly and/or maintenance...
March 20, 2024: Aging Cell
Mattheus Xing Rong Foo, Peh Fern Ong, Zi Xuan Yap, Martina Maric, Christopher Jue Shi Bong, Peter Dröge, Brian Burke, Oliver Dreesen
Hutchinson-Gilford Progeria syndrome (HGPS) is a severe premature ageing disorder caused by a 50 amino acid truncated (Δ50AA) and permanently farnesylated lamin A (LA) mutant called progerin. On a cellular level, progerin expression leads to heterochromatin loss, impaired nucleocytoplasmic transport, telomeric DNA damage and a permanent growth arrest called cellular senescence. Although the genetic basis for HGPS has been elucidated 20 years ago, the question whether the Δ50AA or the permanent farnesylation causes cellular defects has not been addressed...
March 19, 2024: Aging Cell
Waylon J Hastings, Qiaofeng Ye, Sarah E Wolf, Calen P Ryan, Sai Krupa Das, Kim M Huffman, Michael S Kobor, William E Kraus, Julia L MacIsaac, Corby K Martin, Susan B Racette, Leanne M Redman, Daniel W Belsky, Idan Shalev
Caloric restriction (CR) modifies lifespan and aging biology in animal models. The Comprehensive Assessment of Long-Term Effects of Reducing Intake of Energy (CALERIE™) 2 trial tested translation of these findings to humans. CALERIE™ randomized healthy, nonobese men and premenopausal women (age 21-50y; BMI 22.0-27.9 kg/m2 ), to 25% CR or ad-libitum (AL) control (2:1) for 2 years. Prior analyses of CALERIE™ participants' blood chemistries, immunology, and epigenetic data suggest the 2-year CR intervention slowed biological aging...
March 19, 2024: Aging Cell
Zachary J Fennel, Paul-Emile Bourrant, Anu Susan Kurian, Jonathan J Petrocelli, Naomi M M P de Hart, Elena M Yee, Sihem Boudina, Hans S Keirstead, Gabrielle Nistor, Scott A Greilach, Nicole C Berchtold, Thomas E Lane, Micah J Drummond
Aging coincides with the progressive loss of muscle mass and strength, increased adiposity, and diminished physical function. Accordingly, interventions aimed at improving muscle, metabolic, and/or physical health are of interest to mitigate the adverse effects of aging. In this study, we tested a stem cell secretome product, which contains extracellular vesicles and growth, cytoskeletal remodeling, and immunomodulatory factors. We examined the effects of 4 weeks of 2×/week unilateral intramuscular secretome injections (quadriceps) in ambulatory aged male C57BL/6 mice (22-24 months) compared to saline-injected aged-matched controls...
March 18, 2024: Aging Cell
Ya Wang, Hui Qiu, Shipeng Chen, Dongmei Li, Xu Zhao, Mengmeng Guo, Nana Li, Chao Chen, Ming Qin, Ya Zhou, Daimin Xiao, Juanjuan Zhao, Lin Xu
Aging is intricately linked to immune system dysfunction. Recent studies have highlighted the biological function of microRNA-7 (miR-7) as a novel regulator of immune cell function and related diseases. However, the potential role of miR-7 in aging remains unexplored. Here, we investigated the contribution of miR-7 to d-gal-induced aging in mice, focusing on its regulation of senescent Kupffer cells. Our findings revealed that miR-7 deficiency significantly ameliorated the aging process, characterized by enhanced CD4+ T-cell activation...
March 17, 2024: Aging Cell
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