bims-longev Biomed News
on Longevity
Issue of 2023–03–12
sixteen papers selected by
Andreea Nitescu
  1. Preservation of mitochondrial membrane potential is necessary for lifespan extension from dietary restriction.
  2. Putting aging on ICE.
  3. Vitamin D as a Shield against Aging.
  4. Whole organism aging: Parabiosis, inflammaging, epigenetics, and peripheral and central aging clocks. The ARS of aging.
  5. Female Reproductive Aging and Oxidative Stress: Mesenchymal Stem Cell Conditioned Medium as a Promising Antioxidant.
  6. Study of Diet Habits and Cognitive Function in the Chinese Middle-Aged and Elderly Population: The Association between Folic Acid, B Vitamins, Vitamin D, Coenzyme Q10 Supplementation and Cognitive Ability.
  7. The longevity response to warm temperature is neurally controlled via the regulation of collagen genes.
  8. Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan.
  9. Epigenetic rejuvenation by partial reprogramming.
  10. m6A methylation: Critical roles in aging and neurological diseases.
  11. Mitochondrial dysfunction in hearing loss: Oxidative stress, autophagy and NLRP3 inflammasome.
  12. The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer's Disease, Amyotrophic Lateral Sclerosis and Aging.
  13. Enhanced insulin-regulated phagocytic activities support extreme health span and longevity in multiple populations.
  14. Proteomic basis of mortality resilience mediated by FOXO3 longevity genotype.
  15. Interaction with a Virtual Coach for Active and Healthy Ageing.
  16. The Role of the National Institute on Aging in the Development of the Field of Geroscience.
  1. Geroscience. 2023 Mar 06.
    Preservation of mitochondrial membrane potential is necessary for lifespan extension from dietary restriction.
    Brandon J Berry, Evan Mjelde, Fatima Carreno, Kathryn Gilham, Emily J Hanson, Emily Na, Matt Kaeberlein.
      Dietary restriction (DR) increases lifespan in many organisms, but its underlying mechanisms are not fully understood. Mitochondria play a central role in metabolic regulation and are known to undergo changes in structure and function in response to DR. Mitochondrial membrane potential (Δψm) is the driving force for ATP production and mitochondrial outputs that integrate many cellular signals. One such signal regulated by Δψm is nutrient-status sensing. Here, we tested the hypothesis that DR promotes longevity through preserved Δψm during adulthood. Using the nematode Caenorhabditis elegans, we find that Δψm declines with age relatively early in the lifespan, and this decline is attenuated by DR. Pharmacologic depletion of Δψm blocked the longevity and health benefits of DR. Genetic perturbation of Δψm and mitochondrial ATP availability similarly prevented lifespan extension from DR. Taken together, this study provides further evidence that appropriate regulation of Δψm is a critical factor for health and longevity in response to DR.
    Keywords:  Aging; Bioenergetics; Calorie restriction; Fasting; Metabolism; Mitochondrial uncoupling
    DOI:  https://doi.org/10.1007/s11357-023-00766-w
  2. Cell Metab. 2023 Mar 07. pii: S1550-4131(23)00048-7. [Epub ahead of print]35(3): 383-385
    Putting aging on ICE.
    Bryan B Teefy, Bérénice A Benayoun.
      A recent report by Yang et al. in Cell demonstrates that faithful DNA double-strand breaks and repair cycles phenocopy many aspects of aging in mice. Whether this progeroid phenotype is caused by a loss of epigenetic information remains to be conclusively determined.
    DOI:  https://doi.org/10.1016/j.cmet.2023.02.012
  3. Int J Mol Sci. 2023 Feb 25. pii: 4546. [Epub ahead of print]24(5):
    Vitamin D as a Shield against Aging.
    Cristina Fantini, Clarissa Corinaldesi, Andrea Lenzi, Silvia Migliaccio, Clara Crescioli.
      Aging can be seen as a physiological progression of biomolecular damage and the accumulation of defective cellular components, which trigger and amplify the process, toward whole-body function weakening. Senescence initiates at the cellular level and consists in an inability to maintain homeostasis, characterized by the overexpression/aberrant expression of inflammatory/immune/stress responses. Aging is associated with significant modifications in immune system cells, toward a decline in immunosurveillance, which, in turn, leads to chronic elevation of inflammation/oxidative stress, increasing the risk of (co)morbidities. Albeit aging is a natural and unavoidable process, it can be regulated by some factors, like lifestyle and diet. Nutrition, indeed, tackles the mechanisms underlying molecular/cellular aging. Many micronutrients, i.e., vitamins and elements, can impact cell function. This review focuses on the role exerted by vitamin D in geroprotection, based on its ability to shape cellular/intracellular processes and drive the immune response toward immune protection against infections and age-related diseases. To this aim, the main biomolecular paths underlying immunosenescence and inflammaging are identified as biotargets of vitamin D. Topics such as heart and skeletal muscle cell function/dysfunction, depending on vitamin D status, are addressed, with comments on hypovitaminosis D correction by food and supplementation. Albeit research has progressed, still limitations exist in translating knowledge into clinical practice, making it necessary to focus attention on the role of vitamin D in aging, especially considering the growing number of older individuals.
    Keywords:  cardiomyocytes; immunocytes; immunosenescence; inflammaging; molecular mechanisms; skeletal muscle cells; vitamin D
    DOI:  https://doi.org/10.3390/ijms24054546
  4. Exp Gerontol. 2023 Mar 08. pii: S0531-5565(23)00058-X. [Epub ahead of print]174 112137
    Whole organism aging: Parabiosis, inflammaging, epigenetics, and peripheral and central aging clocks. The ARS of aging.
    Reinald Pamplona, Mariona Jové, José Gómez, Gustavo Barja.
      The strong interest shown in the study of the causes of aging in recent decades has uncovered many mechanisms that could contribute to the rate of aging. These include mitochondrial ROS production, DNA modification and repair, lipid peroxidation-induced membrane fatty acid unsaturation, autophagy, telomere shortening rate, apoptosis, proteostasis, senescent cells, and most likely there are many others waiting to be discovered. However, all these well-known mechanisms work only or mainly at the cellular level. Although it is known that organs within a single individual do not age at exactly the same rate, there is a well-defined species longevity. Therefore, loose coordination of aging rate among the different cells and tissues is needed to ensure species lifespan. In this article we focus on less known extracellular, systemic, and whole organism level mechanisms that could loosely coordinate aging of the whole individual to keep it within the margins of its species longevity. We discuss heterochronic parabiosis experiments, systemic factors distributed through the vascular system like DAMPs, mitochondrial DNA and its fragments, TF-like vascular proteins, and inflammaging, as well as epigenetic and proposed aging clocks situated at different levels of organization from individual cells to the brain. These interorgan systems can help to determine species longevity as a further adaptation to the ecosystem.
    Keywords:  Aging; Aging clocks; Epigenetics; Inflammaging; Parabiosis
    DOI:  https://doi.org/10.1016/j.exger.2023.112137
  5. Int J Mol Sci. 2023 Mar 06. pii: 5053. [Epub ahead of print]24(5):
    Female Reproductive Aging and Oxidative Stress: Mesenchymal Stem Cell Conditioned Medium as a Promising Antioxidant.
    Kihae Ra, Se Chang Park, Byeong Chun Lee.
      The recent tendency to delay pregnancy has increased the incidence of age-related infertility, as female reproductive competence decreases with aging. Along with aging, a lowered capacity of antioxidant defense causes a loss of normal function in the ovaries and uterus due to oxidative damage. Therefore, advancements have been made in assisted reproduction to resolve infertility caused by reproductive aging and oxidative stress, following an emphasis on their use. The application of mesenchymal stem cells (MSCs) with intensive antioxidative properties has been extensively validated as a regenerative therapy, and proceeding from original cell therapy, the therapeutic effects of stem cell conditioned medium (CM) containing paracrine factors secreted during cell culture have been reported to be as effective as that of direct treatment of source cells. In this review, we summarized the current understanding of female reproductive aging and oxidative stress and present MSC-CM, which could be developed as a promising antioxidant intervention for assisted reproductive technology.
    Keywords:  antioxidant; assisted reproductive technologies; female reproduction; infertility; mesenchymal stem cell; oxidative stress; reproductive aging; stem cell conditioned medium
    DOI:  https://doi.org/10.3390/ijms24055053
  6. Nutrients. 2023 Mar 01. pii: 1243. [Epub ahead of print]15(5):
    Study of Diet Habits and Cognitive Function in the Chinese Middle-Aged and Elderly Population: The Association between Folic Acid, B Vitamins, Vitamin D, Coenzyme Q10 Supplementation and Cognitive Ability.
    Xinting Jiang, Yihan Guo, Liang Cui, Lin Huang, Qihao Guo, Gaozhong Huang.
      A growing body of evidence suggests that vitamin supplements play a role in the prevention of cognitive decline. The objective of the present cross-sectional study was to evaluate the relationship between cognitive ability and folic acid, B vitamins, vitamin D (VD) and Coenzyme Q10 (CoQ10) supplementation. The sample consisted of 892 adults aged above 50 who were assessed for their cognitive status in the Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine (China) from July 2019 to January 2022. According to the degree of cognitive impairment, the subjects were divided into a normal control (NC) group, subjective cognitive decline (SCD) group, mild cognitive impairment (MCI) group and Alzheimer's disease (AD) group. The results indicated a lower risk of AD in the daily VD-supplemented subjects with MCI compared to those who were not supplemented; a lower risk of cognitive impairment in those with normal cognitive who consumed VD, folic acid or CoQ10 on a daily basis compared those who did not; and a lower risk of cognitive impairment in subjects with normal cognitive performance who consumed B vitamin supplements, either daily or occasionally, compared to those who did not. The correlation was independent of other factors that potentially affect cognition, such as education level, age, etc. In conclusion, our findings confirmed a lower prevalence of cognitive impairment in those who took vitamins (folic acid, B vitamins, VD, CoQ10) daily. Therefore, we would recommend daily supplementation of vitamins (folic acid, B vitamins, VD, CoQ10), especially group B vitamins, as a potential preventive measure to slow cognitive decline and neurodegeneration in the elderly. However, for the elderly who have already suffered from cognitive impairment, VD supplementation may also be beneficial for their brains.
    Keywords:  B vitamins; coenzyme Q10; cognitive impairment; folic acid; vitamin D; vitamins
    DOI:  https://doi.org/10.3390/nu15051243
  7. Aging Cell. 2023 Mar 09. e13815
    The longevity response to warm temperature is neurally controlled via the regulation of collagen genes.
    Sankara Naynar Palani, Durai Sellegounder, Phillip Wibisono, Yiyong Liu.
      Studies in diverse species have associated higher temperatures with shorter lifespan and lower temperatures with longer lifespan. These inverse effects of temperature on longevity are traditionally explained using the rate of living theory, which posits that higher temperatures increase chemical reaction rates, thus speeding up the aging process. Recent studies have identified specific molecules and cells that affect the longevity response to temperature, indicating that this response is regulated, not simply thermodynamic. Here, we demonstrate that in Caenorhabditis elegans, functional loss of NPR-8, a G protein-coupled receptor related to mammalian neuropeptide Y receptors, increases worm lifespan at 25°C but not at 20°C or 15°C, and that the lifespan extension at 25°C is regulated by the NPR-8-expressing AWB and AWC chemosensory neurons as well as AFD thermosensory neurons. Integrative transcriptomic analyses revealed that both warm temperature and old age profoundly alter gene expression and that genes involved in the metabolic and biosynthetic processes increase expression at 25°C relative to 20°C, indicating elevated metabolism at warm temperature. These data demonstrate that the temperature-induced longevity response is neurally regulated and also provide a partial molecular basis for the rate of living theory, suggesting that these two views are not mutually exclusive. Genetic manipulation and functional assays further uncovered that the NPR-8-dependent longevity response to warm temperature is achieved by regulating the expression of a subset of collagen genes. As increased collagen expression is a common feature of many lifespan-extending interventions and enhanced stress resistance, collagen expression could be critical for healthy aging.
    Keywords:   C. elegans ; G protein-coupled receptor; NPR-8; aging; gene expression; lifespan; longevity; metabolic rate; neuroscience; signal transduction
    DOI:  https://doi.org/10.1111/acel.13815
  8. Nat Aging. 2023 Feb;3(2): 157-161
    Optogenetic rejuvenation of mitochondrial membrane potential extends C. elegans lifespan.
    Brandon J Berry, Anežka Vodičková, Annika Müller-Eigner, Chen Meng, Christina Ludwig, Matt Kaeberlein, Shahaf Peleg, Andrew P Wojtovich.
      Mitochondrial dysfunction plays a central role in aging but the exact biological causes are still being determined. Here, we show that optogenetically increasing mitochondrial membrane potential during adulthood using a light-activated proton pump improves age-associated phenotypes and extends lifespan in C. elegans. Our findings provide direct causal evidence that rescuing the age-related decline in mitochondrial membrane potential is sufficient to slow the rate of aging and extend healthspan and lifespan.
    DOI:  https://doi.org/10.1038/s43587-022-00340-7
  9. Bioessays. 2023 Mar 04. e2200208
    Epigenetic rejuvenation by partial reprogramming.
    Deepika Puri, Wolfgang Wagner.
      Rejuvenation of cells by reprogramming toward the pluripotent state raises increasing attention. In fact, generation of induced pluripotent stem cells (iPSCs) completely reverses age-associated molecular features, including elongation of telomeres, resetting of epigenetic clocks and age-associated transcriptomic changes, and even evasion of replicative senescence. However, reprogramming into iPSCs also entails complete de-differentiation with loss of cellular identity, as well as the risk of teratoma formation in anti-ageing treatment paradigms. Recent studies indicate that partial reprogramming by limited exposure to reprogramming factors can reset epigenetic ageing clocks while maintaining cellular identity. So far, there is no commonly accepted definition of partial reprogramming, which is alternatively called interrupted reprogramming, and it remains to be elucidated how the process can be controlled and if it resembles a stable intermediate state. In this review, we discuss if the rejuvenation program can be uncoupled from the pluripotency program or if ageing and cell fate determination are inextricably linked. Alternative rejuvenation approaches with reprogramming into a pluripotent state, partial reprogramming, transdifferentiation, and the possibility of selective resetting of cellular clocks are also discussed.
    Keywords:  DNA methylation; ageing clock; epigenetic; iPSC; interrupted reprogramming; partial reprogramming; pluripotent; rejuvenation; reprogramming; transient reprogramming
    DOI:  https://doi.org/10.1002/bies.202200208
  10. Front Mol Neurosci. 2023 ;16 1102147
    m6A methylation: Critical roles in aging and neurological diseases.
    Yishu Fan, Xinyi Lv, Zhuohui Chen, Yanyi Peng, Mengqi Zhang.
      N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells, which participates in the functional regulation of various biological processes. It regulates the expression of targeted genes by affecting RNA translocation, alternative splicing, maturation, stability, and degradation. As recent evidence shows, of all organs, brain has the highest abundance of m6A methylation of RNAs, which indicates its regulating role in central nervous system (CNS) development and the remodeling of the cerebrovascular system. Recent studies have shown that altered m6A levels are crucial in the aging process and the onset and progression of age-related diseases. Considering that the incidence of cerebrovascular and degenerative neurologic diseases increase with aging, the importance of m6A in neurological manifestations cannot be ignored. In this manuscript, we focus on the role of m6A methylation in aging and neurological manifestations, hoping to provide a new direction for the molecular mechanism and novel therapeutic targets.
    Keywords:  6-methyladenosine; CNS diseases; RNA methylation; m6A; neurovascular unit
    DOI:  https://doi.org/10.3389/fnmol.2023.1102147
  11. Front Cell Dev Biol. 2023 ;11 1119773
    Mitochondrial dysfunction in hearing loss: Oxidative stress, autophagy and NLRP3 inflammasome.
    Peipei Li, Shen Li, Le Wang, Hongmin Li, Yang Wang, Hongbing Liu, Xin Wang, Xiaodan Zhu, Zhangsuo Liu, Fanglei Ye, Yuan Zhang.
      Sensorineural deafness becomes an inevitable worldwide healthy problem, yet the current curative therapy is limited. Emerging evidences demonstrate mitochondrial dysfunction plays a vital role of in the pathogenesis of deafness. Reactive oxygen species (ROS)-induced mitochondrial dysfunction combined with NLRP3 inflammasome activation is involved in cochlear damage. Autophagy not only clears up undesired proteins and damaged mitochondria (mitophagy), but also eliminate excessive ROS. Appropriate enhancement of autophagy can reduce oxidative stress, inhibit cell apoptosis, and protect auditory cells. In addition, we further discuss the interplays linking ROS generation, NLRP3 inflammasome activation, and autophagy underlying the pathogenesis of deafness, including ototoxic drugs-, noise- and aging-related hearing loss.
    Keywords:  NLRP3 inflammasome; autophagy; hearing loss; mitochondrial dysfunction; oxidative stress
    DOI:  https://doi.org/10.3389/fcell.2023.1119773
  12. Cells. 2023 Feb 27. pii: 763. [Epub ahead of print]12(5):
    The Neuroprotective Activities of the Novel Multi-Target Iron-Chelators in Models of Alzheimer's Disease, Amyotrophic Lateral Sclerosis and Aging.
    Lana Kupershmidt, Moussa B H Youdim.
      The concept of chelation therapy as a valuable therapeutic approach in neurological disorders led us to develop multi-target, non-toxic, lipophilic, brain-permeable compounds with iron chelation and anti-apoptotic properties for neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), age-related dementia and amyotrophic lateral sclerosis (ALS). Herein, we reviewed our two most effective such compounds, M30 and HLA20, based on a multimodal drug design paradigm. The compounds have been tested for their mechanisms of action using animal and cellular models such as APP/PS1 AD transgenic (Tg) mice, G93A-SOD1 mutant ALS Tg mice, C57BL/6 mice, Neuroblastoma × Spinal Cord-34 (NSC-34) hybrid cells, a battery of behavior tests, and various immunohistochemical and biochemical techniques. These novel iron chelators exhibit neuroprotective activities by attenuating relevant neurodegenerative pathology, promoting positive behavior changes, and up-regulating neuroprotective signaling pathways. Taken together, these results suggest that our multifunctional iron-chelating compounds can upregulate several neuroprotective-adaptive mechanisms and pro-survival signaling pathways in the brain and might function as ideal drugs for neurodegenerative disorders, such as PD, AD, ALS, and aging-related cognitive decline, in which oxidative stress and iron-mediated toxicity and dysregulation of iron homeostasis have been implicated.
    Keywords:  Alzheimer’s disease; amyloid precursor protein; amyotrophic lateral sclerosis; erythropoietin; iron; iron chelator; monoamine oxidase; neuroprotection; oxidative stress; tau protein
    DOI:  https://doi.org/10.3390/cells12050763
  13. Aging Cell. 2023 Mar 08. e13810
    Enhanced insulin-regulated phagocytic activities support extreme health span and longevity in multiple populations.
    Deng Wu, Xiaoman Bi, Peihu Li, Dahua Xu, Jianmin Qiu, Kongning Li, Shaojiang Zheng, Kim Hei-Man Chow.
      The immune system plays a central role in many processes of age-related disorders and it remains unclear if the innate immune system may play roles in shaping extreme longevity. By an integrated analysis with multiple bulk and single cell transcriptomic, so as DNA methylomic datasets of white blood cells, a previously unappreciated yet commonly activated status of the innate monocyte phagocytic activities is identified. Detailed analyses revealed that the life cycle of these monocytes is enhanced and primed to a M2-like macrophage phenotype. Functional characterization unexpectedly revealed an insulin-driven immunometabolic network which supports multiple aspects of phagocytosis. Such reprogramming is associated to a skewed trend of DNA demethylation at the promoter regions of multiple phagocytic genes, so as a direct transcriptional effect induced by nuclear-localized insulin receptor. Together, these highlighted that preservation of insulin sensitivity is a key to healthy lifespan and extended longevity, via boosting the function of innate immune system in advanced ages.
    Keywords:  extended longevity; healthy lifespan; innate immune system; insulin sensitivity
    DOI:  https://doi.org/10.1111/acel.13810
  14. Geroscience. 2023 Mar 07.
    Proteomic basis of mortality resilience mediated by FOXO3 longevity genotype.
    Timothy A Donlon, Brian J Morris, Randi Chen, Eunjung Lim, Eric K Morgen, Kristen Fortney, Naisha Shah, Kamal H Masaki, Bradley J Willcox.
      FOXO3 is a ubiquitous transcription factor expressed in response to cellular stress caused by nutrient deprivation, inflammatory cytokines, reactive oxygen species, radiation, hypoxia, and other factors. We showed previously that the association of inherited FOXO3 variants with longevity was the result of partial protection against mortality risk posed by aging-related life-long stressors, particularly cardiometabolic disease. We then referred to the longevity-associated genotypes as conferring "mortality resilience." Serum proteins whose levels change with aging and are associated with mortality risk may be considered as "stress proteins." They may serve as indirect measures of life-long stress. Our aims were to (1) identify stress proteins that increase with aging and are associated with an increased risk of mortality, and (2) to determine if FOXO3 longevity/resilience genotype dampens the expected increase in mortality risk they pose. A total of 4500 serum protein aptamers were quantified using the Somalogic SomaScan proteomics platform in the current study of 975 men aged 71-83 years. Stress proteins associated with mortality were identified. We then used age-adjusted multivariable Cox models to investigate the interaction of stress protein with FOXO3 longevity-associated rs12212067 genotypes. For all the analyses, the p values were corrected for multiple comparisons by false discovery rate. This led to the identification of 44 stress proteins influencing the association of FOXO3 genotype with reduced mortality. Biological pathways were identified for these proteins. Our results suggest that the FOXO3 resilience genotype functions by reducing mortality in pathways related to innate immunity, bone morphogenetic protein signaling, leukocyte migration, and growth factor response.
    Keywords:  Bone morphogenic protein signaling; Cardiometabolic disease; Cytokines; Disease resilience; FOXO3; Genetics; Inflammation
    DOI:  https://doi.org/10.1007/s11357-023-00740-6
  15. Sensors (Basel). 2023 Mar 02. pii: 2748. [Epub ahead of print]23(5):
    Interaction with a Virtual Coach for Active and Healthy Ageing.
    Michael McTear, Kristiina Jokinen, Mirza Mohtashim Alam, Qasid Saleem, Giulio Napolitano, Florian Szczepaniak, Mossaab Hariz, Gérard Chollet, Christophe Lohr, Jérôme Boudy, Zohre Azimi, Sonja Dana Roelen, Rainer Wieching.
      Since life expectancy has increased significantly over the past century, society is being forced to discover innovative ways to support active aging and elderly care. The e-VITA project, which receives funding from both the European Union and Japan, is built on a cutting edge method of virtual coaching that focuses on the key areas of active and healthy aging. The requirements for the virtual coach were ascertained through a process of participatory design in workshops, focus groups, and living laboratories in Germany, France, Italy, and Japan. Several use cases were then chosen for development utilising the open-source Rasa framework. The system uses common representations such as Knowledge Bases and Knowledge Graphs to enable the integration of context, subject expertise, and multimodal data, and is available in English, German, French, Italian, and Japanese.
    Keywords:  active and healthy ageing; dialogue system; knowledge sources; participatory design; sensors
    DOI:  https://doi.org/10.3390/s23052748
  16. Cold Spring Harb Perspect Med. 2023 Mar 06. pii: a041211. [Epub ahead of print]
    The Role of the National Institute on Aging in the Development of the Field of Geroscience.
    Felipe Sierra, Ronald A Kohanski.
      The conceptualization of the field of geroscience, which began about 10 years ago, marks, together with the publication of "The hallmarks of aging" (see López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Cell 153: 1194-1217, 2013), a significant watershed in the development of aging research. Based on a very simple and commonly accepted premise, namely, that aging biology is at the core the most significant risk factor for all chronic diseases affecting the elderly, geroscience became possible because of earlier significant developments in the field of aging biology. Here we describe the origins of the concept, as well as its current status in the field. The principles of geroscience provide an important new biomedical perspective and have spawned a significantly increased interest in aging biology within the larger biomedical scientific community.
    DOI:  https://doi.org/10.1101/cshperspect.a041211
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