bims-caglex 2025-08-03 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–08–03
eleven papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Pharmacological frontiers in senescence: Transforming senescence with drug repurposing.
Cellular senescence and senotherapeutics in cardiovascular diseases.
Pharmacological potential of calorie restriction mimetics in mitigating brain aging.
Oxygen-ozone adjunct therapy in aging and senescence-related disorders. State of art.
Topical Application of Bio-Pulsed Avian MSC-Derived Extracellular Vesicles Enhances Hair Regrowth and Skin Rejuvenation: Evidence from Clinical Evaluation and miRNA Profiling.
Integrating biological age, epigenetic clocks, and telomere length in precision nutrition strategies for chronic disease management: Potential frameworks and ongoing challenges.
Senotherapeutic approach to age-related endocrine diseases.
Sex as a major determinant of pro-longevity drug efficacy: a review of two decades of the NIA Interventions Testing Program.
High-frequency quantitative ultrasound in characterizing human skin aging: an exploration of the non-modeling and modeling approaches.
Advances in mesenchymal stem cell and exosome-based therapies for aging and age-related diseases.
Associations Between Antiprotozoal Treatments and Reduced Mortality Across Populations Suggest That Protozoal Colonization May Contribute Significantly to Human Mortality and Age-Related Morbidity.

Adv Pharmacol. 2025 ;pii: S1054-3589(25)00051-1. [Epub ahead of print]104 121-176

Pharmacological frontiers in senescence: Transforming senescence with drug repurposing.

Andleeb Shahzadi, Sibel Ozyazgan, Ufuk Çakatay.

  Repurposing conventional drugs as senotherapeutics offers a pragmatic and efficient approach to targeting cellular senescence, a key driver of aging-related diseases. Instead of relying solely on novel drug development, repurposing allows for the use of existing drugs with well-characterized pharmacokinetics, safety profiles, and clinical data, thereby accelerating their translation into senescence-targeted interventions. This chapter provides a comprehensive classification of senotherapeutics into senolytics, senomorphics, senoblockers, and senoreversers, detailing their mechanisms of action, molecular targets, and therapeutic applications. By categorizing these conventional agents based on their functional roles, this chapter presents a structured framework for understanding the pharmacological landscape of senotherapeutics. Additionally, this chapter discusses tissue-specific targeting, optimizing the dosing strategy to enhance the precision and safety of repurposed senotherapeutics. This chapter offers a systematic evaluation of drug repurposing, bridges the gap between preclinical and clinical applications, addressing both opportunities and challenges in repurposing the drugs. Eventually, this approach holds the potential to extend healthspan, mitigate age-related dysfunction, and provide more accessible and effective therapeutic options for disorders associated with cellular senescence.

Keywords:  Clinical trials; Drug repurposing; Optimizing dosing strategies; Pharmacological approaches

DOI:  https://doi.org/10.1016/bs.apha.2025.02.010
Adv Pharmacol. 2025 ;pii: S1054-3589(25)00037-7. [Epub ahead of print]104 313-349

Cellular senescence and senotherapeutics in cardiovascular diseases.

Arttatrana Pal.

  Cellular senescence (CS) is characterized by stable cell cycle arrest and is resistant to growth-promoting stimuli allied with aging. Cardiac senescent cells (SCs) are highly heterogeneous cells that can regulate the pathophysiology of cardiovascular diseases (CVDs). SCs accumulate in the cardiovascular system, leading to typical age-related cardiovascular conditions. Such conditions advance in cardiovascular pathologies, including heart failure, coronary artery disease, cardiac fibrosis, etc., by evocating the production of proinflammatory mediators and profibrotic senescence-associated secretory phenotype (SASP). SCs release different factors depending on the cell type that became senescent. Many factors are responsible for CS with the aging process. The primary senescence causes are oxidative stress, metabolic dysfunction, telomere shortening, and epigenetic deregulation. However, it isn't easy to understand the molecular mechanisms that lead to CS and the consequences of CS in developing new strategies and therapeutic approaches to treat CVDs. Among all, senotherapies are an emerging approach for intervening against CS mechanisms in CVDs to potentially prevent and treat CVDS. Senotherapies allow targeting the underlying causes of aging rather than treating disorders and could reduce polypharmacy. Essentially, senotherapeutics represent an emerging anti-SC treatment and comprise three therapeutic approaches such as molecules to selectively kill SCs that are defined senolytics, compounds able to reduce evocated SC SASP, acting hence as SASP suppressors, called senomorphics, and inhibition of increase of the number of SCs in the cardiovascular tissues. Senotherapies might delay or prevent the CVDs in the elderly. Therefore, senotherapeutics represent the potential clinical application in CVDs, stressing benefits and signifying potential solutions for applying them as soon as effective anti-CVD treatments.

Keywords:  Cardiac aging; Cardiovascular diseases; Cellular senescence; Senolytics; Senomorphics; Senotherapy

DOI:  https://doi.org/10.1016/bs.apha.2025.01.019
Adv Pharmacol. 2025 ;pii: S1054-3589(25)00044-4. [Epub ahead of print]104 177-197

Pharmacological potential of calorie restriction mimetics in mitigating brain aging.

Varsha Pai, Ishika Singh, Abhishek Kumar Singh.

  Quality of life is strongly influenced by brain aging, which is closely associated with neurodegeneration. With brain aging, various changes occur at the cellular, tissue, and organ levels, such as loss of proteostasis; dysregulation of nutrient sensing; abnormalities in the functions of mitochondria; and changes in neurophysiology. These changes also affect cognitive capabilities and result in mild to severe cognitive impairment. The three main mechanisms of brain aging, namely, senescence, inflammation, and oxidative stress, are being investigated in experimental models. Interventions such as caloric restriction, ketone diets, and intermittent fasting have shown the potential for slowing brain aging by modulating nutrition-sensing pathways, which improve metabolic health, decrease oxidative stress, and reduce inflammatory responses. However, noncompliance with these traditional interventions makes them inefficient. To overcome this drawback, caloric restriction mimetics (CRMs), which tend to produce greater effects than traditional methods without affecting dietary intake, are better therapeutic options. This chapter focuses on the transition of CRMs from preclinical to clinical trials in humans.

Keywords:  Brain aging; Caloric restriction mimetics; Clinical trials; Dietary interventions; Preclinical trials

DOI:  https://doi.org/10.1016/bs.apha.2025.02.003
Adv Pharmacol. 2025 ;pii: S1054-3589(25)00063-8. [Epub ahead of print]104 417-446

Oxygen-ozone adjunct therapy in aging and senescence-related disorders. State of art.

Salvatore Chirumbolo, Giovanni Ricevuti, Marianno Franzini, Francesco Vaiano, Antonio Carlo Galoforo, Tommaso Richelmi, Umberto Tirelli, Luigi Valdenassi.

  Ozone therapy presents as a promising yet controversial approach to anti-aging and health rejuvenation, due to an ongoing and crucially debated need for standardization about protocols, procedures, and dosages. While it offers potential benefits in improving skin health, boosting energy levels, and reducing inflammation, its use must be carefully considered only by specialized, highly trained experts and professionals, due to potential risks related to malpractice and shallow or clumsy fashion trends. The ability of ozone to address senescent mechanisms and aging-related processes makes this adjunct therapy a promising approach for aging-related impairments, such as neurodegenerative disorders and cardiovascular pathologies.

Keywords:  Aging; Chaos; Complexity; Fractality; Ozone; Senescence; Therapy

DOI:  https://doi.org/10.1016/bs.apha.2025.03.001
Curr Issues Mol Biol. 2025 Jul 11. pii: 539. [Epub ahead of print]47(7):

Topical Application of Bio-Pulsed Avian MSC-Derived Extracellular Vesicles Enhances Hair Regrowth and Skin Rejuvenation: Evidence from Clinical Evaluation and miRNA Profiling.

Ju-Sheng Shieh, Yu-Tang Chin, Tsu-Te Yeh, Jiong Jiong Guo, Fung-Wei Chang, Hui-Rong Cheng, Hung-Han Hsu, Wei-Lun Huang, Han-Hsiang Huang, Ya-Yu Hsieh, Chien-Ping Chiang, Shih-Ching Wang.

  Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have emerged as promising therapeutic agents in regenerative dermatology. This study evaluated the safety and efficacy of Bio-Pulsed avian mesenchymal stem cell-derived sEVs (AMSC-sEVs), topically applied for hair follicle stimulation and skin rejuvenation. Two prospective, single-arm clinical trials were conducted: one involving 30 participants using a hair ampoule over 60 days, and the other involving 30 participants applying a facial essence for 28 days. Objective measurements demonstrated significant improvements in the anagen/telogen hair ratio, reduced shedding, increased collagen density, and reduced wrinkle depth and pigmentation. Small RNA sequencing and qPCR profiling confirmed that Bio-Pulsed AMSC-sEVs were enriched with regenerative microRNAs, such as miR-21-5p and miR-199a-5p, associated with anti-inflammatory and anti-aging effects. No adverse events were reported. These findings suggest that Bio-Pulsed AMSC-sEVs may offer a safe, non-invasive, and cell-free approach to enhance skin and hair regeneration in human subjects.

Keywords:  Bio-Pulsed priming; avian mesenchymal stem cells; clinical trial; collagen biosynthesis; extracellular vesicles; hair follicle activation; microRNA profiling; non-invasive therapy; regenerative dermatology; skin rejuvenation

DOI:  https://doi.org/10.3390/cimb47070539
Nutr Res. 2025 Jun 29. pii: S0271-5317(25)00088-0. [Epub ahead of print]140 135-160

Integrating biological age, epigenetic clocks, and telomere length in precision nutrition strategies for chronic disease management: Potential frameworks and ongoing challenges.

Beatriz G Carvalho, Amanda A Ribeiro, Jhulia C N L da Mota, Lucas M Carvalho, Carolina F Nicoletti.

  Precision nutrition is emerging as a transformative strategy for optimizing health, particularly in the context of biological aging and chronic disease prevention. This review aims to examine how biological age markers-specifically telomere length and epigenetic clocks-can be integrated into precision nutrition frameworks to personalize interventions, enhance chronic disease management, and support healthy aging. Telomere length is a widely studied biomarker of aging and chronic disease risk, while epigenetic clocks, based on DNA methylation patterns, offer complementary insights into biological age, gene expression, and disease susceptibility. Nutritional interventions rich in antioxidants, omega-3 fatty acids, polyphenols, B vitamins, and anti-inflammatory compounds have shown potential to modulate these biomarkers, supporting cellular health and delaying aging processes. In addition, lifestyle factors such as physical activity, stress management, and adequate sleep play critical roles in maintaining telomere integrity and epigenetic stability. However, challenges remain in translating these biomarkers into clinical practice. Importantly, variability is not the only barrier; most of these biomarkers still lack clinical validation, and there is no consensus on standardized protocols or reference values that would support their routine application in healthcare. Current guidelines recommend combining telomere length and epigenetic age with other molecular markers, such as multi-omics data, within integrative biological age assessment approaches. Nevertheless, translating this approach into clinical practice will require overcoming significant limitations, including the validation of biomarkers, standardization of measurement techniques, cost-effectiveness, and the development of clear clinical guidelines. Continued research is essential to confirm their predictive value and practical utility in precision nutrition strategies aimed at promoting healthy aging and preventing chronic diseases.

Keywords:  Age-related biomarkers; Chronic disease; DNA methylation clocks; Personalized nutrition; Telomere integrity

DOI:  https://doi.org/10.1016/j.nutres.2025.06.010
Adv Pharmacol. 2025 ;pii: S1054-3589(25)00050-X. [Epub ahead of print]104 475-514

Senotherapeutic approach to age-related endocrine diseases.

Şeydanur Turgut, Gülnur Andican.

  Senescent cells progressively accumulate in the endocrine glands and their target tissue during the biological aging process. Senescence leads to hormonal imbalances contributing to various age-related endocrine diseases (AREDs). Cellular senescence, characterized by irreversible cell-cycle arrest, becomes more prevalent in advanced age, and the senescent cells release pro-inflammatory and pro-fibrotic factors, exacerbating endocrine dysregulation. Senescence-associated secretory phenotype (SASP) contributes to the pathogenesis of AREDs such as metabolic syndrome, sarcopenia, osteoporosis, and type 2 diabetes mellitus. Impaired metabolism of melatonin, cortisol, insulin, growth, and thyroid hormones are all intimately linked to age-related hormonal imbalance and dysregulated circadian rhythms. Pharmacokinetic and pharmacodynamic processes are also known to be impacted by circadian oscillations, which can also impact the toxicity and effectiveness of several therapeutic agents. Diagnosing and monitoring AREDs requires an assessment of individual circadian oscillations, inappropriate polypharmacy, and the senotherapeutic benefits of routine medications in the elderly. Hormone-oriented senotherapeutic strategies combined with anti-inflammatory SASP-related treatments may alleviate the detrimental effects of ARED symptoms. However, the complexity of senotherapy and the risk of possible adverse effects necessitate personalized treatment approaches.

Keywords:  Age-related endocrine diseases; Circadian rhythm; Hormones; Polypharmacy; Senescence; Senotherapeutics

DOI:  https://doi.org/10.1016/bs.apha.2025.02.009
J Gerontol A Biol Sci Med Sci. 2025 Jul 24. pii: glaf138. [Epub ahead of print]80(8):

Sex as a major determinant of pro-longevity drug efficacy: a review of two decades of the NIA Interventions Testing Program.

Nisi Jiang, Ziying Xu, Shangang Zhao, Jonathan Gelfond, Randy Strong, James F Nelson.

  Aging is the primary risk factor for frailty, sarcopenia, and functional decline, as well as cancer, cardiovascular and neurodegenerative diseases. Gaining insight into the biological mechanisms of aging could lead to interventions that broadly reduce age-related morbidity and mortality. To identify interventions that extend lifespan and delay aging, the National Institute on Aging launched the Interventions Testing Program (ITP) in 2004. This multi-site effort uses genetically heterogeneous UM-HET3 mice to evaluate the effects of candidate compounds. Over the past two decades, the ITP has tested 54 agents in more than 30, 000 mice. This is the first comprehensive review of the program's results, with particular emphasis on a striking pattern of sex-specific responses. By presenting the full scope of the findings, readers can better understand the overall impact of the program and easily access detailed information on specific drugs of interest. Notably, most compounds that extended lifespan were effective primarily or exclusively in male mice. Dosage and age of treatment onset influenced efficacy and were also sexually dimorphic. These sex differences suggest that mechanisms of aging are sexually dimorphic and highlight the importance of recognizing biological sex as a modifier of treatment efficacy. Investigating the basis for these differences should enable more targeted and effective geroprotective strategies for both sexes.

Keywords:  interventions; lifespan; longevity; sex differences

DOI:  https://doi.org/10.1093/gerona/glaf138
Quant Imaging Med Surg. 2025 Jul 01. 15(7): 6372-6385

High-frequency quantitative ultrasound in characterizing human skin aging: an exploration of the non-modeling and modeling approaches.

Yuzhen Li, Bingbing He, Xun Lang, Guang Shi, Ningtao Zhang, Zhenyu Guo, Yufeng Zhang.

   Background: High-frequency quantitative ultrasound (HQUS) technology, with its non-invasiveness, high-resolution, objectivity, and reproducibility, holds significant potential for characterizing skin aging through the analysis of the internal structure of tissues. This study aims to explore a framework for characterizing skin aging assessment through HQUS technology to facilitate the subsequent analysis of skin aging-related studies.
Methods: In this study, an exploration of non-modeling and modeling HQUS techniques in characterizing skin aging was conducted. In particular, we tested the conventional approach using the envelope amplitude, the non-modeling approach based on the small-window entropy and the modeling approach with the Nakagami parameters (m and Ω) at scanning depths of 1 and 1.5 mm, respectively, and discovered that such a characterization framework is well-suitable for quantifying skin aging. These parameters were calculated based on ultrasound backscattered signals at a high frequency of 42 MHz from the facial skin (from the epidermis to the dermis) of 70 female participants aged 24-57 years and then analyzed using the linear fitting and receiver operating characteristic (ROC) curves.
Results: The results show that there exists a linear correlation between all parameters and participant ages at scanning depths of 1 and 1.5 mm, respectively. Among them, the correlation coefficients for parameter m are r2=0.84 (P<0.0001) and r2=0.65 (P<0.0001), which are higher than those for the relative envelope amplitude, small-window entropy, and parameter Ω. Moreover, the parameter m also has the highest area under the curve among the ROC curves, regardless of the scanning depth.
Conclusions: This characterization framework, especially the modeling of the Nakagami parameter m, has great feasibility for the characterization of human skin aging. The proposed framework holds significant potential for assessing the efficacy of facial rejuvenation products, photofacials, and similar treatments.

Keywords:  Nakagami parameter; Skin aging; envelope amplitude; high-frequency ultrasound; small-window entropy

DOI:  https://doi.org/10.21037/qims-24-1753
Stem Cell Res Ther. 2025 Jul 26. 16(1): 401

Advances in mesenchymal stem cell and exosome-based therapies for aging and age-related diseases.

Hang Li, Lin Bai.

  Mesenchymal stem/stromal cells (MSCs) and their exosomes (MSC-Exos) have great potential for tissue repair and regenerative medicine, which can improve the symptoms and prognosis of aging-related diseases and potentially slow the aging process through multiple pathways. This comprehensive review summarizes the characterization of MSCs and MSC-Exos from various tissue sources and their applications in treating diseases associated with aging, such as premature ovarian failure (POF), Alzheimer's disease (AD), atherosclerosis (AS), and osteoporosis (OP). MSCs exert therapeutic effects through multiple mechanisms, including differentiation into various cell types, secretion of bioactive molecules, and immune response regulation. MSC-Exos, which contain a diverse array of proteins, miRNAs, and other biomolecules, can deliver MSC-derived bioinformatics to target cells and demonstrate comparable therapeutic benefits to MSCs. This review highlights the signaling pathways and molecular mechanisms underlying the therapeutic efficacy of MSCs and MSC-Exos in age-related diseases, and further discusses the importance of MSC and MSC-Exo tissue source selection for specific disease applications and the potential of combination therapies and preconditioning strategies to enhance their therapeutic outcomes. Despite promising preclinical and clinical results, challenges such as uneven distribution, in vivo environmental maladaptation, apoptosis, and immune responses need to be addressed before widespread clinical application. Future research requires multidisciplinary collaboration to further elucidate the mechanisms of action and develop optimized therapeutic strategies for the prevention and treatment of age-related pathologies using MSCs and MSC-Exos.

Keywords:  Aging-related diseases; Cell therapy; Exosomes; Mesenchymal stem/Stromal cells

DOI:  https://doi.org/10.1186/s13287-025-04318-1
medRxiv. 2025 Jul 03. pii: 2025.07.01.25330644. [Epub ahead of print]

Associations Between Antiprotozoal Treatments and Reduced Mortality Across Populations Suggest That Protozoal Colonization May Contribute Significantly to Human Mortality and Age-Related Morbidity.

Ariel Israel, Abraham Weizman, Sarah Israel, Shai Ashkenazi, Eytan Ruppin, Shlomo Vinker, Eli Magen, Eugene Merzon.

To identify medications with the potential to increase human lifespan, we conducted a systematic screening of electronic health records from a national health organization, comparing medications consumed over the preceding decade by individuals over 60 who outlived the average life expectancy with those consumed by matched individuals who died before reaching it. This screen identified two antiprotozoal agents, atovaquone-proguanil and mefloquine, as strongly associated with increased longevity (odds ratios for 10-year mortality: 0.43 and 0.32; FDR = 0.0002 and 0.0001, respectively). We validated these associations in the U.S.-based TriNetX federated network, confirming that these two antiprotozoals, along with nirmatrelvir-ritonavir-a medication used to prevent severe COVID-19 outcomes and possessing antiprotozoal properties-were associated with significantly reduced mortality and a lower incidence of major age-related conditions, including diabetes mellitus, cardiovascular and cerebrovascular diseases, renal insufficiency, dementia, pulmonary disease, liver disease, and malignancies. Across both populations, antiprotozoal exposure was also associated with increased risks of specific adverse outcomes, notably hearing loss, Sjögren's syndrome, and lichen planus. The consistent observation of both benefits and risks across independent populations supports the biological plausibility of these effects and argues against confounding by indication or underdiagnosis. Taken together, these findings suggest that elimination of protozoal parasites-notably Toxoplasma gondii - may significantly reduce human age-related morbidity and mortality while increasing the risk of specific auditory, ophthalmic, and dermatologic complications. These results offer promising new avenues to extend human lifespan and promote healthy aging through targeted antimicrobial interventions.

DOI: https://doi.org/10.1101/2025.07.01.25330644