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Ageing Research Reviews Nov 2023Gene expression is tremendously altered in the brain during memory acquisition, recall, and forgetfulness. However, non-genetic factors, including environmental... (Review)
Review
Gene expression is tremendously altered in the brain during memory acquisition, recall, and forgetfulness. However, non-genetic factors, including environmental elements, epigenetic changes, and lifestyle, have grabbed significant attention in recent years regarding the etiology of neurodegenerative diseases (NDD) and age-associated dementia. Epigenetic modifications are essential in regulating gene expression in all living organisms in a DNA sequence-independent manner. The genes implicated in ageing and NDD-related memory disorders are epigenetically regulated by processes such as DNA methylation, histone acetylation as well as messenger RNA editing machinery. The physiological and optimal state of the epigenome, especially within the CNS of humans, plays an intricate role in helping us adjust to the changing environment, and alterations in it cause many brain disorders, but the mechanisms behind it still need to be well understood. When fully understood, these epigenetic landscapes could act as vital targets for pharmacogenetic rescue strategies for treating several diseases, including neurodegeneration- and age-induced dementia. Keeping this objective in mind, this updated review summarises the epigenetic changes associated with age and neurodegeneration-associated dementia.
Topics: Humans; Epigenesis, Genetic; DNA Methylation; Brain Diseases; Neurodegenerative Diseases; Aging; Memory Disorders; Dementia
PubMed: 37689143
DOI: 10.1016/j.arr.2023.102067 -
Journal of Cellular and Molecular... Sep 2023We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular... (Review)
Review
We are facing a growing aging population, along with increasing pressure on health systems, caused by the impact of chronic co-morbidities (i.e. cancer, cardiovascular and neurodegenerative diseases) and functional disabilities as people age. Relatively simple preventive lifestyle interventions, such as dietary restriction and physical exercise, are important contributors to active and healthy aging in the general population. However, as shown in model organisms or in 'in vitro' conditions, lifestyle-independent interventions may have additional health benefits and can even be conceived as possible reversers of the aging process. Thus, pharmaceutical laboratories, research institutes, and universities are putting more and more effort into finding new molecular pathways and druggable targets to develop gerotherapeutics. One approach is to target the driving mechanisms of aging, some of which, like cellular senescence and impaired autophagy, we discussed in an update on the biology of aging at AgingFit 2023 in Lille, France. We underline the importance of carefully and extensively testing senotherapeutics, given the pleiotropism and heterogeneity of targeted senescent cells within different organs, at different time frames. Other druggable targets emerging from new putative mechanisms, like those based on transcriptome imbalance, nucleophagy, protein phosphatase depletion, glutamine metabolism, or seno-antigenicity, have been evidenced by recent preclinical studies in classical models of aging but need to be validated in humans. Finally, we highlight several approaches in the discovery of biomarkers of healthy aging, as well as for the prediction of neurodegenerative diseases and the evaluation of rejuvenation strategies.
Topics: Humans; Aged; Longevity; Aging; Medicine; Biomedical Research; Cellular Senescence
PubMed: 37610311
DOI: 10.1111/jcmm.17912 -
Methods in Cell Biology 2024
Topics: Humans; Aging; Cellular Senescence; Neoplasms
PubMed: 38302247
DOI: 10.1016/S0091-679X(24)00009-8 -
Mechanisms of Ageing and Development Oct 2023Inflammaging is a low-grade inflammatory state that can be considered an adaptive process aimed at stimulating appropriate anti-inflammatory response. Frailty is...
Inflammaging is a low-grade inflammatory state that can be considered an adaptive process aimed at stimulating appropriate anti-inflammatory response. Frailty is determined by the accumulation of molecular and cellular defects accumulated throughout life; therefore, an appropriate frailty computation could be a valuable tool for measuring biological age. This study aims to analyse the association between inflammatory markers and both chronological age "per se" and frailty. We studied 452 persons aged 43-114 years. A Frailty Index (FI) was computed considering a wide range of age-related signs, symptoms, disabilities, and diseases. Plasma concentrations of inflammatory cytokines and peripheral markers of neuroinflammation were analysed by next-generation ELISA. The mean age of the cohort was 79.7 (from 43 to 114) years and the median FI was 0.19 (from 0.00 to 0.75). The concentrations of most inflammatory markers increased significantly with chronological age, after adjustment for sex and FI. Interferon-γ was significantly affected only by FI, while interleukin (IL)-10 and IL-1β were associated only with chronological age. In conclusion, we described different associations between inflammatory components and chronological vs. biological age. A better characterization of the molecular signature of aging could help to understand the complexity of this process.
Topics: Humans; Aged; Aged, 80 and over; Frailty; Aging; Inflammation; Cytokines
PubMed: 37689318
DOI: 10.1016/j.mad.2023.111872 -
Ageing Research Reviews Jul 2023While aging was traditionally viewed as a stochastic process of damage accumulation, it is now clear that aging is strongly influenced by genetics. The identification... (Review)
Review
While aging was traditionally viewed as a stochastic process of damage accumulation, it is now clear that aging is strongly influenced by genetics. The identification and characterization of long-lived genetic mutants in model organisms has provided insights into the genetic pathways and molecular mechanisms involved in extending longevity. Long-lived genetic mutants exhibit activation of multiple stress response pathways leading to enhanced resistance to exogenous stressors. As a result, lifespan exhibits a significant, positive correlation with resistance to stress. Disruption of stress response pathways inhibits lifespan extension in multiple long-lived mutants representing different pathways of lifespan extension and can also reduce the lifespan of wild-type animals. Combined, this suggests that activation of stress response pathways is a key mechanism by which long-lived mutants achieve their extended longevity and that many of these pathways are also required for normal lifespan. These results highlight an important role for stress response pathways in determining the lifespan of an organism.
Topics: Animals; Humans; Longevity; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Aging; Oxidative Stress
PubMed: 37127095
DOI: 10.1016/j.arr.2023.101941 -
Ageing Research Reviews Apr 2024In recent years, intermittent fasting (IF) and its numerous modifications have been increasingly suggested as a promising therapy for age-related problems and a... (Review)
Review
In recent years, intermittent fasting (IF) and its numerous modifications have been increasingly suggested as a promising therapy for age-related problems and a non-pharmacological strategy to extend lifespan. Despite the great variability in feeding schedules that we describe in the current work, underlying physiological processes are the same and include a periodic switch from glucose metabolism (generated by glycogenolysis) to fatty acids and fatty acid-derived ketones. Many of the beneficial effects of IF appear to be mediated by optimization of energy utilization. Findings to date from both human and animal experiments indicate that fasting improves physiological function, enhances performance, and slows aging and disease processes. In this review, we discuss some of the remarkable discoveries about the beneficial effects of IF on metabolism, endocrine and cardiovascular systems, cancer prevention, brain health, neurodegeneration and aging. Experimental studies on rodent models and human investigations are summarized to compare the outcomes and underlying mechanisms of IF. Metabolic and cellular responses triggered by IF could help to achieve the aim of preventing disease, and maximizing healthspan and longevity with minimal side effects.
Topics: Animals; Humans; Longevity; Intermittent Fasting; Fasting; Aging; Models, Animal; Fatty Acids
PubMed: 38499159
DOI: 10.1016/j.arr.2024.102274 -
Ageing Research Reviews Mar 2024The human female reproductive lifespan significantly diminishes with age, leading to decreased fertility, reduced fertility quality and endocrine function disorders.... (Review)
Review
The human female reproductive lifespan significantly diminishes with age, leading to decreased fertility, reduced fertility quality and endocrine function disorders. While many aspects of aging in general have been extensively documented, the precise mechanisms governing programmed aging in the female reproductive system remain elusive. Recent advancements in omics technologies and computational capabilities have facilitated the emergence of multiomics deep phenotyping. Through the application and refinement of various high-throughput omics methods, a substantial volume of omics data has been generated, deepening our comprehension of the pathogenesis and molecular underpinnings of reproductive aging. This review highlights current and emerging multiomics approaches for investigating female reproductive aging, encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics. We elucidate their influence on fundamental cell biology and translational research in the context of reproductive aging, address the limitations and current challenges associated with multiomics studies, and offer a glimpse into future prospects.
Topics: Female; Humans; Multiomics; Genomics; Proteomics; Reproduction; Aging
PubMed: 38401570
DOI: 10.1016/j.arr.2024.102245 -
Mechanisms of Ageing and Development Oct 2023Iron is the most abundant trace element in the human body. Since iron can switch between its 2-valent and 3-valent form it is essential in various physiological... (Review)
Review
Iron is the most abundant trace element in the human body. Since iron can switch between its 2-valent and 3-valent form it is essential in various physiological processes such as energy production, proliferation or DNA synthesis. Especially high metabolic organs such as the heart rely on iron-associated iron-sulfur and heme proteins. However, due to switches in iron oxidation state, iron overload exhibits high toxicity through formation of reactive oxygen species, underlining the importance of balanced iron levels. Growing evidence demonstrates disturbance of this balance during aging. While age-associated cardiovascular diseases are often related to iron deficiency, in physiological aging cardiac iron accumulates. To understand these changes, we focused on inflammation and proteolysis, two hallmarks of aging, and their role in iron metabolism. Via the IL-6-hepcidin axis, inflammation and iron status are strongly connected often resulting in anemia accompanied by infiltration of macrophages. This tight connection between anemia and inflammation highlights the importance of the macrophage iron metabolism during inflammation. Age-related decrease in proteolytic activity additionally affects iron balance due to impaired degradation of iron metabolism proteins. Therefore, this review accentuates alterations in iron metabolism during aging with regards to inflammation and proteolysis to draw attention to their implications and associations.
Topics: Humans; Iron; Proteolysis; Anemia; Inflammation; Aging
PubMed: 37678569
DOI: 10.1016/j.mad.2023.111869 -
Chemical Research in Toxicology Dec 2023Proper maintenance of genomic DNA is upheld by tight control of cellular metabolism and DNA processing. Herein, we review recent advances in examining the role of... (Review)
Review
Proper maintenance of genomic DNA is upheld by tight control of cellular metabolism and DNA processing. Herein, we review recent advances in examining the role of endogenous metabolites and genomic instability in aging and disease as presented at the Fall 2023 American Chemical Society Meeting.
Topics: Humans; Aging; Genomic Instability; DNA Damage; DNA Repair; DNA
PubMed: 37947799
DOI: 10.1021/acs.chemrestox.3c00288 -
Journal of Integrative Neuroscience Jan 2024Both classic epigenetic modifications and microRNAs can impact a range of bodily processes, from metabolism to brain function, and may contribute to the development of... (Review)
Review
Both classic epigenetic modifications and microRNAs can impact a range of bodily processes, from metabolism to brain function, and may contribute to the development of diseases such as cancer, cardiovascular disorders, and psychiatric disorders. Numerous studies suggest a connection between epigenetic changes and mood disorders. In this study, we performed a comprehensive search using PubMed and Google for the terms "epigenetics", "ageing", "miRNA", "schizophrenia", and "mood disorders" in the titles and abstracts of articles. Epigenetic changes during early life may play a crucial role in triggering severe mental disorders and shaping their clinical trajectory. Although these alterations can take place at any age, their impact may not be immediately evident or observable until later in life. Epigenetic modifications play a crucial role in the ageing process and challenge the prevailing belief that mutations are the primary driver of ageing. However, it is plausible that these epigenetic changes are a consequence of the disorder rather than its root cause. Moreover, both the disorder and the epigenetic alterations may be influenced by shared environmental or genetic factors. In the near future, we might be able to replace chronological age with biological age, based on the epigenetic clock, with the promise of providing greater therapeutic benefits. A wide range of epigenetic drugs are currently under development at various stages. Although their full effectiveness is yet to be realized, they show great potential in the treatment of cancer, psychiatric disorders, and other complex diseases.
Topics: Humans; DNA Methylation; Epigenesis, Genetic; Mental Disorders; Schizophrenia; MicroRNAs; Aging
PubMed: 38287856
DOI: 10.31083/j.jin2301013