bims-caglex 2025-03-09 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–03–09
thirty-one papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

Phytoextracts as Natural Anti-Aging Agents: Mechanisms and Strategies for Skin Rejuvenation.
Rejuvenation of Senescent Cells, In Vitro and In Vivo, by Low-Frequency Ultrasound.
Gerobiotics: Exploring the Potential and Limitations of Repurposing Probiotics in Addressing Aging Hallmarks and Chronic Diseases.
Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus.
Metformin alleviates auditory cell senescence by mitophagy induction.
Citrulline regulates macrophage metabolism and inflammation to counter aging in mice.
SRS microscopy identifies inhibition of vitellogenesis as a mediator of lifespan extension by caloric restriction in C. elegans.
Assessment of the Capability of Mesenchymal Stem Cells and/or Pyrroloquinoline Quinone in Compensating the Age-Related Dysfunctions of AMP-Activated Protein Kinase Pathway in Wistar Rats.
Involvement of SIRT1-mediated aging in liver diseases.
Ginseng in delaying brain aging: Progress and Perspectives.
Anti-senescence therapies: a new concept to address cardiovascular disease.
SIRT3 suppresses vascular endothelial senescence via DHRS2 and contributes to the anti-vascular aging effect of Bazi Bushen capsule.
Caenorhabditis Intervention Testing Program: all-trans retinoic acid-related compounds tamibarotene and bakuchiol do not extend lifespan in Caenorhabditis nematodes.
Blockade of ZMIZ1-GATA4 Axis Regulation Restores Youthfulness to Aged Cartilage.
Two polysaccharides from Polygonum multiflorum Thunb. exert anti-aging by regulating P53/P21 pathway and amino acid metabolism.
Dasatinib and Quercetin Mitigate Age-Related Alveolar Bone Inflammaging and Neutrophil Infiltration.
A secretome screen in primary human lung fibroblasts identifies FGF9 as a novel regulator of cellular senescence.
Restoration of angiogenic capacity in senescent endothelial cells by a pharmacological reprogramming approach.
Nanotherapy targeting anti-aging skin cells: harnessing ursolic acid from Ocimum sanctum Linn for precision skin rejuvenation - a molecular perspective.
Nutraceutical Interventions for Mitigating Skin Ageing: Analysis of Mechanisms and Efficacy.
Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease.
Structural characterizations and antiaging activities of hydrolyzed low-molecular-weight polysaccharides from Polygoni Multiflori Radix Praeparata.
17β-estradiol delays cardiac aging through suppressing the methylation of Beclin1 in a murine model.
Minerals and Trace Elements: Key Protectors of Skin Health and Defenders Against Skin Disorders.
SPRY1 regulates macrophage M1 polarization in skin aging and melanoma prognosis.
Lifestyles and their relative contribution to biological aging across multiple-organ systems: Change analysis from the China Multi-Ethnic Cohort study.
The nuclear pore complex connects energy sensing to transcriptional plasticity in longevity.
Effects of the VIVIFRAIL Exercise Protocol on Circulatory and Intracellular Peripheral Mediators Bridging Mitochondrial Dynamics and Inflammation in Robust and Frail Older People.
Current advances and future prospects of cell reprogramming in progeroid syndromes.
A Functional Skincare Formulation Mixed With Retinyl Propionate, Hydroxypinacolone Retinoate, and Vitamin C on Antiaging and Whitening Han Women in Shanghai, China.
Response to Article "Regenerative Potential Nanomedicine of Adipocyte Stem Cell-Derived Exosomes in Senescent Skin Tissue" [Letter].

Curr Aging Sci. 2025 Mar 03.

Phytoextracts as Natural Anti-Aging Agents: Mechanisms and Strategies for Skin Rejuvenation.

Vishakha Devi, Geeta Deswal, Ajmer Singh Grewal, Anjali Sharma, Kumar Guarve.

   INTRODUCTION: Skin aging is a complex biological process driven by intrinsic factors, such as genetics and cellular metabolism, and extrinsic factors, including environmental stressors like UV radiation, pollution, and lifestyle choices. These factors result in visible signs of aging, such as wrinkles, reduced skin elasticity, and pigmentation.
OBJECTIVE: This review presents the recent findings on phytoextracts as natural anti-aging agents, highlighting their bioactive compounds, mechanisms of action, and applications in skin rejuvenation.
METHODS: A comprehensive literature search was conducted in databases including Scopus, PubMed, and Web of Science, focusing on articles published from 2000 to 2023. Search terms such as "phytoextracts and skin aging," "natural antioxidants and collagen synthesis," and "bioactive compounds and skin rejuvenation" were used. Inclusion criteria involved peer-reviewed studies on phytoextracts with experimental evidence of anti-aging effects, focusing on human and in-vitro models. Exclusion criteria included non-English articles, review papers without experimental data, and studies unrelated to skin aging. Recent research articles focusing on skin aging mechanisms and the efficacy of phytoextracts were identified. Particular attention was given to the antioxidant, anti-inflammatory, and collagen-boosting properties of phytoextracts.
RESULTS: This study provides novel insights into the mechanisms through which phytoextracts counteract oxidative stress, inflammation, and extracellular matrix degradation. Notable examples include the role of resveratrol in activating longevity genes, curcumin in reducing UVinduced damage, and ginseng in improving skin elasticity. These compounds were found to exhibit potent anti-aging mechanisms through their antioxidant activity and collagen-boosting effects. Advanced delivery technologies, such as nanocarriers, enhance the efficacy of these bioactives.
CONCLUSION: Phytoextracts demonstrate significant potential in combating skin aging by reducing oxidative stress and inflammation, and enhancing collagen production. While the results are promising, further clinical studies are required to validate their long-term efficacy and safety in skin aging management.

Keywords:  Antioxidants; Bioactive compounds; Collagen synthesis; Natural anti-aging; Phytoextracts.; Skin aging

DOI:  https://doi.org/10.2174/0118746098363055250218040726
Aging Cell. 2025 Mar 03. e70008

Rejuvenation of Senescent Cells, In Vitro and In Vivo, by Low-Frequency Ultrasound.

Sanjay K Kureel, Rosario Maroto, Maisha Aniqua, Simon Powell, Ekta Singh, Felix Margadant, Brandon Blair, Blake B Rasmussen, Michael P Sheetz.

  The presence of senescent cells causes age-related pathologies since their removal by genetic or pharmacological means, as well as possibly by exercise, improves outcomes in animal models. An alternative to depleting such cells would be to rejuvenate them to promote their return to a replicative state. Here we report that treatment of non-growing senescent cells with low-frequency ultrasound (LFU) rejuvenates the cells for growth. Notably, there are 15 characteristics of senescent cells that are reversed by LFU, including senescence-associated secretory phenotype (SASP) plus decreased cell and organelle motility. There is also inhibition of β-galactosidase, p21, and p16 expression, telomere length is increased, while nuclear 5mC, H3K9me3, γH2AX, nuclear p53, ROS, and mitoSox levels are all restored to normal levels. Mechanistically, LFU causes Ca2+ entry and increased actin dynamics that precede dramatic increases in autophagy and an inhibition of mTORC1 signaling plus movement of Sirtuin1 from the nucleus to the cytoplasm. Repeated LFU treatments enable the expansion of primary cells and stem cells beyond normal replicative limits without altering phenotype. The rejuvenation process is enhanced by co-treatment with cytochalasin D, rapamycin, or Rho kinase inhibition but is inhibited by blocking Sirtuin1 or Piezo1 activity. Optimized LFU treatment parameters increased mouse lifespan and healthspan. These results indicate that mechanically induced pressure waves alone can reverse senescence and aging effects at the cellular and organismal level, providing a non-pharmacological way to treat the effects of aging.

Keywords:  aging; autophagy; calcium signaling; low frequency ultrasound; rejuvenation; senescence

DOI:  https://doi.org/10.1111/acel.70008
Probiotics Antimicrob Proteins. 2025 Mar 03.

Gerobiotics: Exploring the Potential and Limitations of Repurposing Probiotics in Addressing Aging Hallmarks and Chronic Diseases.

A G M Sofi Uddin Mahamud, Ishtiak Ahammed Tanvir, Md Ehsanul Kabir, Ismam Samonty, Md Anamul Hasan Chowdhury, Md Ashikur Rahman.

  As unhealthy aging continues to rise globally, there is a pressing need for effective strategies to promote healthy aging, extend health span, and address aging-related complications. Gerobiotics, an emerging concept in geroscience, offers a novel approach to repurposing selective probiotics, postbiotics, and parabiotics to modulate key aging processes and enhance systemic health. This review explores recent advancements in gerobiotics research, focusing on their role in targeting aging hallmarks, regulating longevity-associated pathways, and reducing risks of multiple age-related chronic conditions. Despite their promise, significant challenges remain, including optimizing formulations, ensuring safety and efficacy across diverse populations, and achieving successful clinical translation. Addressing these gaps through rigorous research, well-designed clinical trials, and advanced biotechnologies can establish gerobiotics as a transformative intervention for healthy aging and chronic disease prevention.

Keywords:  Aging hallmarks; Chronic disease prevention; Gerobiotics; Gut microbiota modulation; Health span extension; Longevity pathways

DOI:  https://doi.org/10.1007/s12602-025-10501-w
Commun Biol. 2025 Feb 28. 8(1): 331

Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus.

Fabien Pifferi, Jérémy Terrien, Julia Marchal, Alexandre Dal-Pan, Fathia Djelti, Martine Perret, Jacques Epelbaum, Stéphane Blanc, Jean-Luc Picq, Marc Dhenain, Fabienne Aujard.

Resveratrol (RSV), a polyphenol with anti-aging properties affecting metabolism and energy balance, is considered as a mimetic candidate to calorie restriction (CR). However its potential effects on delaying the onset of age-related diseases and increasing longevity have not yet been demonstrated in non-obese models close to humans such as non-human primates. The longitudinal monitoring of cognitive and motor performances, occurrence of age-related pathologies, age-related brain atrophy and mortality was performed from adulthood to death in a cohort of male grey mouse lemurs (Microcebus murinus, N = 33), all receiving 105 kJ/day of food but with a subset of 18 animals receiving RSV (200 mg.kg-1 body weight.day-1). RSV supplementation improved cognitive and motor performance at middle age as compared to control (CTL) animals. Median-lifespan was greater in RSV-fed animals (7.9 years compared to 6.4 years for CTL) but long-term RSV supplementation did not significantly affect all-cause nor age-related mortality. Also, brain grey matter atrophy accelerated in the RSV group at old age as compared to the CTL group. Altogether, these results suggest that long-term RSV supplementation procures health benefits at middle-age in male mouse lemurs but has limited long-term effects on health and longevity and might even impair brain integrity at older ages.

DOI: https://doi.org/10.1038/s42003-024-07387-9
Neurosci Res. 2025 Feb 27. pii: S0168-0102(25)00049-5. [Epub ahead of print]

Metformin alleviates auditory cell senescence by mitophagy induction.

Sung Il Cho, Eu-Ri Jo, Hee Sun Jang.

  Age-related hearing loss is the most common type of hearing loss in older adults. However, its underlying cellular mechanism is still unclear. Impaired mitochondrial function is a hallmark of various age-related pathologies. To maintain mitochondrial function in senescent cells, mitophagy is a crucial process for dysfunctional mitochondria turnover. Metformin has been reported to induce mitophagy. This study aimed to investigate the effect of metformin on preventing senescence in auditory cells. Low-dose H2O2 represented senescence-associated secretory phenotype (SASP) and reduced mitophagy-related molecules in House Ear Institute-Organ of Corti 1 (HEI-OC1) cells and cochlear explants. Metformin significantly decreased the expression of SASP in H2O2-induced senescent cells. Metformin also decreased the expression of senescence-associated p53 and p21, and increased the expression of mitophagy-related PINK1, Parkin, and BNIP3 in H2O2-induced senescent cells and cochlear explants. The co-localization of mitophagy dye and lyso dye decreased in H2O2-induced senescent cells, but metformin pre-treatment significantly increased their colocalization. Metformin significantly decreased the percentage of β-galactosidase-stained senescent cells and increased the expression of OXPHOS complexes in H2O2-induced senescent cells and cochlear explants. Metformin also significantly increased mitochondrial function in senescent cells. These results indicate that metformin prevented premature senescence in auditory cells by counteracting reduced mitophagy. Therefore, maintaining mitochondrial function using metformin might be a potential strategy for the prevention of age-related hearing loss.

Keywords:  Metformin; Mitochondria; Mitophagy; Senescence

DOI:  https://doi.org/10.1016/j.neures.2025.02.008
Sci Adv. 2025 Mar 07. 11(10): eads4957

Citrulline regulates macrophage metabolism and inflammation to counter aging in mice.

Zhangdan Xie, Moubin Lin, Beizi Xing, Hongmiao Wang, Haosong Zhang, Zimu Cai, Xinyu Mei, Zheng-Jiang Zhu.

Metabolic dysregulation and altered metabolite concentrations are widely recognized as key characteristics of aging. Comprehensive exploration of endogenous metabolites that drive aging remains insufficient. Here, we conducted an untargeted metabolomics analysis of aging mice, revealing citrulline as a consistently down-regulated metabolite associated with aging. Systematic investigations demonstrated that citrulline exhibited antiaging effects by reducing cellular senescence, protecting against DNA damage, preventing cell cycle arrest, modulating macrophage metabolism, and mitigating inflammaging. Long-term citrulline supplementation in aged mice yielded beneficial effects and ameliorated age-associated phenotypes. We further elucidated that citrulline acts as an endogenous metabolite antagonist to inflammation, suppressing proinflammatory responses in macrophages. Mechanistically, citrulline served as a potential inhibitor of mammalian target of rapamycin (mTOR) activation in macrophage and regulated the mTOR-hypoxia-inducible factor 1α-glycolysis signaling pathway to counter inflammation and aging. These findings underscore the significance of citrulline deficiency as a driver of aging, highlighting citrulline supplementation as a promising therapeutic intervention to counteract aging-related changes.

DOI: https://doi.org/10.1126/sciadv.ads4957
bioRxiv. 2025 Feb 03. pii: 2025.01.31.636008. [Epub ahead of print]

SRS microscopy identifies inhibition of vitellogenesis as a mediator of lifespan extension by caloric restriction in C. elegans.

Bowen Yang, Bryce Manifold, Wuji Han, Catherin DeSousa, Wanyi Zhu, Aaron Streets, Denis V Titov.

The molecular mechanisms of aging are not fully understood. Here, we used label-free Stimulated Raman scattering (SRS) microscopy to investigate changes in proteins and lipids throughout the lifespan of C. elegans . We observed a dramatic buildup of proteins within the body cavity or pseudocoelom of aged adults that was blunted by interventions that extend lifespan: caloric restriction (CR) and the reduced insulin/insulin-like growth factor signaling (IIS) pathway. Using a combination of microscopy, proteomic analysis, and validation with mutant strains, we identified vitellogenins as the key molecular components of the protein buildup in the pseudocoelom. Vitellogenins shuttle nutrients from intestine to embryos and are homologous to human apolipoprotein B, the causal driver of cardiovascular disease. We then showed that CR and knockdown of vitellogenins both extend lifespan by >60%, but their combination has no additional effect on lifespan, suggesting that CR extends the lifespan of C. elegans in part by inhibiting vitellogenesis. The extensive dataset of more than 12,000 images stitched into over 350 whole-animal SRS images of C. elegans at different ages and subjected to different longevity intervention will be a valuable resource for researchers interested in aging.

DOI: https://doi.org/10.1101/2025.01.31.636008
Cell Biochem Biophys. 2025 Mar 06.

Assessment of the Capability of Mesenchymal Stem Cells and/or Pyrroloquinoline Quinone in Compensating the Age-Related Dysfunctions of AMP-Activated Protein Kinase Pathway in Wistar Rats.

Kamal M Al Nishilli, Emad M El Zayat, Sherein S Abdelgayed, Mohamed Hosney, Nourhan Hassan.

  Aging is characterized by a decline in physiological functions and an increased susceptibility to age-related diseases. This study investigates the therapeutic potential of mesenchymal stem cells (MSCs) and pyrroloquinoline quinone (PQQ), individually and in combination, to counteract aging-related physiological declines, with a specific focus on their modulation of the AMP-activated protein kinase (AMPK) pathway, a key regulator of cellular energy homeostasis and stress response. Aging was induced in thirty-seven female rats using D-galactose, simulating the metabolic imbalances and oxidative stress characteristic of aging. The experimental groups included controls, aged rats without treatment, and aged rats treated with MSCs, PQQ, or a combined MSC-PQQ regimen. MSC homing analyses and Behavioral assessments, oxidative stress assays, gene expression profiling, histopathological evaluations were conducted to provide a multidimensional view of treatment efficacy. MSC homing confirmed successful tissue localization and repair, underscoring the regenerative capacity of MSCs. Remarkably, the combined MSC-PQQ therapy (APQQST) markedly improved anxiety-related behaviors, evidenced by increased rearing and grooming activities (p < 0.01). Oxidative stress biomarkers supported these findings; treated groups exhibited significantly reduced malondialdehyde (MDA) levels and elevated antioxidant defenses, including glutathione (GSH) and glutathione peroxidase (GPX) (p < 0.01). Gene expression analysis highlighted the beneficial upregulation of key genes such as LKB1, PFKFB3, TSC2, and HMGR, crucial for cellular energy homeostasis and stress response, with the combination therapy showing the most pronounced effects. Furthermore, histopathological assessments underscored significant liver tissue recovery in treated groups, particularly with combined treatment (APQQST), with minimal vacuolar degeneration and restored hepatic architecture (p < 0.01). These findings highlight the synergistic effects of MSCs and PQQ in mitigating behavioral, molecular, and physiological aspects of aging, underscoring their potential as promising therapeutic agents for promoting healthy aging and offering a foundation for future translational research and clinical applications.

Keywords:  AMPK pathway; Aging; Mesenchymal stem cells; Oxidative stress; Pyrroloquinoline quinone

DOI:  https://doi.org/10.1007/s12013-025-01693-7
Front Cell Dev Biol. 2025 ;13 1548015

Involvement of SIRT1-mediated aging in liver diseases.

Yueming Zhang, Chang Gong, Lina Tao, Jinghui Zhai, Fengwei Huang, Sixi Zhang.

  Liver disease is a significant global health issue, responsible for millions of deaths annually. Aging, characterized by the gradual decline in cellular and physiological functions, impairs tissue regeneration, increases susceptibility to liver diseases, and leads to a decline in liver health. Silent information regulator 1 (SIRT1), a NAD⁺-dependent deacetylase, has emerged as a pivotal factor in modulating age-related changes in the liver. SIRT1 preserves liver function by regulating essential aging-related pathways, including telomere maintenance, epigenetic modifications, cellular senescence, intercellular communication, inflammation, and mitochondrial function. Notably, SIRT1 levels naturally decline with age, contributing to liver disease progression and increased vulnerability to injury. This review summarizes the regulatory role of SIRT1 in aging and its impact on liver diseases such as liver fibrosis, alcoholic associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), and metabolic dysfunction-associated steatohepatitis (MASH), hepatocellular carcinoma (HCC). We also discuss emerging therapeutic approaches, including SIRT1 activators, gene therapy, and nutritional interventions, which are evaluated for their potential to restore SIRT1 function and mitigate liver disease progression. Finally, we highlight future research directions to optimize SIRT1-targeted therapies for clinical applications in age-related liver conditions.

Keywords:  SIRT1; aging; cellular senescence; liver diseases; therapeutic approaches

DOI:  https://doi.org/10.3389/fcell.2025.1548015
Phytomedicine. 2025 Mar 01. pii: S0944-7113(25)00227-2. [Epub ahead of print]140 156587

Ginseng in delaying brain aging: Progress and Perspectives.

Jingwen Niu, Guoqi Zhu, Junjie Zhang.

   BACKGROUND: The Shennong Bencao Jing (Shennong's Classic of Materia Medica) records that Panax ginseng C. A. Mey (ginseng) 'lightens the body and prolongs life'. Many investigations have documented that ginseng exerts neuroprotective effects by mitigating the aging of the brain. However, a comprehensive review of the impacts of ginseng on brain aging remains lacking.
PURPOSE: This study aims to review the advances in ginseng research regarding its role in delaying brain aging, focusing on its bioactive constituents, underlying mechanisms and potential side effects. The findings provide scientific pieces of evidence to support the medical utilization of ginseng in the delaying senescence and the management of aging-related diseases.
METHODS: This review includes studies on ginseng and brain aging in humans, retrieved from English-language research articles published between 2017 and the present in the PubMed and Web of Science databases. The work focused on ginseng, brain aging, and aging-related diseases, utilizing keywords such as "Ginseng", "Brain aging", "central nervous system", "intracellular homeostasis", "peripheral system", etc. RESULTS: Ginseng comprises a varied spectrum of biologically bioactive constituents, such as ginsenosides, Maillard reaction products, ginseng polysaccharides, volatile oils, amino acids, proteins, etc. These components work to contribute to their significant medicinal value. Based on the traditional Chinese medicine (TCM) theory that "the heart and brain are interconnected, the liver and brain are mutually supportive, the brain and spleen are related, the brain and lung are linked, and the brain and kidney work in harmony," we summarize that ginseng may sustain neural homeostasis through both central and peripheral perspectives. Additionally, the potential toxic side effects of ginseng are minimal.
CONCLUSION: Ginseng and its bioactive constituents exhibit considerable promise in delaying brain aging and treating neurodegenerative diseases. Future research should prioritize exploring the direct targets of ginseng and its active ingredients, and work toward establishing precise drug-target-efficacy relationships. This approach will facilitate the translation of these findings into clinically viable therapeutic approaches.

Keywords:  Active components; Brain aging; Ginseng; Intracellular homeostasis; Neurodegenerative diseases

DOI:  https://doi.org/10.1016/j.phymed.2025.156587
Cardiovasc Res. 2025 Feb 28. pii: cvaf030. [Epub ahead of print]

Anti-senescence therapies: a new concept to address cardiovascular disease.

Stevan D Stojanović, Thomas Thum, Johann Bauersachs.

Accumulation of senescent cells is an increasingly recognized factor in the development and progression of cardiovascular disease. Senescent cells of different types display a pro-inflammatory and matrix remodeling molecular program, known as the 'senescence associated secretory phenotype' (SASP), which has roots in (epi)genetic changes. Multiple therapeutic options (senolytics, anti-SASP senomorphics and epigenetic reprogramming) that delete or ameliorate cellular senescence have recently emerged. Some drugs routinely used in the clinics also have anti-senescence effects. However, multiple challenges hinder the application of novel anti-senescence therapeutics in the clinical setting. Understanding the biology of cellular senescence, advantages and pitfalls of anti-senescence treatments, as well as patients that can profit from these interventions is necessary to introduce this novel therapeutic modality into the clinics. We provide a guide through the molecular machinery of senescent cells, systematize anti-senescence treatments and propose a pathway towards senescence-adapted clinical trial design to aid future efforts.

DOI: https://doi.org/10.1093/cvr/cvaf030
Phytomedicine. 2025 Feb 25. pii: S0944-7113(25)00211-9. [Epub ahead of print]140 156571

SIRT3 suppresses vascular endothelial senescence via DHRS2 and contributes to the anti-vascular aging effect of Bazi Bushen capsule.

Yuan Zhao, Chunmei Zhang, Chen Zhang, Xuehui Zheng, Yan Qi, Binghui Kong, Yunlong Hou, Yun Ti, Peili Bu.

   AIMS: Vascular and endothelial aging are significant causes of chronic diseases among the elderly. This study investigated the specific mechanism by which sirtuin 3 (SIRT3) regulates vascular endothelial senescence and the beneficial role of Bazi Bushen capsule (BZBS) in preventing vascular aging.
METHODS: Human umbilical vein endothelial cells and mouse aortic endothelial cells were cultured with D-galactose (D-gal) to induce aging and evaluate the beneficial effects of the SIRT3-dehydrogenase/reductase member 2 (DHRS2) axis on the inhibition of vascular endothelial aging. d-Gal was injected intraperitoneally into wild-type and Sirt3 knockout mice, while BZBS was administered orally. Histochemical staining, immunohistochemistry, and western blotting assays were used to explore the beneficial effects of BZBS against aging-associated vascular remodelling. Endothelial cell function assays were used to evaluate the role of BZBS in suppressing endothelial aging in vitro.
RESULTS: SIRT3 deacetylated DHRS2 and modulated the translation of DHRS2. The SIRT3-DHRS2 axis played an important role in preserving mitochondrial homeostasis and reducing reactive oxygen species generation through suppressing endothelial nitric oxide synthase (eNOS) translocating to mitochondria and eNOS-Thr495 phosphorylation mediated by protein kinase C δ (PKCδ). BZBS mitigated vascular remodelling and relieved endothelial oxidative stress via the SIRT3-DHRS2 axis.
CONCLUSION: SIRT3 activates DHRS2-PKCδ to stop aging in endothelial cells by inhibiting uncoupled eNOS translocating to mitochondria. BZBS rescued vascular aging and endothelial dysfunction via the SIRT3-DHRS2 axis. Revealing a protective mechanism by which SIRT3 inhibits endothelial senescence, this study provides evidence for BZBS in delaying vascular aging.

Keywords:  Bazi Bushen capsule; DHRS2; Mitochondria; Oxidative stress; SIRT3; Vascular aging

DOI:  https://doi.org/10.1016/j.phymed.2025.156571
MicroPubl Biol. 2025 ;2025

Caenorhabditis Intervention Testing Program: all-trans retinoic acid-related compounds tamibarotene and bakuchiol do not extend lifespan in Caenorhabditis nematodes.

Stephen A Banse, Anna L Coleman-Hulbert, Christine A Sedore, Erik Johnson, Gordon J Lithgow, Monica Driscoll, Patrick C Phillips.

The Caenorhabditis Intervention Testing Program recently characterized the longevity-promoting effects of the vitamin A derivative all-trans retinoic acid (atRA). Here, we test two atRA-related compounds, tamibarotene and bakuchiol, for longevity effects in three strains of Caenorhabditis species. Both tamibarotene, a potent RAR agonist, and bakuchiol, a meroterpene derived from Psoralea corylifolia , showed no significant increase in lifespan across a dosage range of six concentrations. Additionally, bakuchiol was broadly toxic at higher doses. These findings highlight the specificity of atRA's longevity effects and suggest that compounds related to atRA may not universally promote lifespan extension.

DOI: https://doi.org/10.17912/micropub.biology.001517
Adv Sci (Weinh). 2025 Mar 05. e2404311

Blockade of ZMIZ1-GATA4 Axis Regulation Restores Youthfulness to Aged Cartilage.

Jiho Nam, Hyunmin Woo, Jihye Yang, Seok Jung Kim, Kwang Pyo Lee, Ji Hoon Yu, Tae Joo Park, Seong-Il Eyun, Siyoung Yang.

  Susceptibility to cartilage degeneration increases in an age-dependent manner and older cartilage exhibits increased catabolic factor expression leading to osteoarthritis (OA). While inhibition of cellular senescence can prevent age-related diseases, the understanding of the regulators governing cartilage senescence and the potential for senolytic intervention remains limited. Here, in vitro and in vivo results are reported, demonstrating for the first time that the transcriptional regulator, ZMIZ1, is upregulated in aged and OA cartilage, and that it acts through GATA4 to accelerate chondrocyte senescence and trigger cartilage deterioration. Furthermore, it is shown that K-7174 interferes with the ZMIZ1-GATA4 interaction and effectively hampers cartilage senescence and OA. It is proposed that inhibition of the ZMIZ1-GATA4 axis could be a valuable strategy for eliminating senescent chondrocytes and impeding OA development and that the relevant inhibitor, K-7174, could potentially be developed as a senolytic drug for managing cartilage senescence and age-related degeneration.

Keywords:  ZMIZ1‐GATA4 axis; cartilage restoration; osteoarthritis; senescence

DOI:  https://doi.org/10.1002/advs.202404311
Int J Biol Macromol. 2025 Feb 27. pii: S0141-8130(25)02124-5. [Epub ahead of print] 141573

Two polysaccharides from Polygonum multiflorum Thunb. exert anti-aging by regulating P53/P21 pathway and amino acid metabolism.

Jing Fan, Yaolei Li, Shuang Yang, Jianbo Yang, Hongyu Jin, Ying Wang, Feng Wei, Shuangcheng Ma.

  Polygonum multiflorum Thunb (PM) is known for its potential to extend lifespan. Although the polysaccharides, the primary constituents of PM, remain largely unexplored in terms of their anti-aging effects and underlying mechanisms, this study investigates them in detail. The anti-aging effects of two purified polysaccharides from PM were evaluated: neutral polysaccharide (RPMP-N, weight average molecular weight 245.30 kDa) and acidic polysaccharide (RPMP-A, weight average molecular weight 28.45 kDa), using a D-Galactose-induced (D-Gal) aging mouse model. In the experimental group, RPMP-N and RPMP-A were administered at doses of 50 (low) and 150 mg/kg/day (high). The activity of antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX), which are essential for scavenging free radicals and form a key part of the body's antioxidant defense system, was measured in aging mice. The results showed significant improvements following treatment with RPMP-N and RPMP-A. Additionally, both polysaccharides demonstrated the ability to repair and protect against liver and brain injuries. The expression of P16, P21, and P53 proteins, which regulate cellular senescence through distinct mechanisms, was significantly reduced in liver and brain tissues after treatment. Notably, untargeted metabolomics revealed that RPMP-N and RPMP-A exerted significant anti-aging effects in the D-Gal aging mouse model, primarily influencing metabolism pathways related to lysine, sphingolipids, cysteine, and methionine. In conclusion, these findings provide important insights into the anti-aging mechanisms of PM polysaccharides, supporting their potential for clinical applications, drug development, and regulatory science.

Keywords:  Anti-aging; Mechanisms; Metabolomics; Polygonum multiflorum Thunb; Polysaccharides

DOI:  https://doi.org/10.1016/j.ijbiomac.2025.141573
Oral Dis. 2025 Mar 06.

Dasatinib and Quercetin Mitigate Age-Related Alveolar Bone Inflammaging and Neutrophil Infiltration.

Jinru Tang, Jingya Li, Zeyu Hou, Rong He, Bingzhi Li, Jiajing Gong, Yuhang Xie, Wanrong Meng, Yunkun Liu, Takehito Ouchi, Longjiang Li, Bo Li.

   OBJECTIVE: Age-related alveolar bone resorption poses a major dental health challenge, yet its mechanisms and treatments are poorly understood. This study investigates the impact of dasatinib and quercetin (D + Q) treatment on senescent cells (SnCs), senescence-associated secretory phenotype (SASP), and neutrophil infiltration in aged alveolar bone, aiming to develop new strategies for combating age-related bone resorption.
METHODS: C57BL/6 mice (2 and 18 months) were used to examine alveolar bone resorption, inflammaging, and neutrophil infiltration. Aged mice received D + Q treatment to assess therapeutic effects. Key measurements included cementoenamel junction to the alveolar bone crest (CEJ-ABC) distance, periodontal ligament (PDL) thickness, osteometabolism markers, SnCs accumulation, SASP expression, and neutrophil infiltration.
RESULTS: Aged alveolar bone showed increased CEJ-ABC distance, atrophied periodontal ligament, and unbalanced osteometabolism, along with elevated SnCs, SASP, and neutrophils compared to young controls. D + Q treatment improved these conditions by reducing CEJ-ABC distance, enhancing periodontal ligament health, and boosting bone metabolism. It also lowered the expression of SnCs, SASP, and neutrophil markers.
CONCLUSION: D + Q treatment effectively mitigates alveolar bone aging by clearing SnCs, lowering SASP levels, and reducing neutrophil aggregation, presenting a novel approach for age-related bone resorption.

Keywords:  aging; inflammation; neutrophils; senescence‐associated secretory phenotype (SASP); senescent cells (SnCs); senolytics

DOI:  https://doi.org/10.1111/odi.15291
SLAS Discov. 2025 Feb 28. pii: S2472-5552(25)00016-4. [Epub ahead of print] 100223

A secretome screen in primary human lung fibroblasts identifies FGF9 as a novel regulator of cellular senescence.

Jenna Bradley, Patrick O'Shea, Catherine Wrench, Johann Mattsson, Roxane Paulin, Catherine Overed-Sayer, Laura Rosenberg, Henric Olsson, Davide Gianni.

  Senescent cells contribute to the pathogenesis of idiopathic pulmonary fibrosis (IPF), a disease with significant unmet need and therefore, there is an interest in discovering new drug targets that regulate this process. We design and perform a phenotypic screen with a secreted protein library in primary human lung fibroblasts to identify modulators of cell senescence. We identify FGF9 as a suppressor of several senescence phenotypes reducing stimulated p21 expression, enlarged morphology, DNA damage and SASP secretion, which is consistent with both DNA-damage and ROS induced senescence. We also show that FGF9 reduces fibroblast activation in both healthy and IPF fibroblasts shown by a reduction in pro-fibrotic markers such as α-smooth muscle actin and COL1A1 mRNA. Our findings identify FGF9 as a suppressor of both senescence and fibrotic features in lung fibroblasts and therefore could be targeted as a new therapeutic strategy for respiratory diseases such as IPF.

Keywords:  FGF9; fibroblasts; idiopathic pulmonary fibrosis; phenotypic screen; senescence

DOI:  https://doi.org/10.1016/j.slasd.2025.100223
PLoS One. 2025 ;20(2): e0319381

Restoration of angiogenic capacity in senescent endothelial cells by a pharmacological reprogramming approach.

Katrin Kalies, Kai Knöpp, Susanne Koch, Claudia Pilowski, Leonie Wurmbrand, Daniel Sedding.

Senescent endothelial cells (EC) are key players in the pathophysiology of cardiovascular diseases and are characterized by a reduced angiogenic and regenerative potential. Therefore, targeting these cells has been suggested as an effective therapeutic strategy to reduce vascular disease burden and potentially improve health and lifespan of humans. Here, we aimed to establish a pharmacological, partial reprogramming strategy to improve replicative senescent endothelial cell function in the context of angiogenesis. We demonstrate that our treatment improves tube formation and sprouting capacity but also increases proliferation and migration capacity in vitro. Further, inflammation and DNA damage were reduced in the replicative senescent cells. These processes were initiated by a short and timely-restricted overexpression of the Yamanaka-factors induced by our pharmacological strategy. The advantage of these compounds is that they are FDA approved in their respective concentrations which could pave the way for use in a clinical setting.

DOI: https://doi.org/10.1371/journal.pone.0319381
Nat Prod Res. 2025 Mar 06. 1-17

Nanotherapy targeting anti-aging skin cells: harnessing ursolic acid from Ocimum sanctum Linn for precision skin rejuvenation - a molecular perspective.

Shyamanta Bhattacharjee, Vaibhav Rastogi, Sumit Durgapal, Anurag Verma, Bhavana Singh, Amrish Chandra.

  The necessity of this work lies in the innovative application of nanotherapy to target anti-ageing skin cells, utilising ursolic acid from Ocimum sanctum Linn for precise and effective skin rejuvenation at a molecular level. Ursolic acid (UA), a pentacyclic triterpenoid compound, found in abundance in the plant O. sanctum Linn, has long been recognised for its potential anti-inflammatory, antioxidant, and anti-ageing properties. Despite its promising benefits, the direct application of UA in skincare has been limited, primarily due to its low aqueous solubility and poor skin penetration. This study explores a groundbreaking molecular approach, employing nanotechnology to enhance the delivery of UA, targeting skin cells for effective anti-ageing treatment. Through a comprehensive investigation, UA was encapsulated into biocompatible nanocarriers, ensuring increased stability, improved dermal penetration, and sustained release of the compound at the targeted site. By harnessing the specificity and efficiency of nanodelivery systems, the study achieved significant improvement in the absorption of UA in the deeper layers of the skin. This targeted intervention at the cellular and molecular level paved the way for maximising the potential of UA as an anti-ageing agent. In conclusion, the nanotherapeutic delivery of UA from O. sanctum Linn offers a paradigm shift in skincare, bringing forth a promising molecular strategy to combat skin ageing. With further advancements, this approach has the potential to revolutionise anti-ageing treatments, integrating traditional botanical wisdom with cutting-edge nanotechnology.

Keywords:  Ocimum sanctum linn; Ursolic acid; dermal fibroblasts; molecular approach; nanotherapy; skin aging

DOI:  https://doi.org/10.1080/14786419.2025.2474157
Curr Pharm Des. 2025 Mar 03.

Nutraceutical Interventions for Mitigating Skin Ageing: Analysis of Mechanisms and Efficacy.

Mohammad Ibrahim, Harpreet Singh, Mohd Fahim, Shabina Khan, Jalaluddin Khan, Jagdish Kumar Arun, Arun Kumar Mishra, Tarun Virmani, Ashwani Sharma, Girish Kumar, Dalapathi Gugulothu, Shivani Chopra, Hitesh Chopra.

  Skin ageing is influenced by intrinsic factors such as genetics and hormones, as well as extrinsic factors like environmental exposure, ultraviolet (UV) radiation, and diet. These factors lead to biochemical, biological, and structural changes in the skin. Plant-derived compounds with antioxidant and anti-inflammatory properties have emerged as potential anti-ageing agents. This comprehensive review, spanning data from 1997 to 2024, explores the role of nutraceuticals in skin anti-ageing. The research data were drawn from Google, PubMed, PubMed Central, Scopus, and various journal databases, including ScienceDirect, Springer, and Taylor & Francis. This review specifically examines plant-derived polyphenols, carotenoids, and other bioactive compounds, analysing their mechanisms through signalling pathways and cellular processes, using data from in vitro, in vivo, and clinical studies. Polyphenols like quercetin, curcumin, and epigallocatechin gallate (EGCG) have antioxidant and anti-inflammatory properties, helping to reduce oxidative stress, inflammation, UV-induced collagen degradation, and inflammatory cytokines. Notably, curcumin enhances collagen production and decreases the number of senescent cells. Carotenoids such as β-carotene, lutein, zeaxanthin, and lycopene protect against UV damage, and lycopene-rich tomato paste was specifically noted for its ability to reduce erythema and DNA damage. Additionally, compounds like resveratrol, fisetin, and wogonin exert protective effects against oxidative stress and inflammation, with resveratrol improving collagen synthesis and reducing the appearance of wrinkles. These plant-derived compounds can effectively combat skin ageing through various mechanisms, including the inhibition of oxidative stress, inflammation, and extracellular matrix degradation. They present a natural and sustainable approach to skincare in accord with the growing trend of conscious consumption. Future research should focus on understanding the long-term effects and determining the optimal dosage for clinical applications, highlighting the potential of integrating plant-based nutraceuticals into skincare regimens.

Keywords:  Skin ageing; minerals; nutraceuticals; skin anti-ageing.; vitamins

DOI:  https://doi.org/10.2174/0113816128336661250218080928
Prog Neurobiol. 2025 Feb 26. pii: S0301-0082(25)00034-6. [Epub ahead of print]247 102743

Partial reprogramming by cyclical overexpression of Yamanaka factors improves pathological phenotypes of tauopathy mouse model of human Alzheimer's disease.

Alejandro Antón-Fernández, Álvaro Ruiz de Alegría, Ana Mariscal-Casero, Marta Roldán-Lázaro, Rocío Peinado-Cauchola, Jesús Ávila, Félix Hernández.

  Partial reprogramming induced by the controlled and cyclical overexpression of Yamanaka factors in the nervous system has so far succeeded in reversing some aging-associated phenotypes, such as improving memory function. These promising results suggest that partial reprogramming could be a potential strategy to prevent or mitigate aging-related pathologies like tauopathies, including Alzheimer's disease. Here, we explore the potential of this strategy in addressing tauopathy development in the P301S mouse model. To achieve this, a new transgenic animal was created that can inducibly overexpress Yamanaka factors upon doxycycline administration and carries the Tau-P301S mutation, which leads to tauopathy development. The results of this study show a significant improvement in key pathological features of tauopathies in the hippocampus, including reversed tauopathy, alleviated reactive astrogliosis, age-related reduction of the H3K9me3 epigenetic marker, along with improved spatial memory, which has been described as deteriorated in this model. These findings reinforce the potential of partial reprogramming as a therapeutic strategy to combat brain pathologies associated with aging.

Keywords:  Alzheimer; GFAP; H3K9me3; Tau; Tau-P301S; Transgenic mice; Yamanaka factors; in vivo partial reprogramming

DOI:  https://doi.org/10.1016/j.pneurobio.2025.102743
Carbohydr Polym. 2025 May 15. pii: S0144-8617(25)00162-6. [Epub ahead of print]356 123381

Structural characterizations and antiaging activities of hydrolyzed low-molecular-weight polysaccharides from Polygoni Multiflori Radix Praeparata.

Wei Xu, Xue-Jian Li, Yu-Sen Zhong, Jia-Qi He, Wei Xie, You-Kun Kang, Hua-Zhong Ying, Chen-Huan Yu.

  Natural polysaccharides as the primary active components derived from herbal medicine often face challenges due to their large molecular weights, varying chemical structures and poor bioavailability, which significantly restrict their bioactive mechanism investigation and clinical applications. To improve the bioavailability and clarify the antiaging mechanism of polysaccharides from Polygoni Multiflori Radix Praeparata, the high-molecular-weight polysaccharides (PRP) were hydrolyzed into two low-molecular-weight fractions (PRP1 and PRP2) by hydrogen peroxide-ascorbic acid method. The results of structural characterization showed that they were glucans with the molecular weights of 13.43 kDa and 5.97 kDa, respectively. Compared with PRP and PRP1, PRP2 exhibited the most potent antiaging activity in D-galactose-treated T lymphocytes, attributed to its shorter chain length and lower molecular weight. Furthermore, oral administration with PRP2 not only decreased the levels of senescence-associated secretory phenotype (SASP)-related inflammatory cytokines, elevated the counts of T cells, NK cells, and macrophages in the blood, but also reduced the expressions of p16 and p21 proteins in spleen tissues of naturally aged C57BL/6J mice and two fast-aging (ERCC2+/- and TERT-/-) mice. Mechanistically, PRP2 competitively bound with Keap1 and subsequently activated Nrf2/HO-1 pathway. Therefore, PRP2 could be explored as a potential candidate for treatment of age-related diseases and overall aging.

Keywords:  Antiaging activity; Hydrolytic degradation; Low-molecular-weight polysaccharide; Nrf2/HO-1 pathway; Peripheral immune landscape; Senescence-associated secretory phenotype

DOI:  https://doi.org/10.1016/j.carbpol.2025.123381
Steroids. 2025 Mar 01. pii: S0039-128X(25)00028-5. [Epub ahead of print]216 109587

17β-estradiol delays cardiac aging through suppressing the methylation of Beclin1 in a murine model.

Lili Ye, Ruiyan Wang, Jun Zhao, Jingrong Chen, Feng Wang.

   INTRODUCTION: Cardiac endogenous senescence will gradually change and aggravate with age. Recent research showed that 17β-estradiol (17β-E2), an estrogen with numerous biological activities including the prevention of vascular senescence. However, how 17β-E2 against cardiac aging is still unknown. This work addressed the underlying mechanism with regard to Beclin1 and autophagy activity to better understand the anti-senescent effect of 17β-E2 on a well-established animal model of cardiac aging.
MATERIAL AND METHODS: In this study, an aging model in female mice was established using d-galactose and ovariectomy. Cardiac function was evaluated by echocardiography, RNA-seq was performed to analyze the gene expression profiles of myocardial tissues from 17β-E2 treated mice. Additionally,The levels of Beclin1, LC3, P62, and ATG5 in myocardial tissues were assessed using qPCR and Western blotting. Methylation levels of the Beclin1 promoter region in myocardial tissues were determined by MSP and BSP.
RESULTS: The findings demonstrated that cardiac aging mice treated with 17β-E2 had improved heart function. 17β-E2 restored EF(increase 1.25-fold) and FS(increase 1.2-fold) to near-normal levels. By RNA-sequencing and Gene Set Enrichment Analysis (GSEA) analysis, the autophagy signaling pathway was further enriched in the myocardial tissue of cardiac aging mice treated with 17β-E2, and we also discovered that 17β-E2 suppress the methylation of Beclin1 promoter region, which mediate the activation of autophagy signal.
CONCLUSIONS: Overall, our data showed that 17β-E2's anti-senescent effect on cardiac aging mice was mediated by the crucial suppression of methylation in the Beclin1 promoter area and subsequent activation of the autophagy signal, which may present a possible therapeutic approach to prevent cardiac aging.

Keywords:  17β-E2; Autophagy; Beclin1; Cardiac aging; Methylation

DOI:  https://doi.org/10.1016/j.steroids.2025.109587
Curr Med Chem. 2025 Mar 05.

Minerals and Trace Elements: Key Protectors of Skin Health and Defenders Against Skin Disorders.

Geir Bjørklund, Mariia Shanaida, Tetiana Gontova, Emma Gheorghe, Laura Kassym, Assiya Kussainova, Volodymyr Voloshyn, Yuliya Semenova, Roman Lysiuk, Olena Voloshyn, Volodymyr Shanaida, Tony Hangan.

  Skin is the human body's largest organ, protecting it from various environmental threats. At the same time, it is the most accessible organ of the body, which ensures the reception of stimuli and contact with the environment. Such common signs of skin aging, such as wrinkles, fine lines, and discoloration, result from both extrinsic and intrinsic factors that act for a long time. If the skin does not look well enough, it is worth investigating whether minerals or trace elements are deficient. The positive role of some minerals (calcium, potassium, sodium, sulfur, and magnesium) and trace elements (iron, zinc, selenium, copper, manganese, and silicon) was found in maintaining skin health. There are also a variety of skin conditions, such as inflammatory disorders (eczema, psoriasis), acne, lichen planus, vitiligo, alopecia areata, or even skin cancer, which require specific approaches for their prevention and treatment considering the saturation of the body and the skin with mineral elements. They could be supplied internally (through adequate nutrition or food additives) or externally (by application of cosmetics). Some aspects of the danger of the toxic trace elements used in cosmetics are also described in this review.

Keywords:  Skin health; antioxidants; dermatology; minerals; nutritional deficiencies.; trace elements

DOI:  https://doi.org/10.2174/0109298673348175250214054101
Transl Oncol. 2025 Feb 28. pii: S1936-5233(25)00062-2. [Epub ahead of print]54 102331

SPRY1 regulates macrophage M1 polarization in skin aging and melanoma prognosis.

Rongxin Zhao, Xun Zhang, Yingnan Geng, Dan Lu, Yuqing Wang, Han Xie, Xiaofei Zhang, Shunming Xu, Yanyun Cao.

   INTRODUCTION: Skin aging is a complex, multifactorial process involving cellular damage, inflammation, and increased susceptibility to diseases. Despite its importance, the role of SPRY1 in skin aging remains poorly understood. This study aims to investigate the function of SPRY1 in skin aging, particularly its impact on macrophage M1 polarization, and explore its potential as a therapeutic target for mitigating skin aging and melanoma.
METHODS: Bioinformatics analyses were performed using datasets from the GTEx and GEO databases, alongside in vitro cellular experiments. These included Weighted Gene Co-expression Network Analysis (WGCNA), single-cell sequencing, and various cellular assays in RAW264.7 murine monocyte/macrophage leukemia cells and NIH/3T3 mouse skin fibroblasts. The assays comprised gene transfection, Cell Counting Kit-8 (CCK-8) assays, quantitative real-time PCR (qRT-PCR), and measurements of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity.
RESULTS: SPRY1 was identified as a key gene within modules linked to skin aging. Single-cell sequencing revealed its enrichment in macrophages and keratinocytes. Knockdown of SPRY1 in RAW264.7 cells resulted in a shift from M1 to M2 macrophage polarization, reduced oxidative stress, and decreased expression of inflammatory markers. In NIH/3T3 cells, SPRY1 knockdown reduced cell viability and lowered the expression of inflammatory genes. Additionally, SPRY1 expression was downregulated in melanoma, and its reduced levels were associated with poorer survival outcomes.
CONCLUSIONS: SPRY1 accelerates skin aging by promoting macrophage M1 polarization and may serve as a promising therapeutic target. Future research should focus on in vivo validation and further exploration of its regulatory networks to develop novel treatments.

Keywords:  Bioinformatics analysis; Macrophage polarization; Melanoma; SPRY1; Skin aging

DOI:  https://doi.org/10.1016/j.tranon.2025.102331
Elife. 2025 Mar 07. pii: RP99924. [Epub ahead of print]13

Lifestyles and their relative contribution to biological aging across multiple-organ systems: Change analysis from the China Multi-Ethnic Cohort study.

Yuan Zhang, Dan Tang, Ning Zhang, Yi Xiang, Yifan Hu, Wen Qian, Yangji Baima, Xianbin Ding, Ziyun Wang, Jianzhong Yin, Xiong Xiao, Xing Zhao.

   Background: Biological aging exhibits heterogeneity across multi-organ systems. However, it remains unclear how is lifestyle associated with overall and organ-specific aging and which factors contribute most in Southwest China.
Methods: This study involved 8396 participants who completed two surveys from the China Multi-Ethnic Cohort (CMEC) study. The healthy lifestyle index (HLI) was developed using five lifestyle factors: smoking, alcohol, diet, exercise, and sleep. The comprehensive and organ-specific biological ages (BAs) were calculated using the Klemera-Doubal method based on longitudinal clinical laboratory measurements, and validation were conducted to select BA reflecting related diseases. Fixed effects model was used to examine the associations between HLI or its components and the acceleration of validated BAs. We further evaluated the relative contribution of lifestyle components to comprehension and organ systems BAs using quantile G-computation.
Results: About two-thirds of participants changed HLI scores between surveys. After validation, three organ-specific BAs (the cardiopulmonary, metabolic, and liver BAs) were identified as reflective of specific diseases and included in further analyses with the comprehensive BA. The health alterations in HLI showed a protective association with the acceleration of all BAs, with a mean shift of -0.19 (95% CI -0.34, -0.03) in the comprehensive BA acceleration. Diet and smoking were the major contributors to overall negative associations of five lifestyle factors, with the comprehensive BA and metabolic BA accounting for 24% and 55% respectively.
Conclusions: Healthy lifestyle changes were inversely related to comprehensive and organ-specific biological aging in Southwest China, with diet and smoking contributing most to comprehensive and metabolic BA separately. Our findings highlight the potential of lifestyle interventions to decelerate aging and identify intervention targets to limit organ-specific aging in less-developed regions.
Funding: This work was primarily supported by the National Natural Science Foundation of China (Grant No. 82273740) and Sichuan Science and Technology Program (Natural Science Foundation of Sichuan Province, Grant No. 2024NSFSC0552). The CMEC study was funded by the National Key Research and Development Program of China (Grant No. 2017YFC0907305, 2017YFC0907300). The sponsors had no role in the design, analysis, interpretation, or writing of this article.

Keywords:  biological aging; epidemiology; global health; healthy lifestyle; human; organ-specific aging

DOI:  https://doi.org/10.7554/eLife.99924
bioRxiv. 2025 Feb 17. pii: 2025.02.17.638704. [Epub ahead of print]

The nuclear pore complex connects energy sensing to transcriptional plasticity in longevity.

Yifei Zhou, Fasih M Ahsan, Alexander A Soukas.

As the only gateway governing nucleocytoplasmic transport, the nuclear pore complex (NPC) maintains fundamental cellular processes and deteriorates with age. However, the study of age-related roles of single NPC components remains challenging owing to the complexity of NPC composition. Here we demonstrate that the master energy sensor, AMPK, post-translationally regulates the abundance of the nucleoporin NPP-16/NUP50 in response to nutrient availability and energetic stress. In turn, NPP-16/NUP50 promotes transcriptomic activation of lipid catabolism to extend the lifespan of Caenorhabditis elegans independently of its role in nuclear transport. Rather, the intrinsically disordered region (IDR) of NPP-16/NUP50, through direct interaction with the transcriptional machinery, transactivates the promoters of catabolic genes. Remarkably, elevated NPP-16/NUP50 levels are sufficient to promote longevity and metabolic stress defenses. AMPK-NUP50 signaling is conserved to human, indicating that bridging energy sensing to metabolic adaptation is an ancient role of this signaling axis.

DOI: https://doi.org/10.1101/2025.02.17.638704
Aging Cell. 2025 Mar 04. e70029

Effects of the VIVIFRAIL Exercise Protocol on Circulatory and Intracellular Peripheral Mediators Bridging Mitochondrial Dynamics and Inflammation in Robust and Frail Older People.

Fiona Limanaqi, Evelyn Ferri, Pasquale Ogno, Franca Rosa Guerini, Gabriela Alexandra Mihali, Tiziano Lucchi, Mario Clerici, Chiara Fenoglio, Laura D'Andrea, Elena Marcello, Mara Biasin, Beatrice Arosio.

  Physical exercise has been associated with healthier aging trajectories, potentially preventing or mitigating age-related declines. This occurs through a complex, yet poorly characterized network of multi-organ interactions involving mitochondrial, inflammatory, and cell death/survival pathways. Here, we comprehensively evaluated the 12-week VIVIFRAIL multicomponent exercise protocol in physically frail (n = 16, mean age 81.4 ± 5.6) and robust (n = 50, mean-age 73.6 ± 4.7) old individuals. Before (T0) and after (T1) the protocol, functional outcomes were assessed alongside a detailed exploratory analysis of mitochondrial, inflammatory, apoptotic, and neuro-muscular mediators concerning their plasmatic/serum concentrations, and/or mRNA expression from peripheral blood mononuclear cells (PBMCs). Besides significant functional improvements across both groups, our findings highlighted unique and overlapping modulations of key biological pathways. Both groups showed refined mitochondrial integrity/turnover (upregulated mt-ND1, downregulated TFAM, and ULK1), anti-inflammatory responses (upregulated IL10, and TGF-B, and downregulated IL6/IL10 mRNA ratio), as well as reduced cellular damage/apoptosis (reduced plasmatic ccf-nDNA, downregulated BAX, and upregulated BCL-2/BAX ratio). Plasmatic ccf-mtDNA was significantly reduced in robust subjects, while plasmatic IL6 and IL6/IL10 ratio were reduced in frail subjects uniquely. Spearman correlations between physical improvements and biological pathway variations also suggested different adaptation mechanisms influenced not only by chronological age but also by frailty status. In conclusion, this study confirms the benefits of physical activity in the older population and provides novel insights into specific biological mediators of the mitochondria-inflammation axis as key players in such effects. Moreover, our findings establish PBMCs as a valuable tool for monitoring the biological trajectories of aging and health-promoting lifestyle interventions.

Keywords:  apoptosis; ccf‐mtDNA; cytokines; exercise; inflammaging; mitochondria; mitophagy; peripheral blood cells

DOI:  https://doi.org/10.1111/acel.70029
Front Cell Dev Biol. 2025 ;13 1546423

Current advances and future prospects of cell reprogramming in progeroid syndromes.

Lucas Moledo-Nodar, Víctor Celemín-Capaldi, Alejandro P Ugalde, José M P Freije.

  Cell reprogramming consists in the reverse process to cell differentiation, making cells lose their identity and age-related characteristics and granting an increased potential for proliferation and redifferentiation on different lineages. This process holds immense potential for the treatment of several pathologies, including progeroid syndromes, diseases that recapitulate the symptoms seen in physiological aging in an accelerated manner. Among the recent advances on the use of cell reprogramming in the context of progeroid syndromes, the interventions based on partial reprogramming, consisting on the dedifferentiation of cells only up to a point in which they lose age related characteristics but keep their identity, stand out. This partial reprogramming can be achieved both using the forced expression of transcription factors or cocktails of small molecules that regulate different biological processes. While all these advances are promising, the use of cell reprogramming in the treatment of progeroid syndromes still faces several challenges, such as the development of methods that allow for an efficient delivery of cell reprogramming factors in vivo and fine tuning of the dose used. Furthermore, these approaches should be accompanied by treatments targeting the original cause of the disease or they could be proven futile in the long term.

Keywords:  IPSC; aging; cell reprogramming; progeria; stem cell

DOI:  https://doi.org/10.3389/fcell.2025.1546423
J Cosmet Dermatol. 2025 Mar;24(3): e16747

A Functional Skincare Formulation Mixed With Retinyl Propionate, Hydroxypinacolone Retinoate, and Vitamin C on Antiaging and Whitening Han Women in Shanghai, China.

Wei Fang, Jian Qiao, Fan Zhang, Min Chen, Qianjin Bian.

   BACKGROUND: Human skin is remodeled as a result of aging. Retinoids (or retinol derivatives) can intervene in this process, which can be optimally formulated and concentrated by providing maximum antiaging effects with minimal irritation.
AIMS: To determine the optimal ratio of two retinol derivatives hydroxypinacolone retinoate (HPR), retinol propionate (RP), and vitamin C (VitC) in dermal remodeling and preventing skin aging, and to investigate their synergistic antiaging and whitening effects in vitro and in vivo.
METHODS: An in vitro model of human skin fibroblast (HSF) was established to evaluate the cellular viability of VitC and/or RP/HPR treatment. We quantified the expression of genes associated with antiaging and retinol receptors in HSFs treated with VitC and/or RP/HPR. The research was conducted on 120 volunteer women to quantify the antiaging efficacy of functional skincare formulation.
RESULTS: A combination of VitC and RP/HPR at a weight ratio of 40:3 achieved the optimal and safe antiaging performance in vitro. Transcription of aging-associated genes and the release of elastin and senescence-associated secretory phenotypes (SASPs) increased significantly after UV irradiation, whereas VitC and RP/HPR cotreatment can inhibit this increase. The synergistic stimulation of VitC and RP/HPR cotreatment showed higher efficacy in the recovery ability of skin injury.
CONCLUSIONS: Our results indicated the advanced skin antiaging and whitening effects of VitC and RP/HPR cotreatment in vitro and in vivo. A combination of VitC and RP/HPR is a potent strategy to postpone skin aging and improve skin whitening for middle-aged women.
TRIAL REGISTRATION: ClinicalTrials.gov identifier: 2020-LS-023.

Keywords:  aging face; creams; retinyl propionate; whitening agents

DOI:  https://doi.org/10.1111/jocd.16747
Int J Nanomedicine. 2025 ;20 2555-2556

Response to Article "Regenerative Potential Nanomedicine of Adipocyte Stem Cell-Derived Exosomes in Senescent Skin Tissue" [Letter].

Yingjian Tan, Yue Zeng, Rui Li.

DOI: https://doi.org/10.2147/IJN.S522282