bims-longev Biomed News
on Longevity
Issue of 2023–01–08
seventeen papers selected by
Andreea Nitescu
  1. Meta-hallmarks of aging and cancer.
  2. Hallmarks of aging: An expanding universe.
  3. Cellular Senescence and Ageing.
  4. The Proteasome and Ageing.
  5. Autophagy and longevity: Evolutionary hints from hyper-longevous mammals.
  6. Early Life Reprogramming-Based Treatment Promotes Longevity.
  7. Gap Junctions and Ageing.
  8. Mitochondria in Aging and Alzheimer's Disease: Focus on Mitophagy.
  9. Epigenetic alterations-The silent indicator for early aging and age-associated health-risks.
  10. Anti-aging effects of dietary phytochemicals: From Caenorhabditis elegans, Drosophila melanogaster, rodents to clinical studies.
  11. Neuroprotective effects of onion and garlic root extracts against Alzheimer's disease in rats: antimicrobial, histopathological, and molecular studies.
  12. Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics.
  13. Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort.
  14. Extracellular Vesicles and Cellular Ageing.
  15. CircRNA and Ageing.
  16. Immune system modulation in aging: Molecular mechanisms and therapeutic targets.
  17. Effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, with a focus on atherosclerosis.
  1. Cell Metab. 2023 Jan 03. pii: S1550-4131(22)00492-2. [Epub ahead of print]35(1): 12-35
    Meta-hallmarks of aging and cancer.
    Carlos López-Otín, Federico Pietrocola, David Roiz-Valle, Lorenzo Galluzzi, Guido Kroemer.
      Both aging and cancer are characterized by a series of partially overlapping "hallmarks" that we subject here to a meta-analysis. Several hallmarks of aging (i.e., genomic instability, epigenetic alterations, chronic inflammation, and dysbiosis) are very similar to specific cancer hallmarks and hence constitute common "meta-hallmarks," while other features of aging (i.e., telomere attrition and stem cell exhaustion) act likely to suppress oncogenesis and hence can be viewed as preponderantly "antagonistic hallmarks." Disabled macroautophagy and cellular senescence are two hallmarks of aging that exert context-dependent oncosuppressive and pro-tumorigenic effects. Similarly, the equivalence or antagonism between aging-associated deregulated nutrient-sensing and cancer-relevant alterations of cellular metabolism is complex. The agonistic and antagonistic relationship between the processes that drive aging and cancer has bearings for the age-related increase and oldest age-related decrease of cancer morbidity and mortality, as well as for the therapeutic management of malignant disease in the elderly.
    Keywords:  aging; cancer; carcinogenesis; metabolism; oncogenesis; tumor progression
    DOI:  https://doi.org/10.1016/j.cmet.2022.11.001
  2. Cell. 2022 Dec 26. pii: S0092-8674(22)01377-0. [Epub ahead of print]
    Hallmarks of aging: An expanding universe.
    Carlos López-Otín, Maria A Blasco, Linda Partridge, Manuel Serrano, Guido Kroemer.
      Aging is driven by hallmarks fulfilling the following three premises: (1) their age-associated manifestation, (2) the acceleration of aging by experimentally accentuating them, and (3) the opportunity to decelerate, stop, or reverse aging by therapeutic interventions on them. We propose the following twelve hallmarks of aging: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, disabled macroautophagy, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, chronic inflammation, and dysbiosis. These hallmarks are interconnected among each other, as well as to the recently proposed hallmarks of health, which include organizational features of spatial compartmentalization, maintenance of homeostasis, and adequate responses to stress.
    DOI:  https://doi.org/10.1016/j.cell.2022.11.001
  3. Subcell Biochem. 2023 ;102 139-173
    Cellular Senescence and Ageing.
    Rebecca Reed, Satomi Miwa.
      Cellular senescence has become a subject of great interest within the ageing research field over the last 60 years, from the first observation in vitro by Leonard Hayflick and Paul Moorhead in 1961, to novel findings of phenotypic sub-types and senescence-like phenotype in post-mitotic cells. It has essential roles in wound healing, tumour suppression and the very first stages of human development, while causing widespread damage and dysfunction with age leading to a raft of age-related diseases. This chapter discusses these roles and their interlinking pathways, and how the observed accumulation of senescent cells with age has initiated a whole new field of ageing research, covering pathologies in the heart, liver, kidneys, muscles, brain and bone. This chapter will also examine how senescent cell accumulation presents in these different tissues, along with their roles in disease development. Finally, there is much focus on developing treatments for senescent cell accumulation in advanced age as a method of alleviating age-related disease. We will discuss here the various senolytic and senostatic treatment approaches and their successes and limitations, and the innovative new strategies being developed to address the differing effects of cellular senescence in ageing and disease.
    Keywords:  Age-related disease; Ageing; SA-β-Gal; SASP; Senescence; Senolytic; Senostatic; Telomeres
    DOI:  https://doi.org/10.1007/978-3-031-21410-3_7
  4. Subcell Biochem. 2023 ;102 99-112
    The Proteasome and Ageing.
    Ashok N Hegde, Lindsey M Duke, Logan E Timm, Hannah Nobles.
      The proteasome is a multi-subunit proteolytic complex that functions to degrade normal proteins for physiological regulation and to eliminate abnormal proteins for cellular protection. Generally, the proteasome targets substrate proteins that are marked by attachment of multiple ubiquitin molecules. In various types of cells in an organism, damage to proteins occurs both from internal sources such as reactive oxygen species and from external ones such as UV radiation from the sun. The proteasome functions to protect the cells by degrading damaged proteins. With ageing, however, the capacity of the proteasome to degrade damaged proteins is reduced as indicated by evidence gathered by many studies. Studies on ageing in muscle, skin, and brain show that with age catalytic activity of the proteasome is decreased and the expression of proteasome subunits is altered. Age-related accumulation of damaged or misfolded proteins causes further reduction of proteasome activity. Abnormal proteins also accumulate as a result of age-related neurodegenerative diseases. Deficits in proteasome activity might be responsible for accumulation of protein aggregates and thus contribute to the pathology. Results from several studies suggest a link between the proteasome and longevity. This chapter reviews the various ways in which the proteasome is associated with the ageing process and examines evidence gathered from investigations on cultured cells, model organisms, and humans.
    Keywords:  Longevity; Misfolded proteins; Neurodegeneration; Oxidative damage; Protein degradation; Proteolysis; Proteostasis; Senescence; Ubiquitin
    DOI:  https://doi.org/10.1007/978-3-031-21410-3_5
  5. Front Endocrinol (Lausanne). 2022 ;13 1085522
    Autophagy and longevity: Evolutionary hints from hyper-longevous mammals.
    Andrea G Locatelli, Simone Cenci.
      Autophagy is a fundamental multi-tasking adaptive cellular degradation and recycling strategy. Following its causal implication in age-related decline, autophagy is currently among the most broadly studied and challenged mechanisms within aging research. Thanks to these efforts, new cellular nodes interconnected with this phylogenetically ancestral pathway and unexpected roles of autophagy-associated genetic products are unveiled daily, yet the history of functional adaptations of autophagy along its evolutive trail is poorly understood and documented. Autophagy is traditionally studied in canonical and research-wise convenient model organisms such as yeast and mice. However, unconventional animal models endowed with extended longevity and exemption from age-related diseases offer a privileged perspective to inquire into the role of autophagy in the evolution of longevity. In this mini review we retrace the appearance and functions evolved by autophagy in eukaryotic cells and its protective contribution in the pathophysiology of aging.
    Keywords:   aging; ATG; age-related diseases; autophagy; bats; evolution; longevity; mitochondria
    DOI:  https://doi.org/10.3389/fendo.2022.1085522
  6. Cell Reprogram. 2022 Dec 30.
    Early Life Reprogramming-Based Treatment Promotes Longevity.
    Patrizia Pessina, Bruno Di Stefano.
      Short-term expression of Yamanaka factors early in life promotes epigenetic reprogramming and an increased healthy lifespan in a mouse model of accelerated aging.
    Keywords:  aging; epigenetic clock; rejuvenation; reprogramming
    DOI:  https://doi.org/10.1089/cell.2022.0153
  7. Subcell Biochem. 2023 ;102 113-137
    Gap Junctions and Ageing.
    Michael J Zeitz, James W Smyth.
      Gap junctions, comprising connexin proteins, create conduits directly coupling the cytoplasms of adjacent cells. Expressed in essentially all tissues, dynamic gap junction structures enable the exchange of small molecules including ions and second messengers, and are central to maintenance of homeostasis and synchronized excitability. With such diverse and critical roles throughout the body, it is unsurprising that alterations to gap junction and/or connexin expression and function underlie a broad array of age-related pathologies. From neurological dysfunction to cardiac arrhythmia and bone loss, it is hard to identify a human disease state that does not involve reduced, or in some cases inappropriate, intercellular communication to affect organ function. With a complex life cycle encompassing several key regulatory steps, pathological gap junction remodeling during ageing can arise from alterations in gene expression, translation, intracellular trafficking, and posttranslational modification of connexins. Connexin proteins are now known to "moonlight" and perform a variety of non-junctional functions in the cell, independent of gap junctions. Furthermore, connexin "hemichannels" on the cell surface can communicate with the extracellular space without ever coupling to an adjacent cell to form a gap junction channel. This chapter will focus primarily on gap junctions in ageing, but such non-junctional connexin functions will be referred to where appropriate and the full spectrum of connexin biology should be noted as potentially causative/contributing to some findings in connexin knockout animals, for example.
    Keywords:  Ageing; Connexin; Gap junction; Homeostasis; Intercellular communication
    DOI:  https://doi.org/10.1007/978-3-031-21410-3_6
  8. Neuroscientist. 2023 Jan 03. 10738584221139761
    Mitochondria in Aging and Alzheimer's Disease: Focus on Mitophagy.
    Jangampalli Adi Pradeepkiran, Javaria Baig, Ashley Selman, P Hemachandra Reddy.
      Alzheimer's disease (AD) is characterized by the accumulation of amyloid β and phosphorylated τ protein aggregates in the brain, which leads to the loss of neurons. Under the microscope, the function of mitochondria is uniquely primed to play a pivotal role in neuronal cell survival, energy metabolism, and cell death. Research studies indicate that mitochondrial dysfunction, excessive oxidative damage, and defective mitophagy in neurons are early indicators of AD. This review article summarizes the latest development of mitochondria in AD: 1) disease mechanism pathways, 2) the importance of mitochondria in neuronal functions, 3) metabolic pathways and functions, 4) the link between mitochondrial dysfunction and mitophagy mechanisms in AD, and 5) the development of potential mitochondrial-targeted therapeutics and interventions to treat patients with AD.
    Keywords:  Alzheimer disease; adenosine triphosphate; amyloid beta; amyloid precursor protein; dysfunction; mitochondria; mitophagy; neurofibrillary tangle; p-tau; reaction oxidative stress; therapeutics
    DOI:  https://doi.org/10.1177/10738584221139761
  9. Aging Med (Milton). 2022 Dec;5(4): 287-293
    Epigenetic alterations-The silent indicator for early aging and age-associated health-risks.
    Poulami Dhar, Shailaja S Moodithaya, Prakash Patil.
      Aging is the process of gradual physiological deterioration till death and this process perpetually reduce the functionality of an individual. To address the rationale and provide geriatric care, the constant target of geroscience is to identify reliable biomarkers for aging. Over the past decades, diversified advancements in epigenetic studies crescively support the fact that the accumulation of epigenetic changes accompanies the process of aging. A growing number of studies have suggested that alterations occur through three fundamental mechanisms like methylation of DNA, histone protein modification, and production of non-coding microRNAs. Each of these changes occurs silently and provokes alterations in the circumstantial expression of genetic material without altering the underlying gene sequences. The changes in gene expression due to epigenetic alterations are suggested to be the cause of early aging and the onset of age-related health risks. This review would attempt to give an integrated overview of epigenetic changes related to aging and age-associated health risks. This review also discussed epigenomes influencing early aging and factors modulating it. Since epigenetic changes are reversible, early identification of epigenetic markers can be a hope for future geriatric medicine. Finally, this review emphasizes the identification of blood-based epigenetic biomarkers in order to enlighten the future scope for therapeutic intervention to slow down the aging process.
    Keywords:  DNA‐methylation; MiRNA; aging; epigenetics; histone‐modification
    DOI:  https://doi.org/10.1002/agm2.12236
  10. Crit Rev Food Sci Nutr. 2023 Jan 03. 1-26
    Anti-aging effects of dietary phytochemicals: From Caenorhabditis elegans, Drosophila melanogaster, rodents to clinical studies.
    Ju-Chi Chen, Reuben Wang, Chia-Cheng Wei.
      Anti-aging research has become critical since the elderly population is increasing dramatically in this era. With the establishment of frailty phenotype and frailty index, the importance of anti-frailty research is concurrently enlightened. The application of natural phytochemicals against aging or frailty is always intriguing, and abundant related studies have been published. Various models are designed for biological research, and each model has its strength and weakness in deciphering the complex aging mechanisms. In this article, we attempt to show the potential of Caenorhabditis elegans in the study of phytochemicals' effects on anti-aging by comparing it to other animal models. In this review, the lifespan extension and anti-aging effects are demonstrated by various physical, cellular, or molecular biomarkers of dietary phytochemicals, including resveratrol, curcumin, urolithin A, sesamin, fisetin, quercetin, epigallocatechin-3-gallate, epicatechin, spermidine, sulforaphane, along with extracts of broccoli, cocoa, and blueberry. Meanwhile, the frequency of phytochemicals and models studied or presented in publications since 2010 were analyzed, and the most commonly mentioned animal models were rats, mice, and the nematode C. elegans. This up-to-date summary of the anti-aging effect of certain phytochemicals has demonstrated powerful potential for anti-aging or anti-frailty in the human population.
    Keywords:  Aging; animal model; frailty; lifespan extension; phytochemicals; sarcopenia
    DOI:  https://doi.org/10.1080/10408398.2022.2160961
  11. BioTechnologia (Pozn). 2022 ;103(2): 153-167
    Neuroprotective effects of onion and garlic root extracts against Alzheimer's disease in rats: antimicrobial, histopathological, and molecular studies.
    Eman M Hegazy, Ayman Sabry, Wagdy K B Khalil.
      Alzheimer's disease (AD) is a brain disorder and the main reason for dementia. In this regard, there is a need to understand the alterations that occur during aging to develop treatment strategies to mitigate or prevent neurodegenerative consequences. Onion and garlic root extracts contain natural polyphenols with high antioxidant capacity; therefore, the present study aimed to investigate the protective effect of these extracts free from mycotoxin contamination on a rat model of AD. Antifungal and antibacterial assays were performed for onion and garlic extracts. Several groups of AD-induced rats were administered 1, 2, and 3 mg/kg onion or garlic extract through intragastric intubation for 30 days. After treatment, histopathological analysis, expression of apoptosis-related genes, and analyses of DNA damage and reactive oxygen species (ROS) generation were conducted in the brain tissues. The results indicate that treatment of AD-induced rats with several doses of onion and garlic root extracts decreased histopathological lesions, the expression levels of apoptotic genes, and the rate of DNA damage and inhibited intracellular ROS generation in the brain tissues. The results suggest that the protective role of onion root extract could be attributed to its content of flavonoids and flavonoid compounds through the improvement of antioxidant capacity and regulation of gene expression patterns. The higher activity levels of free radical scavenging of azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) and antioxidant ferric reducing antioxidant power (FRAP) levels found in garlic root extract are most probably responsible for its protective effect against neurodegenerative damage.
    Keywords:  Alzheimer; antimicrobial; comet; garlic; gene expression; histology; mycotoxins; onion
    DOI:  https://doi.org/10.5114/bta.2022.116210
  12. Exp Mol Med. 2023 Jan 04.
    Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics.
    Yeaeun Han, Sung Young Kim.
      Senescence compromises the essential role that the endothelium plays in maintaining vascular homeostasis, so promoting endothelial dysfunction and the development of age-related vascular diseases. Their biological and clinical significance calls for strategies for identifying and therapeutically targeting senescent endothelial cells. While senescence and endothelial dysfunction have been studied extensively, distinguishing what is distinctly endothelial senescence remains a barrier to overcome for an effective approach to addressing it. Here, we review the mechanisms underlying endothelial senescence and the evidence for its clinical importance. Furthermore, we discuss the current state and the limitations in the approaches for the detection and therapeutic intervention of target cells, suggesting potential directions for future research.
    DOI:  https://doi.org/10.1038/s12276-022-00906-w
  13. Front Immunol. 2022 ;13 1065739
    Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort.
    Zhengtao Lv, Jiarui Cui, Jiaming Zhang.
       Objective: Hyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers.
    Methods: A Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-α, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis.
    Results: An inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; β=-0.040; SE=0.0072; P=4.37×10-8). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-α, or IGF-1 levels.
    Conclusions: Serum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.
    Keywords:  Mendelian randomization; aging; causal effect; serum urate; telomere length
    DOI:  https://doi.org/10.3389/fimmu.2022.1065739
  14. Subcell Biochem. 2023 ;102 271-311
    Extracellular Vesicles and Cellular Ageing.
    Nekane Romero-García, Cristina Mas-Bargues, Javier Huete-Acevedo, Consuelo Borrás.
      Ageing is a complex process characterized by deteriorated performance at multiple levels, starting from cellular dysfunction to organ degeneration. Stem cell-based therapies aim to administrate stem cells that eventually migrate to the injured site to replenish the damaged tissue and recover tissue functionality. Stem cells can be easily obtained and cultured in vitro, and display several qualities such as self-renewal, differentiation, and immunomodulation that make them suitable candidates for stem cell-based therapies. Current animal studies and clinical trials are being performed to assess the safety and beneficial effects of stem cell engraftments for regenerative medicine in ageing and age-related diseases.Since alterations in cell-cell communication have been associated with the development of pathophysiological processes, new research is focusing on the modulation of the microenvironment. Recent research has highlighted the important role of some microenvironment components that modulate cell-cell communication, thus spreading signals from damaged ageing cells to neighbor healthy cells, thereby promoting systemic ageing. Extracellular vesicles (EVs) are small-rounded vesicles released by almost every cell type. EVs cargo includes several bioactive molecules, such as lipids, proteins, and genetic material. Once internalized by target cells, their specific cargo can induce epigenetic modifications and alter the fate of the recipient cells. Also, EV's content is dependent on the releasing cells, thus, EVs can be used as biomarkers for several diseases. Moreover, EVs have been proposed to be used as cell-free therapies that focus on their administration to slow or even reverse some hallmarks of physiological ageing. It is not surprising that EVs are also under study as next-generation therapies for age-related diseases.
    Keywords:  Age-related diseases; Ageing; Extracellular vesicles; Intercellular communication; Regenerative medicine; Stem cells
    DOI:  https://doi.org/10.1007/978-3-031-21410-3_11
  15. Subcell Biochem. 2023 ;102 249-270
    CircRNA and Ageing.
    Ebrahim Mahmoudi, Murray J Cairns.
      Circular RNAs (circRNAs) are closed-loop RNA transcripts formed by a noncanonical back splicing mechanism. circRNAs are expressed in various tissues and cell types in a temporospatially regulated manner and have diverse molecular functions including their ability to act as miRNA sponges, transcriptional and splicing regulators, protein traps, and even templates for polypeptide synthesis. Emerging evidence suggests that circRNAs are themselves dynamically regulated throughout development in various organisms, with a substantial accumulation during ageing. Their regulatory roles in cellular pathways associated with ageing and senescence, as well as their implications in ageing-related diseases, such as neurological disease, cancer, and cardiovascular disease, suggest that circRNAs are key molecular determinants of the ageing process. Their unique structure, expression specificity, and biological functions highlight a potential capacity for use as novel biomarkers for diagnosis, prognosis, and treatment outcomes in a variety of conditions including pathological ageing. CircRNA may also have potential as target for interventions that manipulate ageing and longevity. In this chapter, we discuss the most recent advances in circRNA changes in ageing and ageing-associated disease.
    Keywords:  Ageing; Gene regulation; Transcription; Translation; ceRNA networks; circRNA; miRNA
    DOI:  https://doi.org/10.1007/978-3-031-21410-3_10
  16. Front Immunol. 2022 ;13 1059173
    Immune system modulation in aging: Molecular mechanisms and therapeutic targets.
    Bulmaro Cisneros, Ian García-Aguirre, Juan Unzueta, Isabel Arrieta-Cruz, Oscar González-Morales, Juan M Domínguez-Larrieta, Aura Tamez-González, Gerardo Leyva-Gómez, Jonathan J Magaña.
      The function of the immune system declines during aging, compromising its response against pathogens, a phenomenon termed as "immunosenescence." Alterations of the immune system undergone by aged individuals include thymic involution, defective memory T cells, impaired activation of naïve T cells, and weak memory response. Age-linked alterations of the innate immunity comprise perturbed chemotactic, phagocytic, and natural killing functions, as well as impaired antigen presentation. Overall, these alterations result in chronic low-grade inflammation (inflammaging) that negatively impacts health of elderly people. In this review, we address the most relevant molecules and mechanisms that regulate the relationship between immunosenescence and inflammaging and provide an updated description of the therapeutic strategies aimed to improve immunity in aged individuals.
    Keywords:  aging; chronic infections; immune system; immunosenescence; inflammaging
    DOI:  https://doi.org/10.3389/fimmu.2022.1059173
  17. Front Endocrinol (Lausanne). 2022 ;13 992937
    Effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, with a focus on atherosclerosis.
    Liu Yang, Xuejiao Zhang, Qing Wang.
      Atherosclerosis is a lipid-driven chronic inflammatory disease that is widespread in the walls of large and medium-sized arteries. Its pathogenesis is not fully understood. The currently known pathogenesis includes activation of pro-inflammatory signaling pathways in the body, increased oxidative stress, and increased expression of cytokines/chemokines. In the innate immune response, inflammatory vesicles are an important component with the ability to promote the expression and maturation of inflammatory factors, release large amounts of inflammatory cytokines, trigger a cascade of inflammatory responses, and clear pathogens and damaged cells. Studies in the last few years have demonstrated that NLRP3 inflammatory vesicles play a crucial role in the development of atherosclerosis as well as its complications. Several studies have shown that NLRP3 binding to ligands promotes inflammasome formation, activates caspase-1, and ultimately promotes its maturation and the maturation and production of IL-1β and IL-18. IL-1β and IL-18 are considered to be the two most prominent inflammatory cytokines in the inflammasome that promote the development of atherosclerosis. SGLT2 inhibitors are novel hypoglycemic agents that also have significant antiatherosclerotic effects. However, their exact mechanism is not yet clear. This article is a review of the literature on the effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, focusing on their role in antiatherosclerosis.
    Keywords:  NLRP3; SGLT2 inhibitor; atherosclerosis; diabetes mellitus; inflammasome
    DOI:  https://doi.org/10.3389/fendo.2022.992937
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