bims-longev Biomed News
on Longevity
Issue of 2023–02–12
fourteen papers selected by
Andreea Nitescu
  1. Nutritional and lifestyle management of the aging journey: A narrative review.
  2. The Cutting Edge of Epigenetic Clocks: In Search of Mechanisms Linking Aging and Mental Health.
  3. The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation.
  4. Unveiling Uterine Aging: Much More to Learn.
  5. Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review.
  6. Oxidative Stress and Aging as Risk Factors for Alzheimer's Disease and Parkinson's Disease: The Role of the Antioxidant Melatonin.
  7. Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer's Disease Progression.
  8. Cellular senescence and the host immune system in aging and age-related disorders.
  9. Circadian rhythms as modulators of brain health during development and throughout aging.
  10. Cardiovascular correlates of epigenetic aging across the adult lifespan: a population-based study.
  11. Reprogramming of ovarian aging epigenome by resveratrol.
  12. Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment.
  13. Berberine: Pharmacological features in health, disease and aging.
  14. From Cue to Meaning: The Involvement of POLD1 Gene in DNA Replication, Repair and Aging.
  1. Front Nutr. 2022 ;9 1087505
    Nutritional and lifestyle management of the aging journey: A narrative review.
    Amira Kassis, Marie-Claire Fichot, Marie-Noelle Horcajada, Astrid M H Horstman, Peter Duncan, Gabriela Bergonzelli, Nicolas Preitner, Diane Zimmermann, Nabil Bosco, Karine Vidal, Laurence Donato-Capel.
      With age, the physiological responses to occasional or regular stressors from a broad range of functions tend to change and adjust at a different pace and restoring these functions in the normal healthy range becomes increasingly challenging. Even if this natural decline is somehow unavoidable, opportunities exist to slow down and attenuate the impact of advancing age on major physiological processes which, when weakened, constitute the hallmarks of aging. This narrative review revisits the current knowledge related to the aging process and its impact on key metabolic functions including immune, digestive, nervous, musculoskeletal, and cardiovascular functions; and revisits insights into the important biological targets that could inspire effective strategies to promote healthy aging.
    Keywords:  aging; lifestyle; metabolism; nutrition; physiological changes
    DOI:  https://doi.org/10.3389/fnut.2022.1087505
  2. Biol Psychiatry. 2023 Feb 08. pii: S0006-3223(23)00057-4. [Epub ahead of print]
    The Cutting Edge of Epigenetic Clocks: In Search of Mechanisms Linking Aging and Mental Health.
    Zachary M Harvanek, Marco P Boks, Christiaan H Vinkers, Albert T Higgins-Chen.
      Individuals with psychiatric disorders are at increased risk of age-related diseases and early mortality. Recent studies demonstrate that this link between mental health and aging is reflected in epigenetic clocks, aging biomarkers based on DNA methylation. The reported relationships between epigenetic clocks and mental health are mostly correlational, and the mechanisms are poorly understood. Here, we review recent progress concerning the molecular and cellular processes underlying epigenetic clocks, as well as novel technologies enabling further studies of the causes and consequences of epigenetic aging. We then review the current literature on how epigenetic clocks relate to specific aspects of mental health, such as stress, medications, substance use, health behaviors, and symptom clusters. We propose an integrated framework where mental health and epigenetic aging are each broken down into multiple distinct processes which are then linked to each other, using stress and schizophrenia as examples. This framework incorporates the heterogeneity and complexity of both mental health conditions and aging, may help reconcile conflicting results, and provides a basis for further hypothesis-driven research in humans and model systems to investigate potentially causal mechanisms linking aging and mental health.
    Keywords:  aging; biomarkers; clocks; epigenetics; schizophrenia; stress
    DOI:  https://doi.org/10.1016/j.biopsych.2023.02.001
  3. Int J Mol Sci. 2023 Feb 03. pii: 2959. [Epub ahead of print]24(3):
    The Central Role of the NAD+ Molecule in the Development of Aging and the Prevention of Chronic Age-Related Diseases: Strategies for NAD+ Modulation.
    Borut Poljšak, Vito Kovač, Stjepan Špalj, Irina Milisav.
      The molecule NAD+ is a coenzyme for enzymes catalyzing cellular redox reactions in several metabolic pathways, encompassing glycolysis, TCA cycle, and oxidative phosphorylation, and is a substrate for NAD+-dependent enzymes. In addition to a hydride and electron transfer in redox reactions, NAD+ is a substrate for sirtuins and poly(adenosine diphosphate-ribose) polymerases and even moderate decreases in its cellular concentrations modify signaling of NAD+-consuming enzymes. Age-related reduction in cellular NAD+ concentrations results in metabolic and aging-associated disorders, while the consequences of increased NAD+ production or decreased degradation seem beneficial. This article reviews the NAD+ molecule in the development of aging and the prevention of chronic age-related diseases and discusses the strategies of NAD+ modulation for healthy aging and longevity.
    Keywords:  NAD+ levels; NAD+ precursors; PARP; sirtuin
    DOI:  https://doi.org/10.3390/ijms24032959
  4. Ageing Res Rev. 2023 Feb 08. pii: S1568-1637(23)00038-7. [Epub ahead of print] 101879
    Unveiling Uterine Aging: Much More to Learn.
    Yaling Wu, Milu Li, Jinjin Zhang, Shixuan Wang.
      Uterine aging is an important factor that impacts fertility, reproductive health, and uterus-related diseases; however, it remains poorly explored. Functionally, these disturbances have been associated with an abnormal hormonal response in the endometrium and decreased endometrial receptivity. Based on emerging evidence, these alterations are mediated via the senescence of endometrial stem cells and impaired decidualization of endometrial stromal cells. Multiple molecular activities may participate in uterine aging, including oxidative stress, inflammation, fibrosis, DNA damage response, and cellular senescence. Over the past decade, several protective strategies targeting these biological processes have afforded promising results, including stem cell therapy, anti-aging drugs, and herbal medicines. However, the currently available evidence is fragmented and scattered. Here, we summarize the most recent findings regarding uterine aging, including functional and structural alterations and potential cellular and molecular mechanisms, and discuss potential protective interventions against uterine aging. Thereby, we hope to provide a comprehensive understanding of the pathophysiological processes and underlying mechanisms associated with uterine aging, as well as improve fecundity and reproductive outcomes in females of advanced reproductive age.
    Keywords:  Fertility; Molecular mechanism; Protective strategies; Reproductive function; Uterine aging
    DOI:  https://doi.org/10.1016/j.arr.2023.101879
  5. Front Pharmacol. 2023 ;14 1083875
    Natural compounds from botanical drugs targeting mTOR signaling pathway as promising therapeutics for atherosclerosis: A review.
    Qian Wu, Qianyu Lv, Xiao'an Liu, Xuejiao Ye, Linlin Cao, Manshi Wang, Junjia Li, Yingtian Yang, Lanlan Li, Shihan Wang.
      Atherosclerosis (AS) is a chronic inflammatory disease that is a major cause of cardiovascular diseases (CVDs), including coronary artery disease, hypertension, myocardial infarction, and heart failure. Hence, the mechanisms of AS are still being explored. A growing compendium of evidence supports that the activity of the mechanistic/mammalian target of rapamycin (mTOR) is highly correlated with the risk of AS. The mTOR signaling pathway contributes to AS progression by regulating autophagy, cell senescence, immune response, and lipid metabolism. Various botanical drugs and their functional compounds have been found to exert anti- AS effects by modulating the activity of the mTOR signaling pathway. In this review, we summarize the pathogenesis of AS based on the mTOR signaling pathway from the aspects of immune response, autophagy, cell senescence, and lipid metabolism, and comb the recent advances in natural compounds from botanical drugs to inhibit the mTOR signaling pathway and delay AS development. This review will provide a new perspective on the mechanisms and precision treatments of AS.
    Keywords:  atherosclerosis; autophagy; cell senescence; herbal medicine; mTOR; mechanism; rapamycin
    DOI:  https://doi.org/10.3389/fphar.2023.1083875
  6. Int J Mol Sci. 2023 Feb 03. pii: 3022. [Epub ahead of print]24(3):
    Oxidative Stress and Aging as Risk Factors for Alzheimer's Disease and Parkinson's Disease: The Role of the Antioxidant Melatonin.
    Jana Tchekalarova, Rumiana Tzoneva.
      Aging and neurodegenerative diseases share common hallmarks, including mitochondrial dysfunction and protein aggregation. Moreover, one of the major issues of the demographic crisis today is related to the progressive rise in costs for care and maintenance of the standard living condition of aged patients with neurodegenerative diseases. There is a divergence in the etiology of neurodegenerative diseases. Still, a disturbed endogenous pro-oxidants/antioxidants balance is considered the crucial detrimental factor that makes the brain vulnerable to aging and progressive neurodegeneration. The present review focuses on the complex relationships between oxidative stress, autophagy, and the two of the most frequent neurodegenerative diseases associated with aging, Alzheimer's disease (AD) and Parkinson's disease (PD). Most of the available data support the hypothesis that a disturbed antioxidant defense system is a prerequisite for developing pathogenesis and clinical symptoms of ADs and PD. Furthermore, the release of the endogenous hormone melatonin from the pineal gland progressively diminishes with aging, and people's susceptibility to these diseases increases with age. Elucidation of the underlying mechanisms involved in deleterious conditions predisposing to neurodegeneration in aging, including the diminished role of melatonin, is important for elaborating precise treatment strategies for the pathogenesis of AD and PD.
    Keywords:  Alzheimer’s disease; Parkinson’s disease; aging; melatonin; oxidative stress
    DOI:  https://doi.org/10.3390/ijms24033022
  7. Int J Mol Sci. 2023 Jan 18. pii: 1869. [Epub ahead of print]24(3):
    Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer's Disease Progression.
    Felicia Liana Andronie-Cioara, Adriana Ioana Ardelean, Carmen Delia Nistor-Cseppento, Anamaria Jurcau, Maria Carolina Jurcau, Nicoleta Pascalau, Florin Marcu.
      Aging is the most prominent risk factor for late-onset Alzheimer's disease. Aging associates with a chronic inflammatory state both in the periphery and in the central nervous system, the evidence thereof and the mechanisms leading to chronic neuroinflammation being discussed. Nonetheless, neuroinflammation is significantly enhanced by the accumulation of amyloid beta and accelerates the progression of Alzheimer's disease through various pathways discussed in the present review. Decades of clinical trials targeting the 2 abnormal proteins in Alzheimer's disease, amyloid beta and tau, led to many failures. As such, targeting neuroinflammation via different strategies could prove a valuable therapeutic strategy, although much research is still needed to identify the appropriate time window. Active research focusing on identifying early biomarkers could help translating these novel strategies from bench to bedside.
    Keywords:  Alzheimer’s disease; TNF signaling; TREM2; cellular senescence; inflammaging; microglia; neuroinflammation; oxidative stress; therapy
    DOI:  https://doi.org/10.3390/ijms24031869
  8. Biomed J. 2023 Feb 04. pii: S2319-4170(23)00005-7. [Epub ahead of print]
    Cellular senescence and the host immune system in aging and age-related disorders.
    Yvonne Giannoula, Guido Kroemer, Federico Pietrocola.
      Cellular senescence is a complex process involving a close-to-irreversible arrest of the cell cycle, the acquisition of the senescence-associated secretory phenotype (SASP), as well as profound changes in the expression of cell surface proteins that determine the recognition of senescent cells by innate and cognate immune effectors including macrophages, NK, NKT and T cells. It is important to note that senescence can occur in a transient fashion to improve the homeostatic response of tissues to stress. Moreover, both the excessive generation and the insufficient elimination of senescent cells may contribute to pathological aging. Attempts are being made to identify the mechanisms through which senescent cell avoid their destruction by immune effectors. Such mechanisms involve the cell surface expression of immunosuppressive molecules including PD-L1 and PD-L2 to ligate PD-1 on T cells, as well as tolerogenic MHC class-I variants. In addition, senescent cells can secrete factors that attract immunosuppressive and pro-inflammatory cells into the microenvironment. Each of these immune evasion mechanism offers a target for therapeutic intervention, e.g., by blocking the interaction between PD-1 and PD-L1 or PD-L2, upregulating immunogenic MHC class-I molecules and eliminating immunosuppressive cell types. In addition, senescent cells differ in their antigenic makeup and immunopeptidome from their normal counterparts, hence offering the opportunity to stimulate immune response against senescence-associated antigens. Ideally, immunological anti-senescence strategies should succeed in selectively eliminating pathogenic senescent cells but spare homeostatic senescence.
    Keywords:  Immunity; Inflammation; NK cells; SASP; T cells; macrophages
    DOI:  https://doi.org/10.1016/j.bj.2023.02.001
  9. Front Neural Circuits. 2022 ;16 1059229
    Circadian rhythms as modulators of brain health during development and throughout aging.
    Rachel Van Drunen, Kristin Eckel-Mahan.
      The circadian clock plays a prominent role in neurons during development and throughout aging. This review covers topics pertinent to the role of 24-h rhythms in neuronal development and function, and their tendency to decline with aging. Pharmacological or behavioral modification that augment the function of our internal clock may be central to decline of cognitive disease and to future chronotherapy for aging-related diseases of the central nervous system.
    Keywords:  aging; chronotherapy; circadian; memory; suprachiasmatic nucleus; synaptic plasticity
    DOI:  https://doi.org/10.3389/fncir.2022.1059229
  10. Geroscience. 2023 Feb 08.
    Cardiovascular correlates of epigenetic aging across the adult lifespan: a population-based study.
    Dan Liu, N Ahmad Aziz, Gökhan Pehlivan, Monique M B Breteler.
      Individuals with a similar chronological age can exhibit marked differences in cardiovascular risk profiles, but it is unknown whether this variation is related to different rates of biological aging. Therefore, we investigated the relation between nine domains of cardiovascular function and four epigenetic age acceleration estimators (i.e., AgeAccel.Horvath, AgeAccel.Hannum, AgeAccelPheno, and AgeAccelGrim), derived from DNA methylation profiles. Among 4194 participants (mean age 54.2 years (range 30.0-95.0)) from the Rhineland Study, an ongoing population-based cohort study in Bonn, Germany, epigenetic age acceleration increased by 0.19-1.84 years per standard deviation (SD) increase in cardiovascular risk across multiple domains, including measures of kidney function, adiposity, and a composite cardiovascular risk score. Measures of inflammation and glucose homeostasis were associated with AgeAccel.Hannum, AgeAccelPheno, and AgeAccelGrim, but not with AgeAccel.Horvath. Moreover, effect sizes were larger for AgeAccelPheno and AgeAccelGrim than for AgeAccel.Horvath and AgeAccel.Hannum. Similarly, epigenetic age acceleration increased by 0.15-0.81 years per SD increase in markers of vascular function (blood pressure, arterial stiffness, and hemodynamic measures), whereas better endothelial function was only associated with lower AgeAccelGrim. Most effects on epigenetic age acceleration were independent, which suggests they independently contribute to different rates of biological aging.
    Keywords:  Biological age; Cardiovascular aging; Epigenetic age acceleration
    DOI:  https://doi.org/10.1007/s11357-022-00714-0
  11. PNAS Nexus. 2023 Feb;2(2): pgac310
    Reprogramming of ovarian aging epigenome by resveratrol.
    Mo Gou, Jie Li, Lizhi Yi, Huiyu Li, Xiaoying Ye, Huasong Wang, Linlin Liu, Baofa Sun, Song Zhang, Zhengmao Zhu, Jiang Liu, Lin Liu.
      Resveratrol is an antiaging, antioxidant, and anti-inflammatory natural polyphenolic compound. Growing evidence indicates that resveratrol has potential therapeutic effects for improving aging ovarian function. However, the mechanisms underlying prolonged reproductive longevity remain elusive. We found that resveratrol ameliorates ovarian aging transcriptome, some of which are associated with specific changes in methylome. In addition to known aging transcriptome of oocytes and granulosa cells such as decline in oxidoreductase activity, metabolism and mitochondria function, and elevated DNA damage and apoptosis, actin cytoskeleton are notably downregulated with age, and these defects are mostly rescued by resveratrol. Moreover, the aging-associated hypermethylation of actin cytoskeleton is decreased by resveratrol. In contrast, deletion of Tet2, involved in DNA demethylation, abrogates resveratrol-reprogrammed ovarian aging transcriptome. Consistently, Tet2 deficiency results in additional altered pathways as shown by increased mTOR and Wnt signaling, as well as reduced DNA repair and actin cytoskeleton with mouse age. Moreover, genes associated with oxidoreductase activity and oxidation-reduction process were hypermethylated in Tet2-deficient oocytes from middle-age mice treated with resveratrol, indicating that loss of Tet2 abolishes the antioxidant effect of resveratrol. Taking together, our finding provides a comprehensive landscape of transcriptome and epigenetic changes associated with ovarian aging that can be reprogrammed by resveratrol administration, and suggests that aberrantly increased DNA methylation by Tet2 deficiency promotes additional aging epigenome that cannot be effectively restored to younger state by resveratrol.
    Keywords:  cumulus cells; methylome; oocytes; ovarian aging; transcriptome
    DOI:  https://doi.org/10.1093/pnasnexus/pgac310
  12. Int J Mol Sci. 2023 Jan 20. pii: 2117. [Epub ahead of print]24(3):
    Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment.
    Irene Fatuzzo, Giovanni Francesco Niccolini, Federica Zoccali, Luca Cavalcanti, Mario Giuseppe Bellizzi, Gabriele Riccardi, Marco de Vincentiis, Marco Fiore, Carla Petrella, Antonio Minni, Christian Barbato.
      Olfactory capacity declines with aging, but increasing evidence shows that smell dysfunction is one of the early signs of prodromal neurodegenerative diseases such as Alzheimer's and Parkinson's disease. The study of olfactory ability and its role in neurodegenerative diseases arouses much interest in the scientific community. In neurology, olfactory impairment is a potential early marker for the onset of neurodegenerative diseases, but the underlying mechanism is poorly understood. The loss of smell is considered a clinical sign of early-stage disease and a marker of the disease's progression and cognitive impairment. Highlighting the importance of biological bases of smell and molecular pathways could be fundamental to improve neuroprotective and therapeutic strategies. We focused on the review articles and meta-analyses on olfactory and cognitive impairment. We depicted the neurobiology of olfaction and the most common olfactory tests in neurodegenerative diseases. In addition, we underlined the close relationship between the olfactory and cognitive deficit due to nasal neuroepithelium, which is a direct extension of the CNS in communication with the external environment. Neurons, Nose, and Neurodegenerative diseases highlights the role of olfactory dysfunction as a clinical marker for early stages of neurodegenerative diseases when it is associated with molecular, clinical, and neuropathological correlations.
    Keywords:  anosmia; cognitive dysfunction; nasal neuroepithelium; neurodegenerative disease; neurons; nose; olfactory biomarkers
    DOI:  https://doi.org/10.3390/ijms24032117
  13. Curr Med Chem. 2023 Feb 07.
    Berberine: Pharmacological features in health, disease and aging.
    Amin Gasmi, Farah Asghar, Saba Zafar, Petro Oliinyk, Oksana Khavrona, Roman Lysiuk, Massimiliano Peana, Salva Piscopo, Halyna Antonyak, Joeri J Pen, Iryna Lozynska, Sadaf Noor, Larysa Lenchyk, Akram Muhammad, Inna Vladimirova, Natalia Dub, Olha Antoniv, Oksana Tsal, Taras Upyr, Geir Bjørklund.
       BACKGROUND: Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes.
    OBJECTIVE: This review describes the role of berberine and its metabolic effects. It also discussed how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage.
    METHODS: Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022.
    RESULTS: Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, a plant alkaloid is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models.
    CONCLUSION: Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.
    Keywords:  Aging; Alternative therapy; Antimicrobial activity; Berberine; DNA; Gero-suppression; Microbial modulation; Neurodegenerative and Neuropsychological disorders; Obesity; metabolic effects
    DOI:  https://doi.org/10.2174/0929867330666230207112539
  14. Mech Ageing Dev. 2023 Feb 08. pii: S0047-6374(23)00016-7. [Epub ahead of print] 111790
    From Cue to Meaning: The Involvement of POLD1 Gene in DNA Replication, Repair and Aging.
    Michela Murdocca, Paola Spitalieri, Maria Rosaria D'Apice, Giuseppe Novelli, Federica Sangiuolo.
      Aging is an extremely complex biological process. Aging, cancer and inflammation represent a trinity, object of many interesting researches. The accumulation of DNA damage and its consequences progressively interfere with cellular function and increase susceptibility to developing aging condition. DNA Polymerase delta (Pol δ), encoded by POLD1 gene (MIM#174761) on 19q13.3, is well implicated in many steps of the replication program and repair. Thanks to its exonuclease and polymerase activities, the enzyme is involved in the regulation of the cell cycle, DNA synthesis, and DNA damage repair processes. Damaging variants within the exonuclease domain predispose to cancers, while those occurring in the polymerase active site cause the autosomal dominant Progeroid Syndrome called MDPL, Mandibular hypoplasia, Deafness and Progeroid features with concomitant Lipodystrophy Since DNA damage represents the main cause of ageing and age-related pathologies, an overview of critical Pol δ activities will allow to better understand the associations between DNA damage and nearly every aspect of the ageing process, helping the researchers to counteract all the ageing-pathologies at the same time.
    Keywords:  DNA polymerase delta; DNA repair; MDPL; aging; mithocondria
    DOI:  https://doi.org/10.1016/j.mad.2023.111790
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