bims-caglex 2024-04-28 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2024–04–28
twenty papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Dual-Acting Nitric Oxide Donor and Phosphodiesterase Inhibitor TOP-N53 Increases Lifespan and Health Span of Caenorhabditis elegans.
Candidate molecular targets uncovered in mouse lifespan extension studies.
Mitochondrial dysfunction, a weakest link of network of aging, relation to innate intramitochondrial immunity of DNA recognition receptors.
Total ginsenosides extend healthspan of aging Drosophila by suppressing imbalances in intestinal stem cells and microbiota.
Unlocking the Therapeutic Potential of Marine Collagen: A Scientific Exploration for Delaying Skin Aging.
SuperAgers and Centenarians, Dynamics of Healthy Ageing with Cognitive Resilience.
Profiling microRNA expression during senescence and aging: mining for a diagnostic tool of senescent-cell burden.
Influence of Adipokines on Metabolic Dysfunction and Aging.
Cell Senescence in Heterotopic Ossification.
STING promotes homeostatic maintenance of tissues and confers longevity with aging.
Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy.
Progress in Understanding Oxidative Stress, Aging, and Aging-Related Diseases.
Protective effects of Aureobasidium pullulans lysate on UV-damaged human skin fibroblasts and HaCaT cells.
Reprogramming T cells as an emerging treatment to slow human age-related decline in health.
Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina.
Hyaluronic Acid Based Adipose Tissue-Derived Extracellular Matrix Scaffold in Wound Healing: Histological and Immunohistochemical Study.
Food, Dietary Supplements and Nutraceuticals in Aging and Neurodegenerative Diseases.
Highlight of 2023: Unraveling the complexity of T cell aging - insights from recent advances.
Applications of Exosomal miRNAs from Mesenchymal Stem Cells as Skin Boosters.
Use of platelet rich plasma for skin rejuvenation.

MicroPubl Biol. 2024 ;2024

Dual-Acting Nitric Oxide Donor and Phosphodiesterase Inhibitor TOP-N53 Increases Lifespan and Health Span of Caenorhabditis elegans.

Martina Rudgalvyte, Paola Atzei, Rita de Brito Francisco, Reto Naef, Dominique A Glauser.

The quest for extending lifespan and promoting a healthy aging has been a longstanding pursuit in the field of aging research. The control of aging and age-related diseases by nitric oxide (NO) and cGMP signaling is a broadly conserved process from worms to human. Here we show that TOP-N53, a dual-acting NO donor and PDE5 inhibitor, can increase both lifespan and health span in C. elegans .

DOI: https://doi.org/10.17912/micropub.biology.001090
Expert Opin Ther Targets. 2024 Apr 24.

Candidate molecular targets uncovered in mouse lifespan extension studies.

Maria Vedunova, Olga Borysova, Georgiy Kozlov, Anna-Maria Zharova, Ivan Morgunov, Alexey Moskalev.

   INTRODUCTION: Multiple interventions have demonstrated an increase in mouse lifespan. However, non-standardized controls, sex or strain-specific factors, and insufficient focus on targets, hinder the translation of these findings into clinical applications.
AREAS COVERED: We examined the effects of genetic and drug-based interventions on mice from databases DrugAge, GenAge, the Mouse Phenome Database, and publications from PubMed that led to a lifespan extension of more than 10%, identifying specific molecular targets that were manipulated to achieve the maximum lifespan in mice. Subsequently, we characterized 10 molecular targets influenced by these interventions, with particular attention given to clinical trials and potential indications for each.
EXPERT OPINION: To increase the translational potential of mice life-extension studies to clinical research several factors are crucial: standardization of mice lifespan research approaches, the development of clear criteria for control and experimental groups, the establishment of criteria for potential geroprotectors, and focusing on targets and their clinical application. Pinpointing the targets affected by geroprotectors helps in understanding species-specific differences and identifying potential side effects, ensuring the safety and effectiveness of clinical trials. Additionally, target review facilitates the optimization of treatment protocols and the evaluation of the clinical feasibility of translating research findings into practical therapies for humans.

Keywords:  Aging; geroprotectors; interventions; lifespan; longevity; targets; therapy

DOI:  https://doi.org/10.1080/14728222.2024.2346597
Mitochondrion. 2024 Apr 23. pii: S1567-7249(24)00044-8. [Epub ahead of print] 101886

Mitochondrial dysfunction, a weakest link of network of aging, relation to innate intramitochondrial immunity of DNA recognition receptors.

Dun-Xian Tan.

  Aging probably is the most complexed process in biology. It is manifested by a variety of hallmarks. These hallmarks weave a network of aging; however, each hallmark is not uniformly strong for the network. It is the weakest link determining the strengthening of the network of aging, or the maximum lifespan of an organism. Therefore, only improvement of the weakest link has the chance to increase the maximum lifespan but not others. We hypothesize that mitochondrial dysfunction is the weakest link of the network of aging. It may origin from the innate intramitochondrial immunity related to the activity of pathogen DNA recognition receptors. These receptors recognize mtDNA as the PAMP or DAMP to initiate the immune or inflammatory reactions. Evidence has shown that several of these receptors including TLR9, cGAS and IFI16 can be translocated into mitochondria. The potentially intramitochondrial pathogen DNA recognition receptors have the capacity to attack the exposed second structures of the mtDNA during its transcriptional or especially the replication processed, leading to the mtDNA mutation, deletion, heteroplasmy colonization, mitochondrial dysfunction, and alterations of other hallmarks, as well as aging. Pre-consumption of the intramitochondrial pathogen DNA recognition receptors by medical interventions including development of mitochondrial targeted small molecule which can neutralization of these receptors may retard or even reverse the aging to significantly improve the maximum lifespan of the organisms.

Keywords:  Aging; DNA recognition receptors; Hallmarks of aging; Innate intracellular immunity; Mitochondria dysfunction; mtDNA deletion

DOI:  https://doi.org/10.1016/j.mito.2024.101886
Phytomedicine. 2024 Apr 16. pii: S0944-7113(24)00309-X. [Epub ahead of print]129 155650

Total ginsenosides extend healthspan of aging Drosophila by suppressing imbalances in intestinal stem cells and microbiota.

Ying Liu, Xinran Wang, Chenrong Jin, Juhui Qiao, Chenxi Wang, Leilei Jiang, Shiting Yu, Daian Pan, Daqing Zhao, Siming Wang, Meichen Liu.

   BACKGROUND: Disruption of stem cell and microbial homeostasis accelerates the aging process. Hence, maintaining these balances effectively delays aging and alleviates the symptoms of age-related diseases. Recent research indicates that targeting endoplasmic reticulum (ER) stress and immune deficiency (IMD) signalling may play a positive role in maintaining homeostasis in aging intestinal stem cells (ISC) and microbial equilibrium. Previous research has suggested that total ginsenosides (TG) derived from Panax ginseng C. A. Meyer may exhibit potential anti-aging properties by mitigating ER stress and mediating the IMD pathway. Nevertheless, it remains unclear whether TG improve ISC and microbial homeostasis by modulating ER stress and the IMD pathway to promote healthy aging.
PURPOSE: To elucidate whether TG promotes healthspan in Drosophila and its underlying molecular mechanisms, focusing on its role in regulating ER stress and the IMD pathway to maintain ISC and intestinal microbiota homeostasis.
METHODS: High performance liquid chromatography was performed to detect the main saponin monomer in TG. Survival rate, gut length, barrier function, and feeding/excretion behaviour assays were used to evaluate the effects of TG on the lifespan and gut health of Drosophila. At the stem cell level, "esg-luciferase" reporter system, esg-GFP/delta stem cell fluorescent labelling, and phospho-histone H3+ mitotic activity assays were employed to determine whether TG prevented natural aging or oxidative stress-associated ISC over-proliferation in Drosophila. Immunofluorescence staining was used to detect the effects of TG on ER stress during aging. Overexpression or interference of ER stress target genes and their related c-Jun N-terminal kinase (JNK) gene was manipulated using gene editing technology to verify the molecular mechanism by which TG maintains age-related ISC proliferation homeostasis. Molecular docking and isothermal titration calorimetry were used to verify the direct interactions between TG and ER stress target genes. In addition, at the intestinal flora level, 16S rDNA sequencing was used to analyse the effect of TG on the diversity and abundance of Drosophila intestinal flora and the possible functional pathways involved. RT-qPCR was performed to determine whether TG mediated the expression of target genes in the IMD pathway. A dominant bacterial species-specific mono-association analysis were performed to verify whether the effects of TG on IMD target genes and ISC proliferation depended on the direct control of the dominant bacterial species.
RESULTS: Our results suggest that administration of TG delays the decline in gut morphology and function in aging Drosophila. TG prevents age-associated ISC hyperproliferation by inhibiting ER stress IRE1-mediated JNK signaling. Furthermore, oral TG prevented aging-associated ISC and gut microbiota dysbiosis by remodelling the gut microbiota and inhibiting Acetobacter-mediated activation of IMD target genes.
CONCLUSION: TG promotes healthy aging by inhibiting the excessive proliferation of ISC and alleviating intestinal microbial imbalance, thereby providing new insights for the research and development of anti-aging TG products.

Keywords:  Aging; Endoplasmic reticulum stress; IMD; Intestinal stem cells; Microbiota; Total ginsenosides

DOI:  https://doi.org/10.1016/j.phymed.2024.155650
Mar Drugs. 2024 Mar 30. pii: 159. [Epub ahead of print]22(4):

Unlocking the Therapeutic Potential of Marine Collagen: A Scientific Exploration for Delaying Skin Aging.

Azizur Rahman, Rameesha Rehmani, Diana Gabby Pirvu, Siqi Maggie Huang, Simron Puri, Mateo Arcos.

  Aging is closely associated with collagen degradation, impacting the structure and strength of the muscles, joints, bones, and skin. The continuous aging of the skin is a natural process that is influenced by extrinsic factors such as UV exposure, dietary patterns, smoking habits, and cosmetic supplements. Supplements that contain collagen can act as remedies that help restore vitality and youth to the skin, helping combat aging. Notably, collagen supplements enriched with essential amino acids such as proline and glycine, along with marine fish collagen, have become popular for their safety and effectiveness in mitigating the aging process. To compile the relevant literature on the anti-aging applications of marine collagen, a search and analysis of peer-reviewed papers was conducted using PubMed, Cochrane Library, Web of Science, and Embase, covering publications from 1991 to 2024. From in vitro to in vivo experiments, the reviewed studies elucidate the anti-aging benefits of marine collagen, emphasizing its role in combating skin aging by minimizing oxidative stress, photodamage, and the appearance of wrinkles. Various bioactive marine peptides exhibit diverse anti-aging properties, including free radical scavenging, apoptosis inhibition, lifespan extension in various organisms, and protective effects in aging humans. Furthermore, the topical application of hyaluronic acid is discussed as a mechanism to increase collagen production and skin moisture, contributing to the anti-aging effects of collagen supplementation. The integration of bio-tissue engineering in marine collagen applications is also explored, highlighting its proven utility in skin healing and bone regeneration applications. However, limitations to the scope of its application exist. Thus, by delving into these nuanced considerations, this review contributes to a comprehensive understanding of the potential and challenges associated with marine collagen in the realm of anti-aging applications.

Keywords:  anti-aging; antioxidant; biopeptide; bone regeneration; extracellular matrix (ECM); fish collagen; marine collagen; prevention; skin

DOI:  https://doi.org/10.3390/md22040159
Mech Ageing Dev. 2024 Apr 22. pii: S0047-6374(24)00036-8. [Epub ahead of print] 111936

SuperAgers and Centenarians, Dynamics of Healthy Ageing with Cognitive Resilience.

Md Ariful Islam, Ujala Sehar, Omme Fatema Sultana, Upasana Mukherjee, Malcolm Brownell, Sudhir Kshirsagar, P Hemachandra Reddy.

  Graceful healthy ageing and extended longevity is the most desired goal for human race. The process of ageing is inevitable and has a profound impact on the gradual deterioration of our physiology and health since it triggers the onset of many chronic conditions like dementia, osteoporosis, diabetes, arthritis, cancer, and cardiovascular disease. However, some people who lived/live more than 100 years called 'Centenarians" and how do they achieve their extended lifespans are not completely understood. Studying these unknown factors of longevity is important not only to establish a longer human lifespan but also to manage and treat people with shortened lifespans suffering from age-related morbidities. Furthermore, older adults who maintain strong cognitive function are referred to as "SuperAgers" and may be resistant to risk factors linked to cognitive decline. Investigating the mechanisms underlying their cognitive resilience may contribute to the development of therapeutic strategies that support the preservation of cognitive function as people age. The key to a long, physically, and cognitively healthy life has been a mystery to scientists for ages. Developments in the medical sciences helps us to a better understanding of human physiological function and greater access to medical care has led us to an increase in life expectancy. Moreover, inheriting favorable genetic traits and adopting a healthy lifestyle play pivotal roles in promoting longer and healthier lives. Engaging in regular physical activity, maintaining a balanced diet, and avoiding harmful habits such as smoking contribute to overall well-being. The synergy between positive lifestyle choices, access to education, socio-economic factors, environmental determinants and genetic supremacy enhances the potential for a longer and healthier life. Our article aims to examine the factors associated with healthy ageing, particularly focusing on cognitive health in centenarians. We will also be discussing different aspects of ageing including genomic instability, metabolic burden, oxidative stress and inflammation, mitochondrial dysfunction, cellular senescence, immunosenescence, and sarcopenia.

Keywords:  Centenarians; DNA damage; Epigenetic alterations; Healthy ageing; Inflammation; Mitochondrial dysfunction; Senescence; and depletion of stem cells

DOI:  https://doi.org/10.1016/j.mad.2024.111936
bioRxiv. 2024 Apr 10. pii: 2024.04.10.588794. [Epub ahead of print]

Profiling microRNA expression during senescence and aging: mining for a diagnostic tool of senescent-cell burden.

Moritz Weigl, Teresa L Krammer, Marianne Pultar, Matthias Wieser, Selim Chaib, Masayoshi Suda, Andreas Diendorfer, Kseniya Khamina-Kotisch, Nino Giorgadze, Tamar Pirtskhalava, Kurt O Johnson, Christina L Inman, Ailing Xue, Ingo Lämmermann, Barbara Meixner, Lichao Wang, Ming Xu, Regina Grillari, Mikolaj Ogrodnik, Tamar Tchkonia, Matthias Hackl, James L Kirkland, Johannes Grillari.

In the last decade cellular senescence, a hallmark of aging, has come into focus for pharmacologically targeting aging processes. Senolytics are one of these interventive strategies that have advanced into clinical trials, creating an unmet need for minimally invasive biomarkers of senescent cell load to identify patients at need for senotherapy. We created a landscape of miRNA and mRNA expression in five human cell types induced to senescence in-vitro and provide proof-of-principle evidence that miRNA expression can track senescence burden dynamically in-vivo using transgenic p21 high senescent cell clearance in HFD fed mice. Finally, we profiled miRNA expression in seven different tissues, total plasma, and plasma derived EVs of young and 25 months old mice. In a systematic analysis, we identified 22 candidate senomiRs with potential to serve as circulating biomarkers of senescence not only in rodents, but also in upcoming human clinical senolytic trials.

DOI: https://doi.org/10.1101/2024.04.10.588794
Biomedicines. 2024 Apr 15. pii: 873. [Epub ahead of print]12(4):

Influence of Adipokines on Metabolic Dysfunction and Aging.

Seongjoon Park, Isao Shimokawa.

  Currently, 30% of the global population is overweight or obese, with projections from the World Obesity Federation suggesting that this figure will surpass 50% by 2035. Adipose tissue dysfunction, a primary characteristic of obesity, is closely associated with an increased risk of metabolic abnormalities, such as hypertension, hyperglycemia, and dyslipidemia, collectively termed metabolic syndrome. In particular, visceral fat accretion is considered as a hallmark of aging and is strongly linked to higher mortality rates in humans. Adipokines, bioactive peptides secreted by adipose tissue, play crucial roles in regulating appetite, satiety, adiposity, and metabolic balance, thereby rendering them key players in alleviating metabolic diseases and potentially extending health span. In this review, we elucidated the role of adipokines in the development of obesity and related metabolic disorders while also exploring the potential of certain adipokines as candidates for longevity interventions.

Keywords:  adipokine; adipose tissue; aging; health span; metabolic dysfunction

DOI:  https://doi.org/10.3390/biomedicines12040873
Biomolecules. 2024 Apr 16. pii: 485. [Epub ahead of print]14(4):

Cell Senescence in Heterotopic Ossification.

Robert J Pignolo, Frederick S Kaplan, Haitao Wang.

  The formation of bone outside the normal skeleton, or heterotopic ossification (HO), occurs through genetic and acquired mechanisms. Fibrodysplasia ossificans progressiva (FOP), the most devastating genetic condition of HO, is due to mutations in the ACVR1/ALK2 gene and is relentlessly progressive. Acquired HO is mostly precipitated by injury or orthopedic surgical procedures but can also be associated with certain conditions related to aging. Cellular senescence is a hallmark of aging and thought to be a tumor-suppressive mechanism with characteristic features such as irreversible growth arrest, apoptosis resistance, and an inflammatory senescence-associated secretory phenotype (SASP). Here, we review possible roles for cellular senescence in HO and how targeting senescent cells may provide new therapeutic approaches to both FOP and acquired forms of HO.

Keywords:  cellular senescence; fibrodysplasia ossificans progressiva; heterotopic ossification; senotherapeutics

DOI:  https://doi.org/10.3390/biom14040485
bioRxiv. 2024 Apr 08. pii: 2024.04.04.588107. [Epub ahead of print]

STING promotes homeostatic maintenance of tissues and confers longevity with aging.

Jacob W Hopkins, Katherine B Sulka, Machlan Sawden, Kimberly A Carroll, Ronald D Brown, Stephen C Bunnell, Alexander Poltorak, Albert Tai, Eric R Reed, Shruti Sharma.

Local immune processes within aging tissues are a significant driver of aging associated dysfunction, but tissue-autonomous pathways and cell types that modulate these responses remain poorly characterized. The cytosolic DNA sensing pathway, acting through cyclic GMP-AMP synthase (cGAS) and Stimulator of Interferon Genes (STING), is broadly expressed in tissues, and is poised to regulate local type I interferon (IFN-I)-dependent and independent inflammatory processes within tissues. Recent studies suggest that the cGAS/STING pathway may drive pathology in various in vitro and in vivo models of accelerated aging. To date, however, the role of the cGAS/STING pathway in physiological aging processes, in the absence of genetic drivers, has remained unexplored. This remains a relevant gap, as STING is ubiquitously expressed, implicated in multitudinous disorders, and loss of function polymorphisms of STING are highly prevalent in the human population (>50%). Here we reveal that, during physiological aging, STING-deficiency leads to a significant shortening of murine lifespan, increased pro-inflammatory serum cytokines and tissue infiltrates, as well as salient changes in histological composition and organization. We note that aging hearts, livers, and kidneys express distinct subsets of inflammatory, interferon-stimulated gene (ISG), and senescence genes, collectively comprising an immune fingerprint for each tissue. These distinctive patterns are largely imprinted by tissue-specific stromal and myeloid cells. Using cellular interaction network analyses, immunofluorescence, and histopathology data, we show that these immune fingerprints shape the tissue architecture and the landscape of cell-cell interactions in aging tissues. These age-associated immune fingerprints are grossly dysregulated with STING-deficiency, with key genes that define aging STING- sufficient tissues greatly diminished in the absence of STING. Changes in immune signatures are concomitant with a restructuring of the stromal and myeloid fractions, whereby cell:cell interactions are grossly altered and resulting in disorganization of tissue architecture in STING-deficient organs. This altered homeostasis in aging STING-deficient tissues is associated with a cross-tissue loss of homeostatic tissue-resident macrophage (TRM) populations in these tissues. Ex vivo analyses reveal that basal STING- signaling limits the susceptibility of TRMs to death-inducing stimuli and determines their in situ localization in tissue niches, thereby promoting tissue homeostasis. Collectively, these data upend the paradigm that cGAS/STING signaling is primarily pathological in aging and instead indicate that basal STING signaling sustains tissue function and supports organismal longevity. Critically, our study urges caution in the indiscriminate targeting of these pathways, which may result in unpredictable and pathological consequences for health during aging.
HIGHLIGHTS: Aging tissues are associated with tissue-autonomous immune fingerprints, primarily driven by interactions of tissue stromal and myeloid populations. STING shapes these immune fingerprints of aging tissues in unexpected ways.Loss of STING alters the location, numbers, and viability of tissue resident macrophages.STING signaling is critical for longer lifespans and maintenance of tissue architecture.

DOI: https://doi.org/10.1101/2024.04.04.588107
Curr Med Chem. 2024 Apr 19.

Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy.

Mariia Shanaida, Roman Lysiuk, Olha Mykhailenko, Nataliia Hudz, Abdullateef Abdulsalam, Tetiana Gontova, Oleksandra Oleshchuk, Yana Ivankiv, Volodymyr Shanaida, Dmytro Lytkin, Geir Bjørklund.

  The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted a growing interest in recent years. αLA is a short- -chain sulfur-containing fatty acid occurring in the mitochondria of all kinds of eukaryotic cells. Both the oxidized disulfide of αLA and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent antioxidant function. The amount of αLA inside the human body gradually decreases with age resulting in various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. The primary objectives of this study were the analysis of updated information on the latest two-decade research regarding the use of αLA from an anti-aging perspective. The information was collected from PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, and clinicaltrials.gov. Numerous in silico, in vitro, in vivo, and clinical studies revealed that αLA shows a protective role in biological systems by direct or indirect reactive oxygen/nitrogen species quenching. αLA demonstrated beneficial properties in the prevention and treatment of many age-related disorders such as neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, and skin senescence. Its preventive effects in case of Alzheimer's and Parkinson's diseases are of particular interest. Further mechanistic and clinical studies are highly recommended to evaluate the wide spectrum of αLA therapeutic potential that could optimize its dietary intake for prevention and alleviation disorders related to aging.

Keywords:  Free radicals; atherosclerosis; cancer; chelating metals; detoxification; diabetes; dosage forms; infertility; nanoformulations.; nephropathy; neurodegeneration; obesity; skin senescence

DOI:  https://doi.org/10.2174/0109298673300496240416114827
Antioxidants (Basel). 2024 Mar 25. pii: 394. [Epub ahead of print]13(4):

Progress in Understanding Oxidative Stress, Aging, and Aging-Related Diseases.

Jianying Yang, Juyue Luo, Xutong Tian, Yaping Zhao, Yumeng Li, Xin Wu.

  Under normal physiological conditions, reactive oxygen species (ROS) are produced through redox reactions as byproducts of respiratory and metabolic activities. However, due to various endogenous and exogenous factors, the body may produce excessive ROS, which leads to oxidative stress (OS). Numerous studies have shown that OS causes a variety of pathological changes in cells, including mitochondrial dysfunction, DNA damage, telomere shortening, lipid peroxidation, and protein oxidative modification, all of which can trigger apoptosis and senescence. OS also induces a variety of aging-related diseases, such as retinal disease, neurodegenerative disease, osteoarthritis, cardiovascular diseases, cancer, ovarian disease, and prostate disease. In this review, we aim to introduce the multiple internal and external triggers that mediate ROS levels in rodents and humans as well as the relationship between OS, aging, and aging-related diseases. Finally, we present a statistical analysis of effective antioxidant measures currently being developed and applied in the field of aging research.

Keywords:  aging; aging-related diseases; antioxidants; reactive oxygen species

DOI:  https://doi.org/10.3390/antiox13040394
Bioresour Bioprocess. 2023 Aug 28. 10(1): 55

Protective effects of Aureobasidium pullulans lysate on UV-damaged human skin fibroblasts and HaCaT cells.

Xin Wang, Yongtao Zhang, Dongdong Wang, Ning Su, Li Yang, Hao Fu, Jiachan Zhang, Meng Li, Changtao Wang.

   BACKGROUND: Aureobasidium pullulans (A. pullulans) has a wide range of applications. Ultraviolet (UV) rays from the sun can cause skin photoaging. In order to explore the protective effect and application potential of A. pullulans lysate on UV-damaged human skin fibroblasts (HSF) and HaCaT Cells, this study investigates the anti-aging and anti-inflammatory effects of A. pullulans lysate as well as the mechanism of anti-oxidative stress at the cellular and molecular levels through cytotoxicity experiments, enzyme-linked immunosorbent assays (ELISA), and real-time quantitative PCR (RT-qPCR).
RESULTS: The experimental results have shown that the A. pullulans lysate can effectively reduce the loss of extracellular matrix components (EMC), such as collagen and hyaluronic acid (HA). It is also capable of scavenging excess reactive oxygen species (ROS) from the body, thereby increasing the activity of catalase, decreasing the overexpression of intracellular matrix metalloproteinases (MMPs), enhancing the gene expression of metalloproteinase inhibitors (TIMPs), and decreasing the level of inflammatory factors, reducing UV-induced apoptosis of HaCaT cells. Meanwhile, oxidative stress homeostasis is also regulated through the Nrf2/Keap1 and MAPK signaling pathways.
CONCLUSIONS: This study shows that the A. pullulans lysate has the potential to resist photoaging.

Keywords:   A. pullulans lysate; Human immortalized keratinocytes; Human skin fibroblasts; UV

DOI:  https://doi.org/10.1186/s40643-023-00678-9
Front Med Technol. 2024 ;6 1384648

Reprogramming T cells as an emerging treatment to slow human age-related decline in health.

Philip V Peplow.



Keywords:  age-related decline; health; human; reprogramming T cells; treatment

DOI:  https://doi.org/10.3389/fmedt.2024.1384648
Proc Natl Acad Sci U S A. 2024 Apr 30. 121(18): e2311028121

Senolytic and senomorphic agent procyanidin C1 alleviates structural and functional decline in the aged retina.

Yidan Liu, Xiuxing Liu, Xuhao Chen, Zhenlan Yang, Jianqi Chen, Weining Zhu, Yangyang Li, Yuwen Wen, Caibin Deng, Chenyang Gu, Jianjie Lv, Rong Ju, Yehong Zhuo, Wenru Su.

  Increased cellular senescence burden contributes in part to age-related organ dysfunction and pathologies. In our study, using mouse models of natural aging, we observed structural and functional decline in the aged retina, which was accompanied by the accumulation of senescent cells and senescence-associated secretory phenotype factors. We further validated the senolytic and senomorphic properties of procyanidin C1 (PCC1) both in vitro and in vivo, the long-term treatment of which ameliorated age-related retinal impairment. Through high-throughput single-cell RNA sequencing (scRNA-seq), we comprehensively characterized the retinal landscape after PCC1 administration and deciphered the molecular basis underlying the senescence burden increment and elimination. By exploring the scRNA-seq database of age-related retinal disorders, we revealed the role of cellular senescence and the therapeutic potential of PCC1 in these pathologies. Overall, these results indicate the therapeutic effects of PCC1 on the aged retina and its potential use for treating age-related retinal disorders.

Keywords:  aging; cellular senescence; retina; senescence-associated secretory phenotype; senolytics

DOI:  https://doi.org/10.1073/pnas.2311028121
Tissue Eng Regen Med. 2024 Apr 22.

Hyaluronic Acid Based Adipose Tissue-Derived Extracellular Matrix Scaffold in Wound Healing: Histological and Immunohistochemical Study.

Dong Yeon Kim, Eunjeong Ko, Yeon Hee Ryu, Su Jin Lee, Young Joon Jun.

   BACKGROUND: In this study, we explored the potential of human adipose tissue-derived extracellular matrix (adECM) sheets augmented with crosslinked hyaluronic acid (HA) as advanced wound dressings. We aimed to enhance healing efficacy while optimizing cost efficiency.
METHODS: The adECM was processed from healthy donor tissue and combined with crosslinked HA to form ECM-HA sheets (Scaffiller, Medikan, Korea). In vitro experiments involved seeding adipose-derived stem cells (ASCs) onto these sheets and assessing cell survival and cytokine production. In vivo testing utilized a rat wound model, comparing ECM-HA sheet with HA-based dressing and polyurethane foam dressing. Re-epithelialization and collagen deposition were examined through histopathological examinations, whereas immunohistochemistry was used to assess CD31, alpha smooth muscle actin (α-SMA), and Tenascin C expression as contributing factors to wound healing.
RESULTS: Results indicated that ECM-HA sheets were produced efficiently, with enhanced growth factor production and ASC survival observed in vitro. In vivo, ECM-HA sheets demonstrated accelerated wound healing, evidenced by improved epithelialization, thicker dermis, increased collagen deposition, and enhanced vascularity. Notably, they exhibited reduced myofibroblast activity and increased expression of Tenascin C, suggesting a favorable healing environment.
CONCLUSION: ECM-HA sheets offer a promising approach for wound management, combining the benefits of adECM and HA. They present improved stability and cost-effectiveness while promoting essential aspects of wound healing such as angiogenesis and collagen formation. This study underscores the therapeutic potential of ECM-HA sheets in clinical applications aimed at facilitating wound repair.

Keywords:  Adipose tissue; Extracellular matrix; Hyaluronic acid; Scaffold; Wound healing

DOI:  https://doi.org/10.1007/s13770-024-00644-2
CNS Neurol Disord Drug Targets. 2024 ;23(5): 543-544

Food, Dietary Supplements and Nutraceuticals in Aging and Neurodegenerative Diseases.

Fabiola De Marchi, Giacomo Tondo.

DOI: https://doi.org/10.2174/187152732305231202011902
Immunol Cell Biol. 2024 Apr 22.

Highlight of 2023: Unraveling the complexity of T cell aging - insights from recent advances.

Jing Guo, Zhonghui Xue, Lie Wang.

  Unraveling the complexities of T cell aging is essential for developing targeted interventions to enhance immune function in the elderly. This article for the Highlights of 2023 Series integrates recent findings published in 2023, offering a panoramic view of the current understanding of T cell aging and its implications.

Keywords:  CD4+ T cells; CD8+ T cells; Immunosenescence; T cell aging

DOI:  https://doi.org/10.1111/imcb.12755
Biomolecules. 2024 Apr 09. pii: 459. [Epub ahead of print]14(4):

Applications of Exosomal miRNAs from Mesenchymal Stem Cells as Skin Boosters.

Jinmei Zheng, Beibei Yang, Siqi Liu, Zhenfeng Xu, Zhimeng Ding, Miaohua Mo.

  The skin is the outer layer of the human body, and it is crucial in defending against injuries and damage. The regenerative capacity of aging and damaged skin caused by exposure to external stimuli is significantly impaired. Currently, the rise in average life expectancy and the modern population's aesthetic standards have sparked a desire for stem-cell-based therapies that can address skin health conditions. In recent years, mesenchymal stem cells (MSCs) as therapeutic agents have provided a promising and effective alternative for managing skin regeneration and rejuvenation, attributing to their healing capacities that can be applied to damaged and aged skin. However, it has been established that the therapeutic effects of MSC may be primarily mediated by paracrine mechanisms, particularly the release of exosomes (Exos). Exosomes are nanoscale extracellular vesicles (EVs) that have lipid bilayer and membrane structures and can be naturally released by different types of cells. They influence the physiological and pathological processes of recipient cells by transferring a variety of bioactive molecules, including lipids, proteins, and nucleic acids such as messenger RNAs (mRNAs) and microRNAs (miRNAs) between cells, thus playing an important role in intercellular communication and activating signaling pathways in target cells. Among them, miRNAs, a type of endogenous regulatory non-coding RNA, are often incorporated into exosomes as important signaling molecules regulating protein biosynthesis. Emerging evidence suggests that exosomal miRNAs from MSC play a key role in skin regeneration and rejuvenation by targeting multiple genes and regulating various biological processes, such as participating in inflammatory responses, cell migration, proliferation, and apoptosis. In this review, we summarize the recent studies and observations on how MSC-derived exosomal miRNAs contribute to the regeneration and rejuvenation of skin tissue, with particular attention to the applications of bioengineering methods for manipulating the miRNA content of exosome cargo to improve their therapeutic potential. This review can provide new clues for the diagnosis and treatment of skin damage and aging, as well as assist investigators in exploring innovative therapeutic strategies for treating a multitude of skin problems with the aim of delaying skin aging, promoting skin regeneration, and maintaining healthy skin.

Keywords:  bioengineering approaches; exosomes; mesenchymal stem cells; miRNAs; skin regeneration and rejuvenation

DOI:  https://doi.org/10.3390/biom14040459
Skin Res Technol. 2024 Apr;30(4): e13714

Use of platelet rich plasma for skin rejuvenation.

Lam Kar Wai Phoebe, Kar Wai Alvin Lee, Lisa Kwin Wah Chan, Lee Cheuk Hung, Raymond Wu, Sky Wong, Jovian Wan, Kyu-Ho Yi.

   OBJECTIVE: Platelet-rich plasma (PRP) is recognized as a safe and effective therapy for regenerative skin healing and rejuvenation, utilizing autologous blood enriched with various growth factors. This review aims to assess the efficacy of PRP treatments for skin rejuvenation.
METHODS: Keywords such as "platelet-rich plasma," "rejuvenation," "skin aging," and "wrinkles" were queried on Ovid, PubMed, and MEDLINE to identify pertinent studies on PRP treatment for skin rejuvenation.
RESULTS: Analysis revealed that PRP treatment led to significant enhancements in multiple facial parameters after one to three sessions. Improvements were noted in skin pore size, texture, wrinkle reduction, pigmented spots, collagen density, hyaluronic acid levels, and protection against ultraviolet damage. Combining PRP with hyaluronic acid demonstrated a synergistic effect, particularly enhancing skin elasticity in patients with lower body mass index and firmness in individuals aged 50s and 60s. Incorporating both physical and biometric data for assessment proved superior to relying solely on physical observations for evaluating subtle skin quality and structural changes.
CONCLUSION: This study underscores the efficacy of PRP monotherapy for skin rejuvenation and emphasizes the necessity of standardizing PRP preparation protocols in future investigations. Heightened awareness and advancements in technology have contributed to the emergence of higher-quality, less biased studies supporting PRP as a reliable and safe therapeutic option for skin rejuvenation.

Keywords:  cell‐ and tissue‐based therapy; platelet‐rich plasma; rejuvenation; skin aging; wrinkling

DOI:  https://doi.org/10.1111/srt.13714