bims-caglex 2025-07-27 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–07–27
nineteen papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

PAI-1 is a common driver of aging and diverse diseases.
Developing a novel aging assessment model to uncover heterogeneity in organ aging and screening of aging-related drugs.
Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.
Recombinant Type III Humanized Collagen Solution for Injection Improves Skin Photoaging in Chinese Population: A Case Series.
Demystifying common DNA methylation sites that promote the ability of CheekAge to associate with health and disease.
Restoration of SIRT3 Expression in Aged Mice Alleviates UUO-Induced Renal Fibrosis by Reducing GSK-3β Hyperacetylation.
Pharmacologic interventions targeting ovarian aging, cancer, and mitochondrial dysfunction: An updated evidence.
Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments.
Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.
Clinical Safety and Efficacy of Hyaluronic Acid-Niacinamide-Tranexamic Acid Injectable Hydrogel for Multifactorial Facial Skin Quality Enhancement with Dark Skin Lightening.
Reprogramming aging: genetically enhanced mesenchymal progenitor cells show systemic rejuvenation in primates.
Large language model-based biological age prediction in large-scale populations.
Circulating microRNAs and cross sectional and longitudinal measurements of physical functioning and frailty: an explorative study in older twins.
Comparative efficacy of topical interventions for facial photoaging: a network meta-analysis.
Genome-wide association and epidemiological evidence linking air pollution to aging mechanisms.
Adipose-derived stem cell exosomes: multifaceted therapeutic applications in regenerative medicine.
Engineered M2 Macrophage-Derived Exosomes: Mechanisms and Therapeutic Potential in Inflammation Regulation and Regenerative Medicine.
Macroalgae-Inspired Brominated Chalcones as Cosmetic Ingredients with the Potential to Target Skin Inflammaging.
Dissolvable microneedles based on active components of Chinese Herbal Medicine for enhanced treatment of skin diseases.

Biomed J. 2025 Jul 18. pii: S2319-4170(25)00066-6. [Epub ahead of print] 100892

PAI-1 is a common driver of aging and diverse diseases.

Alireza Khoddam, Toshio Miyata, Douglas Vaughan.

  Plasminogen activator inhibitor-1 (PAI-1) is a key driver of aging and contributes to diverse pathologies. This review examines PAI-1's multifaceted contributions to aging. At the cellular level, PAI-1 amplifies senescence, exhausts stem cell niches, and disrupts metabolism. These cellular alterations translate into physiological decline: PAI-1 drives cardiovascular aging by promoting vascular senescence and arterial stiffening, contributes to cognitive decline by impairing amyloid-beta clearance, fuels cancer progression through angiogenesis and immune suppression, and exacerbates muscle atrophy by hindering regeneration. A rare loss-of-function SERPINE1 mutation extends lifespan, illustrating how lifelong PAI-1 reduction can positively impact the human healthspan. Looking forward, targeting PAI-1 with inhibitors could mitigate senescence, restore stem cell function, improve metabolic profile, enhance physiological health, and promise a longer healthspan.

Keywords:  Aging; Cognitive Decline; Muscle Atrophy; PAI-1; Senescence

DOI:  https://doi.org/10.1016/j.bj.2025.100892
Genome Med. 2025 Jul 24. 17(1): 83

Developing a novel aging assessment model to uncover heterogeneity in organ aging and screening of aging-related drugs.

Yingqi Xu, Maohao Li, Congxue Hu, Yawen Luo, Xing Gao, Xinyu Li, Xia Li, Yunpeng Zhang.

   BACKGROUND: The decline in organ function due to aging significantly impacts the health and quality of life of the elderly. Assessing and delaying aging has become a major societal concern. Previous studies have largely focused on differences between young and old individuals, often overlooking the complexity and gradual nature of aging.
METHODS: In this study, we constructed a comprehensive multi-organ aging atlas in mice and systematically analyzed the aging trajectories of 16 organs to elucidate their functional specificity and identify organ-specific aging trend genes. Cross-organ association analysis was employed to identify global aging regulatory genes, leading to the development of a multi-organ aging assessment model, hereafter referred to as the 2A model. The model's validity was confirmed using single-cell RNA sequencing data from aging mouse lungs, cross-species gene expression profiles, and pharmacogenomic data. Furthermore, a random walk algorithm and a weighted integration approach combining gene set enrichment analysis were implemented to systematically screen potential drugs for mitigating multi-organ aging.
RESULTS: The 2A model effectively assessed aging states in both human and mouse tissues and demonstrated predictive capability for senescent cell clearance rates. Compared to the sc-ImmuAging and SCALE clocks, the 2A model exhibited superior predictive accuracy at the single-cell level. Organ-specific analyses identified the lungs and kidneys as particularly susceptible to aging, with immune dysfunction and programmed cell death emerging as key contributors. Notably, single-cell data confirmed that plasma cell accumulation and naive-like cell reduction showed linear changes during organ aging. Aging trend genes identified in each organ were significantly enriched in aging-related functional pathways, enabling precise assessment of the aging process and determination of organ-specific aging milestones. Additionally, drug screening identified Fostamatinib, Ranolazine, and Metformin as potential modulators of multi-organ aging, with mechanisms involving key pathways such as longevity regulation and circadian rhythm.
CONCLUSIONS: The 2A model represents a significant advancement in aging assessment by integrating multi-dimensional validation strategies, enhancing its accuracy and applicability. The identification of organ-specific aging pathways and candidate pharmacological interventions provides a theoretical foundation and translational framework for precision anti-aging therapies.

Keywords:  Aging assessment model; Drug screening; Organ aging; Single-cell sequencing

DOI:  https://doi.org/10.1186/s13073-025-01501-0
Pharmacol Rev. 2025 Jun 26. pii: S0031-6997(25)07485-X. [Epub ahead of print]77(5): 100077

Cell and tissue reprogramming: Unlocking a new era in medical drug discovery.

Chandan K Sen, Andrew J Friday, Sashwati Roy.

Recent advancements in cell and tissue biology have fundamentally changed our understanding of cellular behavior, revealing that both stem and nonstem cells exhibit remarkable plasticity and adaptability. This discovery has paved the way for revolutionary medical drug therapies that leverage cell and tissue reprogramming to repair or regenerate damaged tissues, offering new hope for conditions that were once considered irreversible. Tissue reprogramming involves the activation of specific molecular pathways to convert the function of residual tissue to compensate for the loss of tissue function to aging, trauma, or disease processes. By targeting these pathways, emerging drugs can promote regenerative processes, enabling the restoration of tissue function lost due to aging, injury, or disease. These therapies have shown promising results in preclinical studies addressing a wide range of diseases. Unlike traditional treatments, which focus primarily on managing symptoms, tissue reprogramming therapies offer a dynamic approach that can fundamentally alter cellular states, leading to functional recovery. This review explores the current state of cell and tissue reprogramming, highlighting its potential applications in regenerative medicine and the challenges that must be addressed for successful clinical translation. As our understanding of cellular plasticity continues to evolve, these innovative therapies stand at the forefront of a new era in medicine, with the potential to transform treatment paradigms and significantly improve patient outcomes across a wide range of conditions. SIGNIFICANCE STATEMENT: Breakthrough technologies have transformed our understanding of cell and tissue biology, uncovering that cells and tissues possess remarkable adaptability and fluidity in their roles. This revelation has opened up exciting possibilities in regenerative medicine, where emerging drug therapies aim to harness and reprogram cells to repair or regenerate damaged tissues. An emerging class of medical drugs will activate the body's natural regenerative abilities, offering the potential to restore tissue function lost due to aging, injury, or disease.

DOI: https://doi.org/10.1016/j.pharmr.2025.100077
J Cosmet Dermatol. 2025 Jul;24(7): e70276

Recombinant Type III Humanized Collagen Solution for Injection Improves Skin Photoaging in Chinese Population: A Case Series.

Lin Tao, Yu Yi.

   BACKGROUND: Photoaging leads to structural changes in the skin, such as reduced collagen production, contributing to wrinkles, reduced elasticity, and dyspigmentation. Collagen-based treatments have shown promise in skin rejuvenation, but the effectiveness of recombinant type III humanized collagen (RhCol-III) solution for injection in Asian populations has not been widely studied.
AIMS: To evaluate the efficacy of RhCol-III solution injections in improving skin quality for rejuvenation among Chinese cases.
METHODS: Eight Chinese participants with Fitzpatrick phototype III/IV, presenting with signs of skin photoaging, underwent once a month intradermal injections of 2 mg/mL RhCol-III solution over a 90-day period. Clinical assessments, including VISIA imaging, ultrasound, cutometer, and self-assessed Global Aesthetic Improvement Scale (GAIS) scores, were conducted at baseline, 30, 60, and 90 days postinjection. Key skin parameters such as elasticity, firmness, wrinkle severity, pigmentation, and pore size were evaluated to assess the effectiveness of the RhCol-III solution.
RESULTS: Participants demonstrated significant improvements in skin quality, although variable due to individual response. VISIA imaging indicated enhanced skin tone evenness and radiance. Participants who had visible wrinkle reduction and pore size decrease, on further assessment, were found to have increased dermal thickness and density, along with improved skin elasticity and firmness. Most participants reported high levels of satisfaction with the treatment outcomes, and no significant adverse events were observed.
CONCLUSIONS: RhCol-III solution injections appear to be a safe and effective treatment for skin rejuvenation, offering improvements in elasticity, firmness, skin tone, and radiance. This case series brings out the potential of RhCol-III solution in providing substantial anti-photoaging benefits in Chinese facial skin.

Keywords:  Chinese population; photoaging; recombinant type III humanized collagen solution; skin rejuvenation

DOI:  https://doi.org/10.1111/jocd.70276
Ageing Res Rev. 2025 Jul 19. pii: S1568-1637(25)00185-0. [Epub ahead of print]111 102839

Demystifying common DNA methylation sites that promote the ability of CheekAge to associate with health and disease.

Adiv A Johnson, Maxim N Shokhirev.

  We recently showed that the next-generation epigenetic aging clock CheekAge was significantly associated with 33 different health and disease signals across 25 publicly available MethylationEPIC datasets. We additionally uncovered DNA methylation sites that played a disproportionately important role in driving the ability of CheekAge to associate with each of these variables. We dubbed these "pro" CpGs because of their ability to promote a given association. Here, we identify 2639 common DNA methylation sites that were a "pro" CpG for at least two different health and disease signals. Using genes annotated to these common "pro" CpGs, we perform extensive enrichment analyses to unveil motifs of DNA repair, cell division, tumors, cancer, and inherited syndromes. We additionally show that a plethora of genes linked to these common "pro" CpGs have been reported to alter lifespan and/or healthspan in model organisms when manipulated. Some of these were highly germane to canonical signaling pathways, such as RPTOR (encoding for Regulatory-associated protein of mTOR) and FOXA2 (encoding for Hepatocyte nuclear factor 3-beta). We also honed in on the seven DNA methylation sites that represented the most common "pro" CpGs, which were cg00005888, cg02478836, cg18331022, cg01892528, cg27634071, cg09232037, and cg17841124. Not only do we summarize available literature for these sites and their annotated genes, but we show that they can be combined into a proof-of-concept epigenetic biomarker that associates with alcohol intake, diet quality, and sex. All together, we provide additional insights into DNA methylation sites that underlie CheekAge's ability to associate with meaningful signals.

Keywords:  Aging biology; Aging biomarkers; Biohorology; Epigenetic aging clocks; Longevity; Next-generation clock

DOI:  https://doi.org/10.1016/j.arr.2025.102839
Adv Sci (Weinh). 2025 Jul 23. e17248

Restoration of SIRT3 Expression in Aged Mice Alleviates UUO-Induced Renal Fibrosis by Reducing GSK-3β Hyperacetylation.

Jing Wang, Xiang Ren, Huan Lu, Zihao Guo, Xing Li, Yiqun Tian, Yisheng Yin, Zhenliang Qin, Kun Yun, Minglong Wu, Gang Chen, Xiaoyong Zeng.

  Aging increases the vulnerability of kidneys to injury and impairs their regenerative capacity. SIRT3 expression declines with aging and is associated with multiple age-related pathologies. The expression profile and functional role of SIRT3 in renal aging remain unclear. Here, SIRT3 expression in aging kidneys is assessed and analyzed for its promoter methylation patterns using methylation-specific PCR (MSP). It is found that aging exacerbates UUO-induced renal fibrosis, associated with downregulated SIRT3 expression. Mechanistically, age-related SIRT3 downregulation is mediated by hypermethylation of its promoter region. SIRT3 knockout exacerbated renal fibrosis in young mice subjected to UUO, whereas SIRT3 overexpression attenuated fibrosis in aged UUO mice. Integration of RNA-seq and immunoprecipitation-mass spectrometry (IP-MS) analyses revealed that SIRT3 deficiency leads to hyperacetylation of GSK3β at lysine 15 (K15). This K15 hyperacetylation inhibited GSK3β activity, consequently stabilizing its substrate β-catenin. Furthermore, self-assembled PEG-PCL-PEG micelles are designed and synthesized to encapsulate hydrophobic honokiol (HKL). These micelles significantly enhanced the aqueous solubility and oral bioavailability of free HKL, maintained stable blood concentrations, and ultimately improved its anti-fibrotic efficacy. These findings propose novel therapeutic strategies for managing renal fibrosis in the aging population and provide a foundation for developing new drugs and combination therapies.

Keywords:  SIRT3; aging; deacetylation; kidney fibrosis; micelles; obstructive nephropathy

DOI:  https://doi.org/10.1002/advs.202417248
Biochim Biophys Acta Mol Basis Dis. 2025 Jul 17. pii: S0925-4439(25)00335-7. [Epub ahead of print]1871(8): 167987

Pharmacologic interventions targeting ovarian aging, cancer, and mitochondrial dysfunction: An updated evidence.

Alejandro Teppa-Garrán, Efraín Pérez-Peña, Luis Sobrevia, Reinaldo Marín.

  Ovarian aging is a major determinant of female reproductive longevity, characterized by declining oocyte quality and reduced ovarian reserve. With more women delaying childbearing, age-related infertility has become an urgent biomedical concern. Mitochondrial dysfunction plays a central role in this process, leading to oxidative damage and metabolic disturbances that impair oocyte competence. These alterations are linked to poorer outcomes in assisted reproductive technology (ART), particularly for women over 35, who face significantly reduced success rates. This review examines the key mechanisms of ovarian aging, including oxidative stress, DNA damage, telomere shortening, and mitochondrial dysfunction, all contributing to diminished oocyte quality and quantity. Special focus is given to sirtuins, especially SIRT1 and SIRT3, as critical regulators of redox balance in oocytes and granulosa cells. The review also addresses the impact of age-related changes on chromosomal cohesion and ovarian fibrosis. Importantly, mitochondrial insufficiency is increasingly recognized as a factor in broader age-related diseases, such as metabolic disorders and cancer, suggesting shared molecular pathways between reproductive aging and systemic health. Recent advances highlight the potential of targeted nutrient supplementation to modulate redox homeostasis, enhance sirtuin activity, and preserve mitochondrial function-strategies that may benefit both ovarian health and overall aging. This intersection of reproductive biology and mitochondrial medicine is driving interest in pharmacologic interventions to improve oocyte quality and mitigate age-related comorbidities.

Keywords:  Coenzyme Q10; DNA repair; Diabetes; Fertility; Mitochondrial dysfunction; Nicotinamide adenine dinucleotide; Ovarian aging; Oxidative stress; Sirtuins; cancer

DOI:  https://doi.org/10.1016/j.bbadis.2025.167987
Clin Transl Med. 2025 Jul;15(7): e70417

Addressing osteoblast senescence: Molecular pathways and the frontier of anti-ageing treatments.

Zhengdong Zhang, Pan Liu, Yu Song, Liang Ma, Yan Xu, Jie Lei, Bide Tong, Dingchao Zhu, Huaizhen Liang, Hongchuan Wang, Xingyu Zhou, Zixuan Ou, Junyu Wei, Hanpeng Xu, Di Wu, Shuchang Peng, Yifan Du, Zhi Du, Bingjin Wang, Zhiwei Liao, Wencan Ke, Kangcheng Zhao, Xiqin Xia, Lei Tan, Xiaobo Feng, Gang Liu, Shuai Li, Kun Wang, Cao Yang.

   BACKGROUND: Osteoblast senescence is a central driverof age-related osteoporosis. Accumulating evidence shows that counteractingthis senescence can substantially mitigate bone loss. In this review, we summarize the hallmarks of osteoblast senescence, the signaling pathways involved, and therapeutic strategies that target osteoblast senescence tocombat age-related osteoporosis.
METHODS: Chronic diseases associated with ageingpose a significant threat to human health. Studies have shown that osteoporosisis closely linked to the ageing process of the body and the senescence ofosteoblasts within the bone microenvironment. Counteracting the senescence ofosteoblasts and maintaining the balance of differentiation, proliferation andfunction between osteoclasts and osteoblasts has been a key focus in the research of age-related osteoporosis and bone loss. The biological behaviour andfunctionality of the osteoblast lineage related to senescence are modulated bya variety of targets, including signalling pathways, proteins and genes associated with ageing. This review aims to discuss the senescence-related characteristics of the osteoblast lineage, dissect the interplay and mechanisms between it and ageing-associated signalling pathways, proteinsand genes, as well as current strategies for the prevention and treatment ofosteoblast senescence.
CONCLUSION: This review systematically examines the regulatory interactions among markers, therapeutic targets, and signalingpathways associated with osteoblast senescence, alongside current potential strategies for targeting this process. It provides more comprehensive information for future research into the complex mechanisms underlying age-related osteoporosis driven by osteoblast senescence.
KEY POINTS: Osteoblast senescence is a key driver of age-related osteoporosis, disrupting bone formation and homeostasis. Aging impacts osteoblasts through multiple pathways, including telomere shortening, genomic instability, SASP secretion, and others. Bone loss related to osteoblast senescence involves the activation and crosstalk of multiple signaling pathways. The options for combating and treating osteoblast senescence toachieve anti-osteoporosis are numerous, but still challenging.

Keywords:  SASP; ageing‐related signalling pathways; anti‐ageing strategies; bone microenvironment; osteoblast senescence

DOI:  https://doi.org/10.1002/ctm2.70417
Acta Pharm Sin B. 2025 Jul;15(7): 3372-3403

Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.

Yajun Wang, Xueni Zhang, Mengli Qing, Wen Dang, Xuemei Bai, Yingjie Wang, Di Zhou, Lingjuan Zhu, Degang Qing, Juan Zhang, Gang Chen, Ning Li.

  Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.

Keywords:  Cross-talk; Intestinal aging; Intestinal epithelial renewal; Intestinal permeability; Intestine-derived systemic inflammation; Mechanism; Stem cell; Therapeutic strategy

DOI:  https://doi.org/10.1016/j.apsb.2025.05.011
Gels. 2025 Jun 26. pii: 495. [Epub ahead of print]11(7):

Clinical Safety and Efficacy of Hyaluronic Acid-Niacinamide-Tranexamic Acid Injectable Hydrogel for Multifactorial Facial Skin Quality Enhancement with Dark Skin Lightening.

Sarah Hsin, Kelly Lourenço, Alexandre Porcello, Michèle Chemali, Cíntia Marques, Wassim Raffoul, Marco Cerrano, Lee Ann Applegate, Alexis E Laurent.

  Facial aging is a complex process manifesting as skin hyperpigmentation, textural irregularities, and a diminished elasticity, hydration, and evenness of tone. The escalating demand for minimally invasive aesthetic interventions has driven the development of advanced hydrogel-based injectable formulations. This clinical study assessed the safety and efficacy of Hydragel A1, an injectable hydrogel containing hyaluronic acid (HA), niacinamide, and tranexamic acid (TXA), designed to simultaneously address multiple facets of facial skin aging. A cohort of 49 female participants underwent a series of objective and subjective assessments, including the Global Aesthetic Improvement Scale (GAIS), instrumental measurements (Antera 3D, Chromameter, Cutometer, Dermascan, Corneometer), and standardized photographic documentation at baseline (Day 0) and 14, 28, and 70 days post-treatment. The results demonstrated statistically significant improvements in skin hydration, texture, elasticity, and pigmentation following Hydragel A1 administration. Notably, no serious adverse events or significant injection site reactions were observed, confirming the favorable safety profile of the investigated device. Collectively, these findings underscore the potential of a combined HA, niacinamide, and TXA injectable formulation to provide a comprehensive approach to facial skin rejuvenation, effectively targeting multiple aging-related mechanisms.

Keywords:  aesthetic medicine; clinical trial; dermal fillers; facial aging; hyaluronic acid; hyperpigmentation; injectable therapeutics; niacinamide; skin texture; tranexamic acid

DOI:  https://doi.org/10.3390/gels11070495
Life Med. 2025 Aug;4(4): lnaf022

Reprogramming aging: genetically enhanced mesenchymal progenitor cells show systemic rejuvenation in primates.

Hongkun Wang, Yuanyuan Du.

DOI: https://doi.org/10.1093/lifemedi/lnaf022
Nat Med. 2025 Jul 23.

Large language model-based biological age prediction in large-scale populations.

Yanjun Li, Qi Huang, Jin Jiang, Xusheng Du, Wenxin Xiang, Shiqi Zhang, Zean Pan, Liyuan Zhao, Yuyan Cui, Limei Ke, Bo Yin, Linfeng Liu, Guoqing Feng, Shouyi Yan, Liangcai Gao, Yang Liu, Yujuan Yuan, Yanying Guo, Yuqing Yang, Weizhi Ma, Yining Yang, Qian Di.

Accurate and convenient assessment of individual aging is crucial for identifying health risks and preventing aging-related diseases. Nonetheless, current aging proxies often face challenges such as methodological limitations, weak associations with adverse outcomes and limited generalizability. Here we propose a framework that leverages large language models (LLMs) to estimate individual overall and organ-specific aging using only health examination reports. We validated this approach across six population-based cohorts, encompassing over 10 million participants and demonstrated effectiveness and reliability. Our results showed that the LLM-predicted overall age achieved a concordance index (C-index) of 0.757 (95% CI 0.752-0.761) for all-cause mortality, significantly outperforming other aging proxies such as telomere length, frailty index, eight epigenetic ages and four machine-learning models predictions. The overall age gap was strongly associated with multiple aging-related phenotypes and health outcomes, showing a hazard ratio of 1.055 (95% CI 1.050-1.060) for all-cause mortality. For organ-specific aging, LLM-predicted ages and age gaps also demonstrated superior performance in predicting corresponding organ-specific diseases compared to machine-learning models. Additionally, we examined the dynamic aging assessment capability of LLMs and applied age gaps to identify proteomic biomarkers associated with accelerated aging and to develop risk prediction models of 270 diseases. Interpretability analyses were also conducted to explore the decision-making process of LLMs. In conclusion, our LLM-based aging assessment framework offers a precise, reliable and cost-effective approach for estimating overall and organ-specific aging. It has potential for personalized aging assessment and health management in large-scale general populations.

DOI: https://doi.org/10.1038/s41591-025-03856-8
Mech Ageing Dev. 2025 Jul 16. pii: S0047-6374(25)00075-2. [Epub ahead of print] 112099

Circulating microRNAs and cross sectional and longitudinal measurements of physical functioning and frailty: an explorative study in older twins.

Rossella La Grotta, Cecilie Agergaard Sørensen, Asmus Cosmos Skovgaard, Mikael Thinggaard, Serena Dato, Giuseppina Rose, Jonas Mengel-From, Mette Soerensen.

  During aging, physical functioning declines, and disability and frailty increase; phenotypes which are bidirectionally linked. MicroRNAs (miRNAs) are epigenetic regulators of various physiological processes and suggested aging biomarkers. Here we investigate the association between circulating plasma miRNAs and hand grip strength, chair stand, (Rockwood) frailty, and activity of daily living (ADL) in 86 monozygotic twins (73-88 years). In cross-sectional analysis, both individual and twin-pair level analyses were performed, the latter controlling genetic confounding. The majority (74-100%) of miRNAs identified in the individual-level analysis were validated by twin-pair-level analysis, with 14 miRNAs showing significance (p<0.05) in both. Longitudinal analysis (up to eight years of follow-up) yielded more significant results (75-93 miRNAs), indicating that miRNAs might be more accurate in predicting functional decline over time. Of these miRNAs, seven showed consistent directions of effects across phenotypes. For all analyses, most (65-79%) of the observed effect sizes were negative, reflecting reduced functionality with increased miRNA levels. Enrichment analyses revealed pathways of gene expression (incl. p53- and FOXO-mediated transcription), signal transduction, the immune system, metabolism of RNA, among others. Of specific miRNAs, miR-1274a demonstrated negative association in both cross-sectional and longitudinal investigations of ADL. These findings support miRNAs as biomarkers of age-related functional decline.

Keywords:  Physical functioning; activity of daily living; frailty; micro RNAs; monozygotic twins

DOI:  https://doi.org/10.1016/j.mad.2025.112099
Sci Rep. 2025 Jul 24. 15(1): 26889

Comparative efficacy of topical interventions for facial photoaging: a network meta-analysis.

Lulu Lin, Xueqing Chen, Chuanhui Liu, Qiting Wang, Weishan Lian, Xin Xu, Yawei Guo, Huiyuan Zhong, Jiangming Zhong, Nan Zhao, Weibin Cheng, Peng Shu, Zhongzhi Xu.

  Chronic ultraviolet (UV) exposure is the primary cause of skin photoaging, leading to wrinkles, pigmentation changes, and loss of dermal elasticity. This systematic review and network meta-analysis evaluated the efficacy and safety of topical compounds for treating skin photoaging. A comprehensive search identified 23 RCTs with 3905 participants, comparing anti-aging agents. Bayesian network meta-analysis showed isotretinoin, retinol, and tretinoin significantly improved fine wrinkles, with isotretinoin ranked highest. Tazarotene was most effective for coarse wrinkles, while glycolic acid reduced roughness. Tretinoin and retinol were superior for hyperpigmentation. Safety analysis indicated tretinoin had the most favorable profile, whereas tazarotene and glycolic acid had higher adverse event risks. Isotretinoin and tretinoin emerged as the most balanced treatments across efficacy and safety. These findings provide evidence-based guidance for clinical decision-making in anti-photoaging therapy and underscore the potential for these agents to be integrated into routine dermatologic practice, particularly for patients seeking effective and well-tolerated topical interventions. However, limitations included limited racial diversity, potential commercial bias, and variability in dermatological assessments. These findings provide evidence-based guidance for clinical decision-making in anti-photoaging therapy.

Keywords:  Efficacy; Network meta-analysis; Safety; Skin photoaging; Topical compounds

DOI:  https://doi.org/10.1038/s41598-025-12597-0
J Hazard Mater. 2025 Jul 16. pii: S0304-3894(25)02189-2. [Epub ahead of print]496 139273

Genome-wide association and epidemiological evidence linking air pollution to aging mechanisms.

Xiao-Yu Liu, Dong Peng, Xu-Rui Liu, Yuan-Hui Sheng, Jun-Nan Zhao, Rong-Bin Xu, Dan Zhang, Bo Chen.

  This study aimed to investigate the effects of air pollution on aging and aging-related diseases, focusing on potential causal relationships and molecular mechanisms. The first part involved a comprehensive analysis of global studies, examining the associations among PM2.5 exposure, telomere length, and sarcopenia incidence. The second part employed Mendelian randomization (MR) analysis to explore potential causal association between PM2.5 exposure and shorter telomere length. Additionally, network analysis was conducted to identify the molecular pathways potentially linking PM2.5 to telomere length. Furthermore, extensive phenotypic association studies on aging have been performed. The comprehensive analysis indicated that PM2.5 exposure was associated with shorter telomere length and a greater incidence of sarcopenia. MR analysis provided evidence for a potential causal relationship between PM2.5 exposure and shorter telomere length. The network analysis results suggested several possible pathways for the association between PM2.5 and telomere length. Further phenotypic association studies on aging revealed a link between telomere length and the development of certain tumors. This integrative study provides novel evidence supporting a putative causal pathway from air pollution exposure to accelerated biological aging and aging-related diseases. These findings underscore the need for policies that reduce air pollution exposure and for more effective public health interventions.

Keywords:  Aging; Air pollution; Causal effect; PM(2.5); Telomere length

DOI:  https://doi.org/10.1016/j.jhazmat.2025.139273
Int J Surg. 2025 Jul 22.

Adipose-derived stem cell exosomes: multifaceted therapeutic applications in regenerative medicine.

Cheng-Shyuan Rau, Pao-Jen Kuo, Ching-Hua Hsieh.

  Adipose-derived stem cell exosomes (ADSC-Exos) have emerged as promising cell-free therapeutic agents in regenerative medicine, offering many benefits of stem cell therapy without the risks of cell transplantation. These nanoscale vesicles (30-150 nm) contain bioactive cargo including proteins, microRNAs, and lipids that mediate tissue repair through multiple mechanisms: promoting angiogenesis, modulating inflammation, reducing fibrosis, and activating endogenous regenerative pathways. Recent preclinical studies demonstrate remarkable efficacy across diverse applications, from accelerating chronic wound healing and stimulating skin regeneration to repairing cartilage, bone, and nerve tissues. In cardiovascular applications, ADSC-Exos protect against ischemic damage and improve cardiac function post-infarction. Neurologically, they show potential in stroke recovery, spinal cord injury, and neurodegenerative diseases by crossing the blood-brain barrier and delivering neuroprotective signals. Their potent immunomodulatory properties make them candidates for treating inflammatory and autoimmune conditions. Early clinical trials report encouraging safety profiles and preliminary efficacy in conditions ranging from acne scarring to Alzheimer's disease. However, significant challenges remain in standardizing isolation methods, ensuring consistent potency, scaling production to clinically relevant quantities, and establishing optimal delivery strategies. This review synthesizes recent advances and limitations in ADSC-Exo research across various clinical applications, examines their underlying mechanisms of action, discusses current translational challenges, and highlights the potential of these versatile nanoparticles to transform regenerative medicine as off-the-shelf, cell-free therapeutics for multiple disease states.

Keywords:  adipose-derived stem cells; exosomes; immunomodulation; regenerative medicine; tissue repair

DOI:  https://doi.org/10.1097/JS9.0000000000002841
Acta Biomater. 2025 Jul 18. pii: S1742-7061(25)00537-9. [Epub ahead of print]

Engineered M2 Macrophage-Derived Exosomes: Mechanisms and Therapeutic Potential in Inflammation Regulation and Regenerative Medicine.

Xuan Guan, Chengyu Li, Xinyi Wang, Liqing Yang, Yao Lu, Zehong Guo.

  M2 macrophage-derived exosomes (M2-Exos) are nanoscale vesicles enriched with bioactive cargo inherited from their parent M2 macrophages. Although M2-Exos emerge as a promising therapeutic agent due to their dual capacity of immunomodulation and tissue repair, they face critical limitations in applications, including low targeting specificity, cargo-loading capacity, and stability. Therefore, strategies are needed to construct engineered M2-Exos for enhancing therapeutic efficacy. In this review, we will first provide an overview of M2-Exos, including the preparation processes, parent cell sources, characterization, and delivery system. Second, we will examine advanced engineering approaches applied to M2-Exos, focusing on the enhancement of M2-Exos in terms of targeting specificity, payload retention, and microenvironment-responsive release kinetics. Third, we will introduce current applications of the engineered M2-Exos in the inflammatory diseases and regenerative medicine. The roles and the underlying therapeutic mechanisms of engineered M2-Exos in controlling inflammation and tissue regeneration are also discussed. Finally, we will also highlight the challenges in translating M2-Exos from bench to bedside, alongside perspectives for overcoming these barriers. By bridging mechanistic insights with emerging bioengineering technologies, future breakthroughs will unlock the full potential of engineered M2-Exos across precision therapy and cell-free tissue engineering. STATEMENT OF SIGNIFICANCE: M2 macrophage derived exosomes (M2-Exos) provide cell-free alternatives in regenerative medicine and immune regulation by utilizing the ability of M2 macrophages to regulate immune responses and coordinate tissue repair, yet their clinical translation is hindered by inherent limitations. Addressing these challenges through bioengineering strategies is critical to amplify their therapeutic efficacy and broaden clinical applicability. Recent advances in surface modification, cargo encapsulation, and stimulus-responsive delivery systems have significantly improved M2-Exos' targeting specificity, payload capacity, and controllability, making them precision tools for inflammatory diseases and regenerative medicine. This review not only provides a comprehensive framework for engineering M2-Exos but also offers insights into their mechanisms in resolving inflammation and promoting tissue repair.

Keywords:  Biomaterials; Exosomes; Inflammation; M2 macrophage; Tissue engineering

DOI:  https://doi.org/10.1016/j.actbio.2025.07.039
Mar Drugs. 2025 Jul 02. pii: 278. [Epub ahead of print]23(7):

Macroalgae-Inspired Brominated Chalcones as Cosmetic Ingredients with the Potential to Target Skin Inflammaging.

Ana Jesus, Sara Gimondi, Sónia A Pinho, Helena Ferreira, Nuno M Neves, Andreia Palmeira, Emília Sousa, Isabel F Almeida, Maria T Cruz, Honorina Cidade.

  Skin aging is mainly caused by external factors like sunlight, which triggers oxidative stress and chronic inflammation. Natural halogenated flavonoids have demonstrated anti-inflammatory properties. Inspired by the macroalgae-derived bromophenol BDDE, we investigated the anti-inflammatory potential of structure-related chalcones (1-7). Chalcones 1 and 7 showed the least cytotoxicity in keratinocyte and macrophage cells. Chalcones 1, 2, 4, and 5 exhibited the most significant anti-inflammatory effects in murine macrophages after lipopolysaccharide stimulation, with chalcone 1 having the lowest IC50 value (≈0.58 μM). A SNAP assay confirmed that chalcones do not exert their effects through direct NO scavenging. Symmetrical bromine atoms and 3,4-dimethoxy groups on both aromatic rings improved the anti-inflammatory activity, indicating a relevant structure-activity relationship. Chalcones 1 and 2 were selected for study to clarify their mechanisms of action. At a concentration of 7.5 μM, chalcone 2 demonstrated a rapid and effective inhibitory action on the protein levels of inducible nitric oxide synthase (iNOS), while chalcone 1 exhibited a gradual inhibitory action. Moreover, chalcone 1 effectively activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway with around a 3.5-fold increase at the end of 24 h at 7.5 μM, highlighting its potential as a modulator of oxidative stress responses. These findings place chalcone 1 as a promising candidate for skincare products targeting inflammation and skin aging.

Keywords:  Nrf2; anti-inflammatory activity; brominated chalcones; iNOS; macroalgae; skin aging

DOI:  https://doi.org/10.3390/md23070278
J Biomater Sci Polym Ed. 2025 Jul 22. 1-25

Dissolvable microneedles based on active components of Chinese Herbal Medicine for enhanced treatment of skin diseases.

Kai Ye, Ziyan Chen, Lan He, Huayi Wu, Zeyu Chen, Jing Tan.

  According to World Health Organization (WHO) estimates, around 900 million people globally are affected by various skin diseases, which cause significant physical and psychological distress and place a heavy economic burden on healthcare systems. The primary challenges in treating skin diseases include the limited transdermal drug absorption due to the skin barrier, the side effects associated with medications, and the recurring nature of these conditions that lead to prolonged patient suffering. Microneedles (MNs) have emerged as a promising transdermal drug delivery technology, able to painlessly penetrate the stratum corneum and deliver medications directly to the affected area. Various types of MNs technology have been developed, including dissolvable MNs (DMNs), solid MNs, coated MNs, hollow MNs, and hydrogel-based MNs. DMNs, especially, offer non-invasive drug delivery with sustained release through their dissolvable nature. Combining active ingredients from Chinese Herbal Medicine (CHM), known for their natural anti-inflammatory and antibacterial properties with minimal side effects, with DMNs provides an effective approach for treating skin diseases. This review aims to provide a comprehensive overview of the application of CHM-based DMNs in treating psoriasis, acne, hypertrophic scars, keloids, melanoma, atopic dermatitis, and other skin conditions. Additionally, it will introduce the manufacturing methods for CHM-based DMNs, explore strategies for integrating CHM with MNs, and summarize the broad translational potential and challenges of this technology in the field of dermatology.

Keywords:  Chinese Herbal Medicine; Skin disease; active components; dissolvable microneedles; drug delivery

DOI:  https://doi.org/10.1080/09205063.2025.2535492