bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2024–12–22
33 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Telomerase-Mediated Anti-Ageing Interventions.
  2. The Role of Calorie Restriction in Modifying the Ageing Process through the Regulation of SIRT1 Expression.
  3. A Binary siRNA-Loaded Tetrahedral DNA Nanobox for Synergetic Anti-Aging Therapy.
  4. Rejuvenating aged osteoprogenitors for bone repair.
  5. Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors.
  6. Stem Cell Therapies and Ageing: Unlocking the Potential of Regenerative Medicine.
  7. Unlocking the Potential of Senolytic Compounds: Advancements, Opportunities, and Challenges in Ageing-Related Research.
  8. Anti-Aging Effect of Traditional Plant-Based Food: An Overview.
  9. Lifespan Extension and Motor Function Improvement Effects of Whale Meat Extract in Caenorhabditis elegans.
  10. Multi-omic analysis of biological aging biomarkers in long-term calorie restriction and endurance exercise practitioners: A cross-sectional study.
  11. Anti-aging properties of the aminosterols of the dogfish shark.
  12. Chaperone-mediated autophagy as a modulator of aging and longevity.
  13. Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Strategy for Age-Related Diseases.
  14. Inter- and intracellular mitochondrial communication: signaling hubs in aging and age-related diseases.
  15. NAD+ Boosting Strategies.
  16. [Astragalus polysaccharides improve adipose tissue aging in naturally aged mice via indole-3-lactic acid].
  17. Research of in vivo reprogramming toward clinical applications in regenerative medicine: A concise review.
  18. Partial Reprogramming Exerts a Rejuvenating Effect on Human Mesenchymal Stem Cells That Underwent Replicative Senescence in Culture.
  19. Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies.
  20. A 2-year calorie restriction intervention reduces glycomic biological age biomarkers.
  21. Coniferaldehyde activates autophagy and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans via par-4/aak-2/skn-1 pathway.
  22. Hesperetin Increases Lifespan and Antioxidant Ability Correlating with IIS, HSP, mtUPR, and JNK Pathways of Chronic Oxidative Stress in Caenorhabditis elegans.
  23. Dietary phytochemicals alleviate the premature skin aging: A comprehensive review.
  24. Improved Therapeutic Efficiency of Senescent Cell-specific, Galactose-Functionalized Micelle Nanocarriers.
  25. The muscle stem cell case of Benjamin Button: rejuvenating muscle regenerative capacity through nutraceuticals.
  26. Polygonum multiflorum Extracellular Vesicle-Like Nanovesicle for Skin Photoaging Therapy.
  27. Antioxidant and Antiaging Activity of Houttuynia cordata Thunb. Ethyl Acetate Fraction in Caenorhabditis elegans.
  28. Spatial transcriptomic clocks reveal cell proximity effects in brain ageing.
  29. Resveratrol and Its Analogues: Anti-ageing Effects and Underlying Mechanisms.
  30. Broccoli Sprout Extract Suppresses Particulate-Matter-Induced Matrix-Metalloproteinase (MMP)-1 and Cyclooxygenase (COX)-2 Expression in Human Keratinocytes by Direct Targeting of p38 MAP Kinase.
  31. Lithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing.
  32. Role of Vitamin B in Healthy Ageing and Disease.
  33. Proteasome Activators and Ageing: Restoring Proteostasis Using Small Molecules.
  1. Subcell Biochem. 2024 ;107 1-20
    Telomerase-Mediated Anti-Ageing Interventions.
    Phoebe L Dunn, Dhenugen Logeswaran, Julian J-L Chen.
      The ageing process involves a gradual decline of chromosome integrity throughout an organism's lifespan. Telomeres are protective DNA-protein complexes that cap the ends of linear chromosomes in eukaryotic organisms. Telomeric DNA consists of long stretches of short "TTAGGG" repeats that are conserved across most eukaryotes including humans. Telomeres shorten progressively with each round of DNA replication due to the inability of conventional DNA polymerase to completely replicate the chromosome ends, known as the "end-replication problem". The telomerase enzyme counteracts the telomeric DNA loss by de novo addition of telomeric repeats onto chromosomal ends. Germline and stem cells maintain significant levels of telomerase activity to maintain telomere length and can divide almost indefinitely. However, the differentiation of stem cells accompanies the inactivation of telomerase gene expression, resulting in the progressive shortening of telomeres in somatic cells over successive divisions. Critically short telomeres elicit and sustain a persistent DNA damage response leading to permanent growth arrest of cells known as cellular senescence, a hallmark of cellular ageing. The accumulation of senescent cells in tissues and organs contributes to organismal ageing. Thus, the prevention of telomere shortening is a promising means to delay or even reverse cellular ageing. In this chapter, we summarize potential anti-ageing interventions that mitigate telomere shortening through increasing telomerase level or activity and discuss these strategies' risks, benefits, and future outlooks.
    Keywords:  Cell senescence; DNA replication; End replication problem; Hayflick limit; Ribonucleoprotein; Telomerase activation; Telomere shortening
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_1
  2. Subcell Biochem. 2024 ;107 173-181
    The Role of Calorie Restriction in Modifying the Ageing Process through the Regulation of SIRT1 Expression.
    Monia Kittana, Vasso Apostolopoulos, Lily Stojanovska.
      Calorie restriction (CR), as a dietary approach of reducing caloric intake while maintaining nutritional adequacy, has gained significant attention due to its potential role in promoting longevity and enhancing health. Central to the beneficial effects of CR is SIRT1. SIRT1 belongs to a family of NAD+ dependent deacetylases and plays an important role in regulating various cellular processes, including histone deacetylation, oxidative stress response, and mitochondrial biogenesis. This chapter reviews the evidence regarding the effect of CR on SIRT1 expression and mitochondrial biogenesis. Both pre-clinical and human studies have consistently demonstrated that CR promotes an increase in SIRT1 expression and activity in different tissues. This is also associated with other favourable health outcomes, such as delayed neurodegeneration and improved cognitive function. Moderate CR (25% restriction) has shown an impact on promoting mitochondrial biogenesis, reflected in markers such as mitochondrial DNA and transcription factors. However, this is reviewed in light of some methodological limitations, as data varied in response to different CR regimens. Herein, we highlight the potential of CR in up-regulating SIRT1 and promoting mitochondrial biogenesis, which can have significant implications for developing strategies to manage and promote healthy ageing.
    Keywords:  Ageing; Aging; Calorie restriction; Healthy ageing; Mitochondrial biogenesis; SIRT1; Sirtuins
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_8
  3. Small. 2024 Dec 17. e2408323
    A Binary siRNA-Loaded Tetrahedral DNA Nanobox for Synergetic Anti-Aging Therapy.
    Ziqi Yue, Yichen Yang, Lulingxiao Nie, Yuezhang Sun, Qi Wang, Yunfeng Lin, Yang Gao, Xiaoxiao Cai.
      Extensive accumulation of senescent cells contributes to organismal aging, and slowing down the process of cellular senescence may ameliorate age-related pathologies. Targeted inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) is found to suppress the conversion of cells to senescence. The regulatory-associated protein of mTOR (Raptor), a key component of mTORC1, has been implicated as important in the aging process, and its druggability deserves to be investigated. Due to high efficiency and high convenience in drug construction, siRNA shows great potential in silencing Raptor expression via RNA interfering therapy. Here, we developed a functionalized anti-aging nanoplatform based on tetrahedral DNA nanostructures (TDNs) encapsulating siRNA targeting Raptor for synergistic anti-aging therapy, named siR-TDNbox. Anti-inflammatory and antioxidant properties of TDN beneficially attenuate age-associated inflammation while serving as siRNA nanocarrier, and thus play a binary role. The results suggest that the siR-TDNbox binary therapeutic nanoplatform has demonstrated an excellent ability to delay aging, inhibit mTORC1 signaling, and extend lifespan. This anti-aging nanoplatform may provide a medium for the combined application of traditional senotherapeutic drugs and promote the upgrading of nanomaterials with anti-aging effects.
    Keywords:  DNA nanotechnology; aging; framework nucleic acids; senescence; siRNA delivery
    DOI:  https://doi.org/10.1002/smll.202408323
  4. Elife. 2024 Dec 18. pii: RP104068. [Epub ahead of print]13
    Rejuvenating aged osteoprogenitors for bone repair.
    Joshua Reeves, Pierre Tournier, Pierre Becquart, Robert Carton, Yin Tang, Alessandra Vigilante, Dong Fang, Shukry J Habib.
      Aging is marked by a decline in tissue regeneration, posing significant challenges to an increasingly older population. Here, we investigate age-related impairments in calvarial bone healing and introduce a novel two-part rejuvenation strategy to restore youthful repair. We demonstrate that aging negatively impacts the calvarial bone structure and its osteogenic tissues, diminishing osteoprogenitor number and function and severely impairing bone formation. Notably, increasing osteogenic cell numbers locally fails to rescue repair in aged mice, identifying the presence of intrinsic cellular deficits. Our strategy combines Wnt-mediated osteoprogenitor expansion with intermittent fasting, which leads to a striking restoration of youthful levels of bone healing. We find that intermittent fasting improves osteoprogenitor function, benefits that can be recapitulated by modulating NAD+-dependent pathways or the gut microbiota, underscoring the multifaceted nature of this intervention. Mechanistically, we identify mitochondrial dysfunction as a key component in age-related decline in osteoprogenitor function and show that both cyclical nutrient deprivation and Nicotinamide mononucleotide rejuvenate mitochondrial health, enhancing osteogenesis. These findings offer a promising therapeutic avenue for restoring youthful bone repair in aged individuals, with potential implications for rejuvenating other tissues.
    Keywords:  Wnt; aging; bone; intermittent fasting; mouse; osteoprogenitors; regenerative medicine; rejuvenation; stem cells
    DOI:  https://doi.org/10.7554/eLife.104068
  5. Cell Commun Signal. 2024 Dec 18. 22(1): 609
    Targeting cellular senescence in kidney diseases and aging: A focus on mesenchymal stem cells and their paracrine factors.
    Seyyedeh Mina Hejazian, Seyyed Sina Hejazian, Seyyedeh Mina Mostafavi, Seyed Mahdi Hosseiniyan, Soheila Montazersaheb, Mohammadreza Ardalan, Sepideh Zununi Vahed, Abolfazl Barzegari.
      Cellular senescence is a phenomenon distinguished by the halting of cellular division, typically triggered by DNA injury or numerous stress-inducing factors. Cellular senescence is implicated in various pathological and physiological processes and is a hallmark of aging. The presence of accumulated senescent cells, whether transiently (acute senescence) or persistently (chronic senescence) plays a dual role in various conditions such as natural kidney aging and different kidney disorders. Elevations in senescent cells and senescence-associated secretory phenotype (SASP) levels correlate with decreased kidney function, kidney ailments, and age-related conditions. Strategies involving senotherapeutic agents like senolytics, senomorphics, and senoinflammation have been devised to specifically target senescent cells. Mesenchymal stem cells (MSCs) and their secreted factors may also offer alternative approaches for anti-senescence interventions. The MSC-derived secretome compromises significant therapeutic benefits in kidney diseases by facilitating tissue repair via anti-inflammatory, anti-fibrosis, anti-apoptotic, and pro-angiogenesis effects, thereby improving kidney function and mitigating disease progression. Moreover, by promoting the clearance of senescent cells or modulating their secretory profiles, MSCs could potentially reverse some age-related declines in kidney function.This review article intends to shed light on the present discoveries concerning the role of cellular senescence in kidney aging and diseases. Furthermore, it outlines the role of senotherapeutics utilized to alleviate kidney damage and aging. It also highlights the possible impact of MSCs secretome on mitigating kidney injury and prolonging lifespan across various models of kidney diseases as a novel senotherapy.
    Keywords:  Acute kidney injury; Cellular senescence; Chronic kidney disease; Kidney aging; Mesenchymal stem cells; Secretome of MSCs
    DOI:  https://doi.org/10.1186/s12964-024-01968-1
  6. Subcell Biochem. 2024 ;107 117-128
    Stem Cell Therapies and Ageing: Unlocking the Potential of Regenerative Medicine.
    Chen Rui, Mike K S Chan, Thomas Skutella.
      A multifaceted biological process of ageing culminates in the gradual decline of tissue and organ functions, escalating vulnerability to age-related diseases. Stem cell therapies, standing at the frontier of regenerative medicine, hold the potential to mitigate the challenges induced by ageing. By harnessing the unique regenerative capabilities of stem cells, these therapies aim to renew and heal ageing or damaged cells and tissues, thereby bolstering their function. In this chapter, we explore the potential of stem cell-based interventions against age-related degeneration, emphasising their underlying mechanisms, challenges, and future possibilities. As elucidated by the Buck Institute for Research on Aging, ageing is characterised by an accrual of macromolecular damage, genomic instability, and loss of heterochromatin (Campisi et al. Nature 571:183-192, 2019). These aspects culminate in stem cell fatigue and a dwindling tissue regenerative capacity. However, with the advent of stem cell therapy and regenerative medicine, we now hold the tools to reverse these age-induced changes by rejuvenating stem cells, the keystones of tissue regeneration, and fostering their proliferation and differentiation.
    Keywords:  Age-related diseases; Ageing; Genomic instability; Regeneration; Stem cells
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_6
  7. Subcell Biochem. 2024 ;107 91-116
    Unlocking the Potential of Senolytic Compounds: Advancements, Opportunities, and Challenges in Ageing-Related Research.
    Lilian Sales Gomez, Diana Jurk.
      Cellular senescence is recognised as a contributor to the ageing process and the development of multiple age-related conditions. Researchers have launched efforts to identify compounds capable to selectively kill senescent cells, known as senolytics, without affecting non senescent cells. As of now, over 40 compounds have demonstrated senolytic properties, offering promising prospects for reversing or ameliorating age-related conditions in preclinical studies.This chapter presents the most recent developments in senolytic drug research, encompassing investigations spanning basic science, preclinical trials, and clinical studies. While many of these investigations have generated encouraging results in the realm of age-related interventions, this chapter also addresses potential challenges and pitfalls.
    Keywords:  Age-related diseases; Ageing; Cellular senescence; Senolytic
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_5
  8. Foods. 2024 Nov 25. pii: 3785. [Epub ahead of print]13(23):
    Anti-Aging Effect of Traditional Plant-Based Food: An Overview.
    Gitishree Das, Srinivasan Kameswaran, Bellamkonda Ramesh, Manjunatha Bangeppagari, Rajat Nath, Anupam Das Talukdar, Han-Seung Shin, Jayanta Kumar Patra.
      Aging is a complex process that involves many physiological mechanisms that gradually impair normal cellular and tissue function and make us more susceptible to diseases and death. It is influenced by intrinsic factors like cellular function and extrinsic factors like pollution and UV radiation. Recent scientific studies show that traditional plant-based foods and supplements can help mitigate the effects of aging. Nutraceuticals, which are dietary supplements with medicinal properties, have gained attention for their ability to prevent chronic and age-related diseases. Antioxidants like flavonoids, carotenoids, ascorbic acid, terpenes, tannins, saponins, alkaloids, minerals, etc. found in plants are key to managing oxidative stress, which is a major cause of aging. Well-known plant-based supplements from Bacopa monnieri, Curcuma longa, Emblica officinalis, Ginkgo biloba, Glycyrrhiza glabra, and Panax ginseng have been found to possess medicinal properties. These supplements have been shown to improve cognitive function, reduce oxidative stress, improve overall health, and potentially extend life and enhance the excellence of life. The obtained benefits from these plant species are due to the presence of their bioactive secondary metabolites, such as bacosides in Bacopa monnieri, curcumin in Curcuma longa, ginsenosides in Panax ginseng, and many more. These compounds not only protect against free radical damage but also modulate key biological pathways of aging. Also, traditional fermented foods (tempeh and kimchi), which are rich in probiotics and bioactive compounds, support gut health, boost immune function, and have anti-aging properties. The molecular mechanisms behind these benefits are the activation of nutrient-sensing pathways like AMPK, SIRT/NAD+, and mTOR, which are important for cellular homeostasis and longevity. This review shows the potential of traditional plant-based foods and dietary supplements for healthy aging, and more studies are needed to prove their efficacy and safety in humans. Incorporating these natural products into our diet may be a practical and effective way to counteract the effects of aging and overall well-being. The foremost goal of this review is to emphasize the importance of supporting the body's antioxidant system by consuming the right balance of natural ingredients in the diet.
    Keywords:  aging; antioxidants; nutraceuticals; oxidative stress; plant-based supplements
    DOI:  https://doi.org/10.3390/foods13233785
  9. Int J Mol Sci. 2024 Nov 28. pii: 12833. [Epub ahead of print]25(23):
    Lifespan Extension and Motor Function Improvement Effects of Whale Meat Extract in Caenorhabditis elegans.
    Junko Shibato, Fumiko Takenoya, Ai Kimura, Michio Yamashita, Randeep Rakwal, Seiji Shioda.
      The average life expectancy is increasing worldwide, but the same cannot be said for a healthy life expectancy (defined as the period during which a person can live a healthy and independent life). Therefore, a major challenge is how to extend healthy life expectancy. One option is to reduce age-related muscle atrophy (sarcopenia) and cognitive decline. Since there is no specific cure for frailty, the prevention of frailty based on nutrition and exercise is a new approach to achieve healthy longevity. Studies have shown that interventions combining nutritional supplements and exercise are effective in improving muscle strength, muscle mass, and walking speed. Thus, the search for drugs and functional foods to combat frailty has attracted researchers' attention. Whale meat extract (WME) contains many imidazole dipeptides, especially the unique component balenine, which has various functional anti-fatigue and antioxidant properties, and hypermobility effects. Here, we investigated the effects of WME on the aging and health of Caenorhabditis elegans (hereafter, C. elegans). mRNA expression analysis showed that WME prolongs the lifespan of C. elegans mainly through sir-2.1, daf-2, and daf-16, and the myo-3, unc-54, unc-22, and fhod-1 genes involved in locomotor function. The results of this study showed that the expression of the antioxidant enzymes sod-2 and sod-3 was also increased. This study may provide the basis for further research on WME as a food and supplement to slow aging and improve motor function.
    Keywords:  C. elegans; cell culture; gene expression; imidazole peptide; lifespan; whale meat extract
    DOI:  https://doi.org/10.3390/ijms252312833
  10. Aging Cell. 2024 Dec 18. e14442
    Multi-omic analysis of biological aging biomarkers in long-term calorie restriction and endurance exercise practitioners: A cross-sectional study.
    Giovanni Fiorito, Valeria Tosti, Silvia Polidoro, Beatrice Bertozzi, Nicola Veronese, Edda Cava, Francesco Spelta, Laura Piccio, Dayna S Early, Daniel Raftery, Paolo Vineis, Luigi Fontana.
      Calorie restriction (CR) and physical exercise (EX) are well-established interventions known to extend health span and lifespan in animal models. However, their impact on human biological aging remains unclear. With recent advances in omics technologies and biological age (BioAge) metrics, it is now possible to assess the impact of these lifestyle interventions without the need for long-term follow-up. This study compared BioAge biomarkers in 41 middle-aged and older adult long-term CR practitioners, 41 age- and sex-matched endurance athletes (EX), and 35 sedentary controls consuming Western diets (WD), through PhenoAge: a composite score derived from nine blood-biomarkers. Additionally, a subset of participants (12 CR, 11 EX, and 12 WD) underwent multi-omic profiling, including DNA methylation and RNAseq of colon mucosa, blood metabolomics, and stool metagenomics. A group of six young WD subjects (yWD) served as a reference for BioAge calculation using Mahalanobis distance across six omic layers. The results demonstrated consistently lower BioAge biomarkers in both CR and EX groups compared to WD controls across all layers. CR participants exhibited lower BioAge in gut microbiome and blood-derived omics, while EX participants had lower BioAge in colon mucosa-derived epigenetic and transcriptomic markers, suggesting potential tissue-specific effects. Multi-omic pathway enrichment analyses suggested both shared and intervention-specific mechanisms, including oxidative stress and basal transcription as common pathways, with ether lipid metabolism uniquely enriched in CR. Despite limitations due to sample size, these findings contribute to the broader understanding of the potential anti-aging effects of CR and EX, offering promising directions for further research.
    Keywords:  biological aging; calorie restriction; multi‐omic; oxidative stress; physical exercise
    DOI:  https://doi.org/10.1111/acel.14442
  11. NPJ Aging. 2024 Dec 19. 10(1): 62
    Anti-aging properties of the aminosterols of the dogfish shark.
    Denise Barbut, Michele Perni, Michael Zasloff.
      The development of anti-aging drugs is challenged by both the apparent complexity of the physiological mechanisms involved in aging and the likelihood that many of these mechanisms remain unknown. As a consequence, the development of anti-aging compounds based on the rational targeting of specific pathways has fallen short of the goal. To date, the most impressive compound is rapamycin, a natural bacterial product initially identified as an antifungal, and only subsequently discovered to have anti-aging properties. In this review, we focus on two aminosterols from the dogfish shark, Squalus acanthias, that we discovered initially as broad-spectrum anti-microbial agents. This review is the first to gather together published studies conducted both in vitro and in numerous vertebrate species to demonstrate that these compounds target aging pathways at the cellular level and provide benefits in multiple aging-associated conditions in relevant animal models and in humans. The dogfish aminosterols should be recognized as potential anti-aging drugs.
    DOI:  https://doi.org/10.1038/s41514-024-00188-8
  12. Front Aging. 2024 ;5 1509400
    Chaperone-mediated autophagy as a modulator of aging and longevity.
    S Joseph Endicott.
      Chaperone-mediated autophagy (CMA) is the lysosomal degradation of individually selected proteins, independent of vesicle fusion. CMA is a central part of the proteostasis network in vertebrate cells. However, CMA is also a negative regulator of anabolism, and it degrades enzymes required for glycolysis, de novo lipogenesis, and translation at the cytoplasmic ribosome. Recently, CMA has gained attention as a possible modulator of rodent aging. Two mechanistic models have been proposed to explain the relationship between CMA and aging in mice. Both of these models are backed by experimental data, and they are not mutually exclusionary. Model 1, the "Longevity Model," states that lifespan-extending interventions that decrease signaling through the INS/IGF1 signaling axis also increase CMA, which degrades (and thereby reduces the abundance of) several proteins that negatively regulate vertebrate lifespan, such as MYC, NLRP3, ACLY, and ACSS2. Therefore, enhanced CMA, in early and midlife, is hypothesized to slow the aging process. Model 2, the "Aging Model," states that changes in lysosomal membrane dynamics with age lead to age-related losses in the essential CMA component LAMP2A, which in turn reduces CMA, contributes to age-related proteostasis collapse, and leads to overaccumulation of proteins that contribute to age-related diseases, such as Alzheimer's disease, Parkinson's disease, cancer, atherosclerosis, and sterile inflammation. The objective of this review paper is to comprehensively describe the data in support of both of these explanatory models, and to discuss the strengths and limitations of each.
    Keywords:  aging; autophagy; chaperone-mediated autophagy; longevity; metabolism
    DOI:  https://doi.org/10.3389/fragi.2024.1509400
  13. Cell Prolif. 2024 Dec 20. e13795
    Mesenchymal Stem Cell-Derived Exosomes: A Promising Therapeutic Strategy for Age-Related Diseases.
    Bohua Wei, Mengting Wei, Haonan Huang, Ting Fan, Zhichang Zhang, Xiaoyu Song.
      The global increase in the aging population has led to a concurrent rise in the incidence of age-related diseases, posing substantial challenges to healthcare systems and affecting the well-being of the elderly. Identifying and securing effective treatments has become an urgent priority. In this context, mesenchymal stem cell-derived exosomes (MSC-Exos) have emerged as a promising and innovative modality in the field of anti-aging medicine, offering a multifaceted therapeutic approach. MSC-Exos demonstrate significant potential due to their immunomodulatory and anti-inflammatory properties, their ability to inhibit oxidative stress, and their reparative effects on senescent tissues. These attributes make them valuable in combating a range of conditions associated with aging, such as cardiovascular diseases, neurodegeneration, skin aging, and osteoarthritis. The integration of exosomes with membrane-penetrating peptides introduces a novel strategy for the delivery of biomolecules, surmounting traditional cellular barriers and enhancing therapeutic efficacy. This review provides a comprehensive synthesis of the current understanding of MSC-Exos, underscoring their role as a novel and potent therapeutic strategy against the intricate challenges of age-related diseases.
    Keywords:  exosome; immunomodulatory; mesenchymal stem cell; senescence; tissue regeneration
    DOI:  https://doi.org/10.1111/cpr.13795
  14. Cell Mol Biol Lett. 2024 Dec 18. 29(1): 153
    Inter- and intracellular mitochondrial communication: signaling hubs in aging and age-related diseases.
    Meng Zhang, Jin Wei, Chang He, Liutao Sui, Chucheng Jiao, Xiaoyan Zhu, Xudong Pan.
      Mitochondria are versatile and complex organelles that can continuously communicate and interact with the cellular milieu. Deregulated communication between mitochondria and host cells/organelles has significant consequences and is an underlying factor of many pathophysiological conditions, including the process of aging. During aging, mitochondria lose function, and mitocellular communication pathways break down; mitochondrial dysfunction interacts with mitochondrial dyscommunication, forming a vicious circle. Therefore, strategies to protect mitochondrial function and promote effective communication of mitochondria can increase healthy lifespan and longevity, which might be a new treatment paradigm for age-related disorders. In this review, we comprehensively discuss the signal transduction mechanisms of inter- and intracellular mitochondrial communication, as well as the interactions between mitochondrial communication and the hallmarks of aging. This review emphasizes the indispensable position of inter- and intracellular mitochondrial communication in the aging process of organisms, which is crucial as the cellular signaling hubs. In addition, we also specifically focus on the status of mitochondria-targeted interventions to provide potential therapeutic targets for age-related diseases.
    Keywords:  Age-related diseases; Aging; Mitochondrial communication; Mitochondrial dysfunction; Signaling hubs
    DOI:  https://doi.org/10.1186/s11658-024-00669-4
  15. Subcell Biochem. 2024 ;107 63-90
    NAD+ Boosting Strategies.
    Jared Rice, Sofie Lautrup, Evandro F Fang.
      Nicotinamide adenine dinucleotide (oxidized form, NAD+) serves as a co-substrate and co-enzyme in cells to execute its key roles in cell signalling pathways and energetic metabolism, arbitrating cell survival and death. It was discovered in 1906 by Arthur Harden and William John Young in yeast extract which could accelerate alcohol fermentation. NAD acts as an electron acceptor and cofactor throughout the processes of glycolysis, Tricarboxylic Acid Cycle (TCA), β oxidation, and oxidative phosphorylation (OXPHOS). NAD has two forms: NAD+ and NADH. NAD+ is the oxidising coenzyme that is reduced when it picks up electrons. NAD+ levels steadily decline with age, resulting in an increase in vulnerability to chronic illness and perturbed cellular metabolism. Boosting NAD+ levels in various model organisms have resulted in improvements in healthspan and lifespan extension. These results have prompted a search for means by which NAD+ levels in the body can be augmented by both internal and external means. The aim of this chapter is to provide an overview of NAD+, appraise clinical evidence of its importance and success in potentially extending health- and lifespan, as well as to explore NAD+ boosting strategies.
    Keywords:  Ageing; Caloric restriction; NAD+; Neurodegeneration; Nicotinamide mononucleotide; Nicotinamide riboside; Oxidative stress; Supplementation
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_4
  16. Zhongguo Zhong Yao Za Zhi. 2024 Nov;49(22): 5998-6007
    [Astragalus polysaccharides improve adipose tissue aging in naturally aged mice via indole-3-lactic acid].
    Yi-Yang Bao, Ming-Xiao Li, Xin-Xin Gao, Wen-Jing Wei, Wen-Jin Huang, Li-Zhong Lin, Hao Wang, Ning-Ning Zheng, Hou-Kai Li.
      Plant polysaccharides are effective components that widely present in traditional Chinese medicine(TCM), exhibiting rich biological activities. However, as most plant polysaccharides cannot be directly absorbed and utilized by the human digestive system, it is now believed that their mode of action mainly involves interaction with intestinal microbiota, leading to the production of functional small molecules. The efficacy of Astragalus polysaccharide(APS) is extensive, including weight loss, improvement of fatty liver, reduction of blood lipids, and enhancement of insulin sensitivity, which may also be related to the regulation of intestinal microbiota. Adipose tissue senescence is an important characteristic of the physiological aging process in the body, often occurring prior to the aging of other important organs. Its main features include the accumulation of senescent cells and exacerbation of inflammation within the tissue. Therefore, to explore the potential protective effects of APS on aging, the improvement of adipose tissue aging phenotype in naturally aging mice was observed using APS, and combined with metagenomic metabolomics, corresponding microbial metabolic functional molecules were identified. Furthermore, functional tests in cell aging models were conducted. The results showed that APS significantly improved the adipocyte aging characteristics of naturally aging mice: specifically reducing aging-induced adipocyte hypertrophy; decreasing the protein expression of aging markers cyclin-dependent kinase inhibitor p21(P21) and multiple tumor suppressor 1(P16); lowering the tissue inflammation reaction. Metagenomic metabolomic analysis of serum from mice in each group revealed that APS significantly increased the content of indole-3-lactic acid(ILA) in naturally aging mice. Further in vitro studies showed that ILA could improve the aging of 3T3-L1 mouse embryonic fibroblasts induced by bleomycin, reduce the protein expression of the aging marker P21, alleviate inflammation, and enhance the ability of preadipocytes to mature. Therefore, APS had the efficacy of protecting naturally aging mice, and its action may be related to the increase in the intestinal microbiota metabolite ILA. This study suggested that TCM may serve as an important entry point for explaining the mechanism of action of TCM by regulating intestinal microbiota and their functional metabolites.
    Keywords:  Astragalus polysaccharide; aging; indole-3-lactic acid; metabolomics
    DOI:  https://doi.org/10.19540/j.cnki.cjcmm.20240508.401
  17. Regen Ther. 2025 Mar;28 12-19
    Research of in vivo reprogramming toward clinical applications in regenerative medicine: A concise review.
    Yoshihiko Nakatsukasa, Yosuke Yamada, Yasuhiro Yamada.
      The successful generation of induced pluripotent stem cells (iPSCs) has significantly impacted many scientific fields. In the field of regenerative medicine, iPSC-derived somatic cells are expected to recover impaired organ functions through cell transplantation therapy. Subsequent studies using genetically engineered mouse models showed that somatic cells are also reprogrammable in vivo. Notably, cyclic expression of reprogramming factors, so-called partial reprogramming in vivo ameliorates cellular and physiological hallmarks of aging without inducing teratoma formation or premature death of animals. Subsequent studies provided evidence supporting the beneficial effects of partial reprogramming in various organs. Although in vivo reprogramming appears to be a promising strategy for tissue regeneration and rejuvenation, there remain unsolved issues that hinder its clinical application, including concerns regarding its safety, controllability, and unexpected detrimental effects. Here, we review the pathway that research of in vivo reprogramming has followed and discuss the future perspective as we look toward its clinical application in regenerative medicine.
    Keywords:  Induced pluripotent stem cells; In vivo reprogramming; Regeneration; Regenerative medicine; Rejuvenation
    DOI:  https://doi.org/10.1016/j.reth.2024.11.008
  18. Int J Mol Sci. 2024 Nov 22. pii: 12533. [Epub ahead of print]25(23):
    Partial Reprogramming Exerts a Rejuvenating Effect on Human Mesenchymal Stem Cells That Underwent Replicative Senescence in Culture.
    Julia Ivanova, Mariia Shorokhova, Natalia Pugovkina, Irina Kozhukharova, Larisa Alekseenko, Nikita Guriev, Ivan Kuneev, Alisa Domnina, Tatiana Grinchuk, Victoria Zemelko, Olga Lyublinskaya.
      Mesenchymal stem/stromal cells (MSCs) are becoming increasingly important for biomedical applications, such as cell therapy, disease modeling, and drug screening. At the same time, long-term cultivation, which is necessary to prepare a sufficient amount of cellular material for therapeutic and research purposes, is accompanied by the development of replicative senescence. Partial reprogramming emerged as a novel method that shows promising results in the rejuvenation of cells in vitro and in vivo; however, it has not yet been applied for human MSCs that have undergone replicative senescence in culture. In the present study, we subjected senescent human endometrial MSCs to partial reprogramming using Sendai virus vectors containing genes encoding Yamanaka transcription factors Oct4, Sox2, Klf4, and c-Myc. Characterization of the MSCs 5 days after transduction showed the loss of key markers of senescence: the youthful morphology was restored, the expression of senescent-associated β-galactosidase and the number of double-strand DNA breaks decreased, proliferation was activated, and the DNA damage response was enhanced. Further, using an in vitro wound-healing assay, we demonstrated that conditioned medium from partially reprogrammed MSCs showed higher therapeutic activity than that from senescent cells. However, a biosafety test revealed the presence of viral components in conditioned medium, which caused the agglutination of erythrocytes. Collectively, our data suggest that partial reprogramming is a potentially effective strategy for the rejuvenation of cultured MSCs in late passages but requires the use of virus-free protocols, such as chemical reprogramming.
    Keywords:  Sendai virus; Yamanaka factors; mesenchymal stem cells; partial reprogramming; rejuvenation; replicative senescence
    DOI:  https://doi.org/10.3390/ijms252312533
  19. Saudi Pharm J. 2024 Dec;32(12): 102209
    Drug delivery for age-related bone diseases: From therapeutic targets to common and emerging therapeutic strategies.
    Jiaming Bi, Jiawei Zeng, Xiaohao Liu, Chuzi Mo, Mingyan Yao, Jing Zhang, Peiyan Yuan, Bo Jia, Shuaimei Xu.
      With the accumulation of knowledge on aging, people have gradually realized that among the many factors that cause individual aging, the accumulation of aging cells is an essential cause of organ degeneration and, ultimately, age-related diseases. Most cells present in the bone microenvironment gradually age over time, leading to an imbalance of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis. This imbalance contributes to age-related bone loss and the development of age-related bone diseases, such as osteoporosis. Bone aging can prolong the lifespan and delay the development of age-related diseases. Nanoparticles have controllable and stable physical and chemical properties and can precisely target different tissues and organs. By preparing multiple easily modified and biocompatible nanoparticles as different drug delivery carriers, specifically targeting various diseased tissues for controlled-release and sustained-release administration, the delivery efficiency of drugs can be significantly improved, and the toxicity and side effects of drugs can be substantially reduced, thereby improving the therapeutic effect of age-related bone diseases. In addition, other novel anti-aging strategies (such as stem cell exosomes) also have significant scientific and practical significance in anti-aging research on age-related bone diseases. This article reviews the research progress of various nano-drug-loaded particles and emerging anti-aging methods for treating age-related bone diseases, offering new insights and directions for precise targeted clinical therapies.
    Keywords:  Age-related bone diseases; Anti-aging; Cell senescence; Drug delivery; Nanotechnology
    DOI:  https://doi.org/10.1016/j.jsps.2024.102209
  20. medRxiv. 2024 Dec 05. pii: 2024.12.04.24318451. [Epub ahead of print]
    A 2-year calorie restriction intervention reduces glycomic biological age biomarkers.
    Tea Pribić, Jayanta K Das, Lovorka Đerek, Daniel W Belsky, Melissa Orenduff, Kim M Huffman, William E Kraus, Helena Deriš, Jelena Šimunović, Tamara Štambuk, Azra Frkatović Hodžić, Virginia B Kraus, Sai Krupa Das, Susan B Racette, Nirad Banskota, Luigi Ferruci, Carl Pieper, Nathan E Lewis, Gordan Lauc, Sridevi Krishnan.
       Background/Objective: In a subset of participants from the CALERIE™ Phase 2 study we evaluated the effects of 2y of ∼25% Calorie Restriction (CR) diet on IgG N-glycosylation (GlycAge), plasma and complement C3 N-glycome as markers of aging and inflammaging.
    Methods: Plasma samples from 26 participants in the CR group who completed the CALERIE2 trial and were deemed adherent to the intervention (∼>10 % CR at 12 mo) were obtained from the NIA AgingResearchBiobank. Glycomic investigations using UPLC or LC-MS analyses were conducted on samples from baseline (BL), mid-intervention (12 mo) and post-intervention (24 mo), and changes resulting from the 2y CR intervention were examined. In addition, anthropometric, clinical, metabolic, DNA methylation (epigenetic) and skeletal muscle transcriptomic data were analyzed to identify aging-related changes that occurred in tandem with the N-glycome changes.
    Results: Following the 2y CR intervention, IgG galactosylation was higher at 24mo compared to BL (p = 0.051), digalactosylation and GlycAge (the IgG-based surrogate for biological age) were not different between BL and 12mo or BL and 24mo, but increased between 12mo and 24mo (p = 0.016, 0.027 respectively). GlycAge was also positively associated with TNF-α and ICAM-1 (p=0.030, p=0.017 respectively). Plasma highly branched glycans were decreased by the 2y intervention (BL vs 24 mo: p=0.013), but both plasma and IgG bisecting GlcNAcs were increased (BL vs 24mo: p<0.001, p = 0.01 respectively). Furthermore, total complement C3 protein concentrations were reduced (BL vs 24mo: p <0.001), as were Man9 glycoforms (BL vs 24mo: p<0.001), and Man10 (which is glucosylated) C3 glycoforms (BL vs 24mo: p = 0.046).
    Conclusions: 24-mos of CR was associated with several favorable, anti-aging, anti- inflammatory changes in the glycome: increased galactosylation, reduced branching glycans, and reduced GlycAge. These promising CR effects were accompanied by an increase in bisecting GlcNAc, a known pro-inflammatory biomarker. These intriguing findings linking CR, clinical, and glycomic changes may be anti-aging and inflammatory, and merit additional investigation.
    DOI:  https://doi.org/10.1101/2024.12.04.24318451
  21. Biogerontology. 2024 Dec 14. 26(1): 25
    Coniferaldehyde activates autophagy and enhances oxidative stress resistance and lifespan of Caenorhabditis elegans via par-4/aak-2/skn-1 pathway.
    Mahesh Ramatchandirane, Ponsankaran Rajendran, M P Athira, Kitlangki Suchiang.
      Aging represents the gradual accumulation of alterations within an organism over time. The physical and chemical characteristics of our cells gradually change as we age, making it more difficult for our tissues and organs to self-regulate, regenerate, and maintain their structural and functional integrity. AMP- activated protein kinase (AMPK), a well-known sensor of cellular energy status acts as a central regulator of an integrated signalling network that control homeostasis, metabolism, stress resistance, cell survival and autophagy. Coniferaldehyde (CFA), a phenolic compound found in many edible plants, has multiple biological and pharmacological functions. Our findings demonstrated that 50 µM CFA could significantly activate autophagy and reduce oxidative stress, which enhanced the activity of antioxidant enzymes and increased resistance under oxidative stress. CFA treatment could efficiently decrease reactive oxygen species (ROS) levels and positively enhance the expression of antioxidant genes in Caenorhabditis elegans (C. elegans). On the other hand, CFA did not have any role in the lifespan extension of the several mutants linked to the AAK-2/AMPK pathway and it promotes SKN-1 (Skinhead-1) localization into the nucleus, which modulates downstream gene gst-4 (Glutathione S-transferase). In depth investigations revealed that CFA could lower oxidative stress and enhance the lifespan of C. elegans by activating the PAR-4/LKB-1-AAK-2/AMPK-SKN-1/NRF-2 pathway, with crucial involvement of bec-1 and lgg-1 genes for autophagy mediated lifespan extension. This study might contribute to understanding the interactions and mechanisms that allow natural compounds like CFA to treat age-related disorders among several species.
    Keywords:   Caenorhabditis elegans ; par-4/aak-2/skn-1 pathway; Autophagy; Coniferaldehyde; Lifespan; Oxidative stress
    DOI:  https://doi.org/10.1007/s10522-024-10163-1
  22. Int J Mol Sci. 2024 Dec 06. pii: 13148. [Epub ahead of print]25(23):
    Hesperetin Increases Lifespan and Antioxidant Ability Correlating with IIS, HSP, mtUPR, and JNK Pathways of Chronic Oxidative Stress in Caenorhabditis elegans.
    Run-Jia Wang, Ya-Jing Ni, Yan-Qiang Liu.
      Hesperetin (Hst) is a common citrus fruit flavonoid with antioxidant, anti-inflammatory, and anti-neurodegenerative effects. To explore the antioxidant and anti-aging effects and mechanisms of Hst, we induced chronic oxidative stress in Caenorhabditis elegans (C. elegans) using low-concentration H2O2 and examined its effects on lifespan, healthy life index, reactive oxygen species (ROS), antioxidant enzymes, and transcriptomic metrics. Hst significantly prolonged lifespan, increased body bending and pharyngeal pumping frequency, decreased ROS accumulation, and increased antioxidant enzyme activity in normal and stressed C. elegans. Hst significantly upregulated daf-18, daf-16, gst-2, gst-3, gst-4, gst-39, hsp-16.11, sip-1, clpp-1, and dve-1 and downregulated ist-1 and kgb-1 mRNAs in stressed C. elegans. These genes are involved in the insulin/insulin-like growth factor-1 signaling (IIS), heat shock protein (HSP), mitochondrial unfolded protein response (mtUPR), and c-Jun N-terminal kinase (JNK) pathways. In summary, Hst increases lifespan and antioxidant ability, correlating with these pathways, during chronic oxidative stress in C. elegans.
    Keywords:  Caenorhabditis elegans; antioxidative; hesperetin; lifespan; transcriptomic metrics
    DOI:  https://doi.org/10.3390/ijms252313148
  23. Exp Gerontol. 2024 Dec 16. pii: S0531-5565(24)00306-1. [Epub ahead of print] 112660
    Dietary phytochemicals alleviate the premature skin aging: A comprehensive review.
    Harpreet Singh, Y T Kamal, Jessica Pandohee, Arun Kumar Mishra, Aritra Biswas, Sourav Mohanto, Arvind Kumar, Sagnik Nag, Amrita Mishra, Mhaveer Singh, Himanshu Gupta, Hitesh Chopra.
      Skin aging, often called as premature skin aging, is the hastened deterioration of the skin resulting from multiple factors, including UV radiation, environmental contaminants, inadequate nutrition, stress, etc. Dietary phytochemicals, present in fruits, vegetables, and other plant-derived meals, have gained interest due to their efficiency to eradicate free radicals and lowering the release of inflammatory mediators which accounts for premature skin aging. Several dietary phytochemicals, i.e., carotenoids, polyphenols, flavonoids, terpenes, alkaloids, phytosterols, etc., exhibited potential anti-oxidant, anti-inflammatory, suppression of UV damage, and promote collagen synthesis. In addition, dietary phytochemicals include sulfur, present in various foods safeguard the skin against oxidative stress and inflammation. Thus, this article delves into the comprehension of various dietary phytochemicals investigated to alleviate the premature skin aging. The article further highlights specific phytochemicals and their sources, bioavailability, mechanisms, etc., in the context of safeguarding the skin against oxidative stress and inflammation. The present manuscript is a systematic comprehension of the available literature on dietary phytochemicals and skin aging in various database, i.e., PubMed, ScienceDirect, Google Scholar using the keywords, i.e., "dietary phytochemicals", "nutraceuticals", "skin aging" etc., via Boolean operator, i.e., "AND". The dietary guidelines presented in the manuscript is a unique summarization for a broad reader to understand the inclusion of various functional foods, nutrients, supplements, etc., to prevent premature skin aging. Thus, the utilization of dietary phytochemicals has shown a promising avenue in preventing skin aging, however, the future perspectives and challenges of such phytochemicals should be comprehended via clinical investigations.
    Keywords:  Anti-inflammatory; Anti-oxidant; Dietary phytochemicals; Nutraceuticals; Skin aging; Supplements
    DOI:  https://doi.org/10.1016/j.exger.2024.112660
  24. Small. 2024 Dec 18. e2405732
    Improved Therapeutic Efficiency of Senescent Cell-specific, Galactose-Functionalized Micelle Nanocarriers.
    Badri Parshad, Andrew George Baker, Ishtiaq Ahmed, Alejandra Estepa-Fernández, Daniel Muñoz-Espín, Ljiljana Fruk.
      Cellular senescence has recently been recognized as one of the hallmarks of cancer, aging, as well as many age-related disorders, sparking significant interest in the development of senolytics, compounds that can remove senescent cells. However, most current pharmacological strategies face challenges related to non-specific delivery, leading to significant side effects that hinder safe and effective treatments. To address these issues, galactose-functionalized amphiphiles are synthesized that can self-assemble into micelles and be loaded with a senolytic cargo. These galactose-micelles are responsive to the lysosomal β-galactosidase enzyme, present in elevated amounts in senescent cells, and are employed for specific delivery of the senolytic Bcl2-inhibitor Navitoclax. This novel formulation showed reduced delivery and toxicity to non-senescent cells, thereby increasing the senolytic index of Navitoclax and making it suitable for future in vivo experimental designs to improve selectivity and safety profiles.
    Keywords:  amphiphiles; drug delivery; galactose; navitoclax; self‐assembly; senescent cells
    DOI:  https://doi.org/10.1002/smll.202405732
  25. J Clin Invest. 2024 Dec 16. pii: e185054. [Epub ahead of print]134(24):
    The muscle stem cell case of Benjamin Button: rejuvenating muscle regenerative capacity through nutraceuticals.
    Taylor Peach, Mattia Quattrocelli.
      Aging negatively affects the capacity of muscle stem cells (MuSCs) to regenerate muscle. In this issue of the JCI, Ancel, Michaud, and colleagues used a high-content imaging screen to identify nicotinamide and pyridoxine as promoters of MuSC function. The combination of the two compounds promoted MuSC function in vivo in aged mice and in primary cells isolated from older individuals. Furthermore, the two compounds were lower in the circulation of older men, paralleling decreases in lean mass and gait speed. These results advance the translational perspective of rejuvenating MuSC function through nutraceuticals.
    DOI:  https://doi.org/10.1172/JCI185054
  26. Biomater Res. 2024 ;28 0098
    Polygonum multiflorum Extracellular Vesicle-Like Nanovesicle for Skin Photoaging Therapy.
    Junjia He, Luoqin Fu, Yeyu Shen, Yan Teng, Youming Huang, Xiaoxia Ding, Danfeng Xu, Hong Cui, Mingang Zhu, Jiahao Xie, Yue Su, Ting Li, Weitao Huang, Xiaozhou Mou, Qiong Bian, Yibin Fan.
      Ultraviolet (UV) irradiation leads to the degradation of the extracellular matrix and collagen, thereby accelerating skin aging and imposing substantial psychological burden on patients. Current anti-aging strategies are limited and often associated with high costs or strong side effects. Plant-derived extracellular vesicle-like nanovesicles, with advantages such as natural availability and cost-effectiveness, show potential in anti-aging interventions. This study extracted extracellular vesicle-like nanovesicle from Polygonum multiflorum (PMELNVs) and systematically investigated their composition and metabolic pathways, further examining their efficacy and underlying mechanisms in combating photoaging. Results revealed the excellent antioxidative properties of PMELNVs, alleviating UV-induced oxidative stress, inhibiting matrix metalloproteinase production, reducing extracellular matrix degradation, promoting collagen synthesis, and ultimately exerting anti-photoaging effects. Additionally, safety assessments demonstrated favorable biocompatibility of PMELNVs. This study provides novel evidence supporting PMELNVs' ability to resist photoaging by reducing oxidative stress and enhancing collagen expression, thereby offering potential as a new natural therapeutic agent against skin photoaging and promising a safer and more effective local anti-aging strategy.
    DOI:  https://doi.org/10.34133/bmr.0098
  27. Nutrients. 2024 Nov 30. pii: 4168. [Epub ahead of print]16(23):
    Antioxidant and Antiaging Activity of Houttuynia cordata Thunb. Ethyl Acetate Fraction in Caenorhabditis elegans.
    Hyeon-Ji Kim, Ji-Su Mun, Suk-Heung Oh, Jun-Hyung Kim.
       BACKGROUND/OBJECTIVES: In aerobic organisms, such as humans, oxygen radicals are inevitably produced. To counteract oxidation, the body generates antioxidant substances that suppress free radicals. However, levels of reactive oxygen species (ROS) increase due to aging and lifestyle factors, leading to exposure to various diseases. While synthetic antioxidants offer advantages like high stability, low cost, and availability, their safety remains controversial. This study aimed to investigate the antioxidant and antiaging activities of Houttuynia cordata (HC), which is rich in flavonoids and has excellent antioxidant properties, using Caenorhabditis elegans as a model.
    METHODS: Extraction and fractionation of HC were performed to evaluate antioxidant activities (DPPH, ABTS, superoxide radical scavenging activity) and antiaging effects (lifespan). The ethyl acetate fraction (EAF) with the highest activity was selected for further investigation.
    RESULTS: The EAF of HC exhibited high levels of polyphenols and flavonoids, presenting the highest DPPH, ABTS, and superoxide radical scavenging activities. This fraction increased the activity of antioxidant enzymes in nematodes in a concentration-dependent manner and provided resistance to oxidative stress, reducing ROS accumulation. Additionally, the fraction enhanced the lifespan of nematodes, improved resistance to heat stress, increased survival rates, and decreased the accumulation of aging pigments (lipofuscin). The expression of daf-2, daf-16, and sir-2.1, proteins directly involved in nematode aging, was confirmed. Liquid chromatography/tandem mass spectrometry identified quercitrin in the HC extract, which may contribute to its antioxidant and antiaging effects.
    CONCLUSIONS: The EAF of HC demonstrates significant potential for influencing antioxidant and antiaging, as evidenced by functional investigations using C. elegans.
    Keywords:  Caenorhabditis elegans; Houttuynia cordata; anti-aging; anti-oxidant
    DOI:  https://doi.org/10.3390/nu16234168
  28. Nature. 2024 Dec 18.
    Spatial transcriptomic clocks reveal cell proximity effects in brain ageing.
    Eric D Sun, Olivia Y Zhou, Max Hauptschein, Nimrod Rappoport, Lucy Xu, Paloma Navarro Negredo, Ling Liu, Thomas A Rando, James Zou, Anne Brunet.
      Old age is associated with a decline in cognitive function and an increase in neurodegenerative disease risk1. Brain ageing is complex and is accompanied by many cellular changes2. Furthermore, the influence that aged cells have on neighbouring cells and how this contributes to tissue decline is unknown. More generally, the tools to systematically address this question in ageing tissues have not yet been developed. Here we generate a spatially resolved single-cell transcriptomics brain atlas of 4.2 million cells from 20 distinct ages across the adult lifespan and across two rejuvenating interventions-exercise and partial reprogramming. We build spatial ageing clocks, machine learning models trained on this spatial transcriptomics atlas, to identify spatial and cell-type-specific transcriptomic fingerprints of ageing, rejuvenation and disease, including for rare cell types. Using spatial ageing clocks and deep learning, we find that T cells, which increasingly infiltrate the brain with age, have a marked pro-ageing proximity effect on neighbouring cells. Surprisingly, neural stem cells have a strong pro-rejuvenating proximity effect on neighbouring cells. We also identify potential mediators of the pro-ageing effect of T cells and the pro-rejuvenating effect of neural stem cells on their neighbours. These results suggest that rare cell types can have a potent influence on their neighbours and could be targeted to counter tissue ageing. Spatial ageing clocks represent a useful tool for studying cell-cell interactions in spatial contexts and should allow scalable assessment of the efficacy of interventions for ageing and disease.
    DOI:  https://doi.org/10.1038/s41586-024-08334-8
  29. Subcell Biochem. 2024 ;107 183-203
    Resveratrol and Its Analogues: Anti-ageing Effects and Underlying Mechanisms.
    Dan-Dan Zhou, Jin Cheng, Jiahui Li, Si-Xia Wu, Ruo-Gu Xiong, Si-Yu Huang, Peter Chi-Keung Cheung, Hua-Bin Li.
      Ageing is a natural process accompanied by functional and structural decline of diverse tissues and organs, which could cause susceptibility to various diseases and death. The anti-ageing interventions have aroused huge research interest with the rapid rise of ageing population in the world. Resveratrol, a polyphenolic stilbene, could be naturally isolated from various plants, such as grapes, blueberries, and peanuts. Many studies indicated that resveratrol possessed a broad spectrum of bioactivities, especially anti-ageing activity. A lot of attention has also been focused on resveratrol analogues because they have a similar structure to resveratrol, which may confer them a potent anti-ageing effect. The anti-ageing mechanisms of resveratrol and its analogues are complex and multifactorial, involving suppressing oxidative stress, ameliorating inflammation, activating SIRT1 pathway, reducing DNA damage, etc. In this chapter, the anti-ageing effects of resveratrol and its analogues are summarised with special attention paid to the underlying mechanisms. Further understanding of these small molecules could provide the necessary scientific basis for their development into anti-ageing agents.
    Keywords:  Ageing; Anti-ageing; Longevity; Piceatannol; Pterostilbene; Resveratrol
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_9
  30. Nutrients. 2024 Nov 30. pii: 4156. [Epub ahead of print]16(23):
    Broccoli Sprout Extract Suppresses Particulate-Matter-Induced Matrix-Metalloproteinase (MMP)-1 and Cyclooxygenase (COX)-2 Expression in Human Keratinocytes by Direct Targeting of p38 MAP Kinase.
    Jaehyeok Yun, Jong-Eun Kim.
       BACKGROUND/OBJECTIVES: Particulate matter (PM) is an environmental pollutant that negatively affects human health, particularly skin health. In this study, we investigated the inhibitory effects of broccoli sprout extract (BSE) on PM-induced skin aging and inflammation in human keratinocytes.
    METHODS: HaCaT keratinocytes were pretreated with BSE before exposure to PM. Cell viability was assessed using the MTT assay. The expression of skin aging and inflammation markers (MMP-1, COX-2, IL-6) was measured using Western blot, ELISA, and qRT-PCR. Reactive oxygen species levels were determined using the DCF-DA assay. Kinase assays and pull-down assays were conducted to investigate the interaction between BSE and p38α MAPK.
    RESULTS: Our findings demonstrate that BSE effectively suppressed the expression of MMP-1, COX-2, and IL-6-critical skin aging and inflammation markers-by inhibiting p38 MAPK activity. BSE binds directly to p38α without competing with ATP, thereby selectively inhibiting its activity and downstream signaling pathways, including MSK1/2, AP-1, and NF-κB.
    CONCLUSIONS: These results suggest that BSE is a potential functional ingredient in skincare products to mitigate PM-induced skin damage.
    Keywords:  broccoli sprout extract (BSE); p38; particulate matter (PM); skin
    DOI:  https://doi.org/10.3390/nu16234156
  31. Nature. 2024 Dec 18.
    Lithocholic acid binds TULP3 to activate sirtuins and AMPK to slow down ageing.
    Qi Qu, Yan Chen, Yu Wang, Weiche Wang, Shating Long, Heng-Ye Yang, Jianfeng Wu, Mengqi Li, Xiao Tian, Xiaoyan Wei, Yan-Hui Liu, Shengrong Xu, Jinye Xiong, Chunyan Yang, Zhenhua Wu, Xi Huang, Changchuan Xie, Yaying Wu, Zheni Xu, Cixiong Zhang, Baoding Zhang, Jin-Wei Feng, Junjie Chen, Yuanji Feng, Huapan Fang, Liyun Lin, Z K Xie, Beibei Sun, Huayu Tian, Yong Yu, Hai-Long Piao, Xiao-Song Xie, Xianming Deng, Chen-Song Zhang, Sheng-Cai Lin.
      Lithocholic acid (LCA) is accumulated in mammals during calorie restriction and it can activate AMP-activated protein kinase (AMPK) to slow down ageing1. However, the molecular details of how LCA activates AMPK and induces these biological effects are unclear. Here we show that LCA enhances the activity of sirtuins to deacetylate and subsequently inhibit vacuolar H+-ATPase (v-ATPase), which leads to AMPK activation through the lysosomal glucose-sensing pathway. Proteomics analyses of proteins that co-immunoprecipitated with sirtuin 1 (SIRT1) identified TUB-like protein 3 (TULP3), a sirtuin-interacting protein2, as a LCA receptor. In detail, LCA-bound TULP3 allosterically activates sirtuins, which then deacetylate the V1E1 subunit of v-ATPase on residues K52, K99 and K191. Muscle-specific expression of a V1E1 mutant (3KR), which mimics the deacetylated state, strongly activates AMPK and rejuvenates muscles in aged mice. In nematodes and flies, LCA depends on the TULP3 homologues tub-1 and ktub, respectively, to activate AMPK and extend lifespan and healthspan. Our study demonstrates that activation of the TULP3-sirtuin-v-ATPase-AMPK pathway by LCA reproduces the benefits of calorie restriction.
    DOI:  https://doi.org/10.1038/s41586-024-08348-2
  32. Subcell Biochem. 2024 ;107 245-268
    Role of Vitamin B in Healthy Ageing and Disease.
    Kathleen Mikkelsen, Maria Trapali, Vasso Apostolopoulos.
      B vitamin complex consist of vitamins B1, B2, B5, B6, B9, B12 and is pivotal for overall health, influencing vital functions such as, energy metabolism, DNA maintenance, and healthy immune system. Inadequate B vitamin levels are associated with various health issues, including neurocognitive problems, immune imbalances, and inflammation. In ageing individuals, deficiencies in B vitamins increase the risk of cardiovascular ailments, stroke, cognitive disorders, neurodegeneration, mental health issues, and methylation-related disorders. These result primarily due to changes in glycation, mitochondria, and oxidative stress. Thus, ensuring optimal vitamin B levels in the ageing population may be beneficial in preventing such age-related diseases. In this chapter we discuss the extensive role of B vitamins in the ageing process.
    Keywords:  Ageing; Cobalamin; Folate; Niacin; Pyridoxine; Riboflavin; Thiamine; Vitamin B
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_12
  33. Subcell Biochem. 2024 ;107 21-41
    Proteasome Activators and Ageing: Restoring Proteostasis Using Small Molecules.
    Arun Upadhyay, Vibhuti Joshi.
      Ageing is an inevitable phenomenon that remains under control of a plethora of signalling pathways and regulatory mechanisms. Slowing of cellular homeostasis and repair pathways, declining genomic and proteomic integrity, and deficient stress regulatory machinery may cause accumulating damage triggering initiation of pathways leading to ageing-associated changes. Multiple genetic studies in small laboratory organisms focused on the manipulation of proteasomal activities have shown promising results in delaying the age-related decline and improving the lifespan. In addition, a number of studies indicate a prominent role of small molecule-based proteasome activators showing positive results in ameliorating the stress conditions, protecting degenerating neurons, restoring cognitive functions, and extending life span of organisms. In this chapter, we provide a brief overview of the multi-enzyme proteasome complex, its structure, subunit composition and variety of cellular functions. We also highlight the strategies applied in the past to modulate the protein degradation efficiency of proteasome and their impact on rebalancing the proteostasis defects. Finally, we provide a descriptive account of proteasome activation mechanisms and small molecule-based strategies to improve the overall organismal health and delay the development of age-associated pathologies.
    Keywords:  Ageing; Lifespan; Proteasome; Small molecules; Ubiquitin-proteasome system
    DOI:  https://doi.org/10.1007/978-3-031-66768-8_2
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