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Ageing Research Reviews Apr 2024Osteoarthritis (OA), a chronic joint disease affecting millions of people aged over 65 years, is the main musculoskeletal cause of diminished joint mobility in the... (Review)
Review
Osteoarthritis (OA), a chronic joint disease affecting millions of people aged over 65 years, is the main musculoskeletal cause of diminished joint mobility in the elderly. It is characterized by lingering pain and increasing deterioration of articular cartilage. Aging and accumulation of senescent cells (SCs) in the joints are frequently associated with OA. Apoptosis resistance; irreversible cell cycle arrest; increased p16INK4a expression, secretion of senescence-associated secretory phenotype factors, senescence-associated β-galactosidase levels, secretion of extracellular vesicles, and levels of reactive oxygen and reactive nitrogen species; and mitochondrial dysregulation are some common changes in cellular senescence in joint tissues. Development of OA correlates with an increase in the density of SCs in joint tissues. Senescence-associated secretory phenotype has been linked to OA and cartilage breakdown. Senolytics and therapeutic pharmaceuticals are being focused upon for OA management. SCs can be selectively eliminated or killed by senolytics to halt the pathogenesis and progression of OA. Comprehensive understanding of how aging affects joint dysfunction will benefit OA patients. Here, we discuss age-related mechanisms associated with OA pathogenesis and senolytics as an emerging modality in the management of age-related SCs and pathogenesis of OA in preclinical and clinical studies.
Topics: Aged; Humans; Senotherapeutics; Osteoarthritis; Aging; Cellular Senescence; Cartilage, Articular
PubMed: 38494091
DOI: 10.1016/j.arr.2024.102275 -
Experimental Gerontology Aug 2023Ageing is a natural process with physiological changes in different body parts and has been associated with decreased reproductive capacity. Factors such as imbalance in... (Review)
Review
Ageing is a natural process with physiological changes in different body parts and has been associated with decreased reproductive capacity. Factors such as imbalance in the antioxidant defence system, vascular diseases, diabetes mellitus, accessory reproductive glands infection, obesity as well as buildup of toxic substances play a role in age-related male reproductive malfunction. Age is inversely proportional to volume of semen, sperm count, sperm progressive motility, sperm viability, normal sperm morphology. The observed negative correlation between ageing and semen indices contributes to male infertility and reproductive decline. Normal levels of ROS, plays crucial role in facilitating sperm function, such as capacitation, hyper-activation, acrosome reaction as well as sperm-oocyte fusion; however, a substantial elevation in the endogenous level of ROS, especially in reproductive tissues, usually instigates destruction of sperm cells and heightened male infertility. Contrarily, antioxidants, such as vitamins C and E, beta-carotene, and micronutrients like zinc and folate, have been found by researchers to facilitate normal semen quality and male reproductive function. Furthermore, the role of hormonal imbalance as a result of the compromised hypothalamic-pituitary-gonadal axis, Sertoli and Leydig cells disorder, and nitric oxide-medicated erectile dysfunction during ageing cannot be undermined.
Topics: Male; Humans; Semen Analysis; Semen; Reactive Oxygen Species; Spermatozoa; Antioxidants; Infertility, Male; Aging; Sperm Motility
PubMed: 37315721
DOI: 10.1016/j.exger.2023.112232 -
Age and Ageing May 2024
Topics: Humans; Healthy Aging; Nutritional Status; Aged; Aging; Diet, Healthy; Age Factors
PubMed: 38745487
DOI: 10.1093/ageing/afae053 -
Mechanisms of Ageing and Development Oct 2023Aging-related diseases are closely associated with the state of inflammation, which is known as "inflammaging." Senescent cells are metabolically active, as exemplified...
Aging-related diseases are closely associated with the state of inflammation, which is known as "inflammaging." Senescent cells are metabolically active, as exemplified by the secretion of inflammatory cytokines, chemokines, and growth factors, which is termed the senescence-associated secretory phenotype (SASP). Epigenetic regulation, especially the structural regulation of chromatin, is closely linked to the regulation of SASP. In our previous study, the suppressor of variegation 3-9 homolog 1 (SUV39H1) was elucidated to interact with Lhx8 and determine the cell fate of mesenchyme stem cells. However, the function of SUV39H1 during aging and the underlying mechanism of its epigenetic regulation remains controversial. Therefore, the C57BL/6 J CAG-Cre; SUV39H1 knockout mice and irradiation-induced cellular senescence model were built in this study to deepen the understanding of epigenetic regulation by SUV39H1 and its relation to SASP. In vivo and in vitro studies demonstrated that SUV39H1 decreased with aging and served as an inhibitor of SASP, especially IL-6, MCP-1, and Vcam-1, by altering H3K9me3 enrichment in their promoter region. These results provide new insights into the epigenetic regulation of SASP.
Topics: Animals; Mice; Aging; Cellular Senescence; Epigenesis, Genetic; Histone Methyltransferases; Histones; Mice, Inbred C57BL; Stem Cells; Senescence-Associated Secretory Phenotype
PubMed: 37666472
DOI: 10.1016/j.mad.2023.111868 -
The Lancet. Healthy Longevity Sep 2023
Topics: Sleep Duration; Cognitive Aging; Exercise; Cognition
PubMed: 37659426
DOI: 10.1016/S2666-7568(23)00137-X -
Aging Cell Sep 2023Lipid signaling is involved in longevity regulation, but which specific lipid molecular species affect human biological aging remains largely unknown. We investigated...
Lipid signaling is involved in longevity regulation, but which specific lipid molecular species affect human biological aging remains largely unknown. We investigated the relation between complex lipids and DNA methylation-based metrics of biological aging among 4181 participants (mean age 55.1 years (range 30.0-95.0)) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany. The absolute concentration of 14 lipid classes, covering 964 molecular species and 267 fatty acid composites, was measured by Metabolon Complex Lipid Panel. DNA methylation-based metrics of biological aging (AgeAccelPheno and AgeAccelGrim) were calculated based on published algorithms. Epigenome-wide association analyses (EWAS) of biological aging-associated lipids and pathway analysis were performed to gain biological insights into the mechanisms underlying the effects of lipidomics on biological aging. We found that higher levels of molecular species belonging to neutral lipids, phosphatidylethanolamines, phosphatidylinositols, and dihydroceramides were associated with faster biological aging, whereas higher levels of lysophosphatidylcholine, hexosylceramide, and lactosylceramide species were associated with slower biological aging. Ceramide, phosphatidylcholine, and lysophosphatidylethanolamine species with odd-numbered fatty acid tail lengths were associated with slower biological aging, whereas those with even-numbered chain lengths were associated with faster biological aging. EWAS combined with functional pathway analysis revealed several complex lipids associated with biological aging as important regulators of known longevity and aging-related pathways.
Topics: Adult; Humans; Middle Aged; Aged; Aged, 80 and over; Longevity; Lipidomics; Cohort Studies; Aging; DNA Methylation; Fatty Acids; Epigenesis, Genetic
PubMed: 37496173
DOI: 10.1111/acel.13934 -
Aging Cell Jan 2024Originally identified as an outcome of continuous culture of primary cells, cellular senescence has moved beyond the culture dish and is now a bona fide driver of aging... (Review)
Review
Originally identified as an outcome of continuous culture of primary cells, cellular senescence has moved beyond the culture dish and is now a bona fide driver of aging and disease in animal models, and growing links to human disease. This cellular stress response consists of a stable proliferative arrest coupled to multiple phenotypic changes. Perhaps the most important of these is the senescence-associated secretory phenotype, or senescence-associated secretory phenotype -a complex and variable collection of secreted molecules release by senescent cells with a number of potent biological activities. Senescent cells appear in multiple age-associated conditions in humans and mice, and interventions that eliminate these cells can prevent or even reverse multiple diseases in mouse models. Here, we review salient aspects of senescent cells in the context of human disease and homeostasis. Senescent cells increase in abundance during several diseases that associated with premature aging. Conversely, senescent cells have a key role in beneficial processes such as development and wound healing, and thus can help maintain tissue homeostasis. Finally, we speculate on mechanisms by which deleterious aspects of senescent cells might be targeted while retaining homeostatic aspects in order to improve age-related outcomes.
Topics: Humans; Animals; Mice; Aging; Cellular Senescence; Disease Models, Animal; Senescence-Associated Secretory Phenotype; Homeostasis
PubMed: 37731189
DOI: 10.1111/acel.13988 -
Ageing Research Reviews Jun 2024Ovarian aging is marked by a reduction in the quantity and quality of ovarian follicles, leading to a decline in female fertility and ovarian endocrine function. While... (Review)
Review
Ovarian aging is marked by a reduction in the quantity and quality of ovarian follicles, leading to a decline in female fertility and ovarian endocrine function. While the biological characteristics of ovarian aging are well-established, the exact mechanisms underlying this process remain elusive. Recent studies underscore the vital role of trace elements (TEs) in maintaining ovarian function. Imbalances in TEs can lead to ovarian aging, characterized by reduced enzyme activity, hormonal imbalances, ovulatory disorders, and decreased fertility. A comprehensive understanding of the relationship between systemic and cellular TEs balance and ovarian aging is critical for developing treatments to delay aging and manage age-related conditions. This review consolidates current insights into TEs homeostasis and its impact on ovarian aging, assesses how altered TEs metabolism affects ovarian aging, and suggests future research directions to prolong ovarian reproductive life. These studies are expected to offer novel approaches for mitigating ovarian aging.
Topics: Female; Humans; Homeostasis; Ovary; Trace Elements; Aging; Animals; Reproduction
PubMed: 38636559
DOI: 10.1016/j.arr.2024.102311 -
The EMBO Journal Aug 2023Mitochondria are central regulators of healthspan and lifespan, yet the intricate choreography of multiple, tightly controlled steps regulating mitochondrial biogenesis...
Mitochondria are central regulators of healthspan and lifespan, yet the intricate choreography of multiple, tightly controlled steps regulating mitochondrial biogenesis remains poorly understood. Here, we uncover a pivotal role for specific elements of the 5'-3' mRNA degradation pathway in the regulation of mitochondrial abundance and function. We find that the mRNA degradation and the poly-A tail deadenylase CCR4-NOT complexes form distinct foci in somatic Caenorhabditis elegans cells that physically and functionally associate with mitochondria. Components of these two multi-subunit complexes bind transcripts of nuclear-encoded mitochondria-targeted proteins to regulate mitochondrial biogenesis during ageing in an opposite manner. In addition, we show that balanced degradation and storage of mitochondria-targeted protein mRNAs are critical for mitochondrial homeostasis, stress resistance and longevity. Our findings reveal a multifaceted role of mRNA metabolism in mitochondrial biogenesis and show that fine-tuning of mRNA turnover and local translation control mitochondrial abundance and promote longevity in response to stress and during ageing.
Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Aging; Mitochondria; Longevity
PubMed: 37427543
DOI: 10.15252/embj.2022112446 -
Nature Genetics Feb 2024Understanding why we age is a long-standing question, and many mechanistic theories of aging have been proposed. Owing to limitations in studying the aging process,... (Review)
Review
Understanding why we age is a long-standing question, and many mechanistic theories of aging have been proposed. Owing to limitations in studying the aging process, including a lack of adequate quantitative measurements, its mechanistic basis remains a subject of debate. Here, I explore theories of aging from the perspective of causal relationships. Many aging-related changes have been observed and touted as drivers of aging, including molecular changes in the genome, telomeres, mitochondria, epigenome and proteins and cellular changes affecting stem cells, the immune system and senescent cell buildup. Determining which changes are drivers and not passengers of aging remains a challenge, however, and I discuss how animal models and human genetic studies have been used empirically to infer causality. Overall, our understanding of the drivers of human aging is still inadequate; yet with a global aging population, elucidating the causes of aging has the potential to revolutionize biomedical research.
Topics: Animals; Humans; Aged; Aging; Biomedical Research; Models, Animal; Proteins
PubMed: 38242993
DOI: 10.1038/s41588-023-01627-0