bims-caglex 2025-02-09 papers

bims-caglex

Biomed News

on Cellular aging and life extension

Issue of 2025–02–09
thirty-six papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño

The beneficial effects of curcumin on aging and age-related diseases: from oxidative stress to antioxidant mechanisms, brain health and apoptosis.
Crassifolin A prolongs lifespan and healthspan in Caenorhabditis elegans via activating autophagy.
Ginkgolide B increases healthspan and lifespan of female mice.
The Role and Molecular Pathways of SIRT6 in Senescence and Age-related Diseases.
The transcription factor STAT3 and aging: an intermediate medium.
Chikusetsu saponin IVa attenuates aging by improving autophagy and mitophagy.
HINT1 Suppression Protects Against Age-Related Cardiac Dysfunction by Enhancing Mitochondrial Biogenesis.
Metformin delays the decline in thermogenic function of brown adipose tissue in a mouse model of Hutchinson-Gilford progeria syndrome.
A BCL-xL/BCL-2 PROTAC effectively clears senescent cells in the liver and reduces MASH-driven hepatocellular carcinoma in mice.
Testosterone in long-term sedentary aging males: Effect of antiaging strategies.
In vivo medical imaging for assessing geroprotective interventions in humans.
LncRNA NEAT1-206 regulates autophagy of human umbilical cord mesenchymal stem cells through the WNT5A/Ca2+ signaling pathway under senescence stress.
The state of the art in anti-aging: plant-based phytochemicals for skin care.
Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice.
Macrophage co-culture promotes cell reprogramming and prevents ferroptosis in aging fibroblasts for neurodegeneration therapy.
Therapeutic Reprogramming toward Regenerative Medicine.
A novel microcapsule composite Spherulites Peony Superior Retinol mitigates UVB-induced skin damage in vitro and in vivo.
Young bone marrow transplantation delays bone aging in old mice.
Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial.
A Multi-Component Reaction Peptide Augmenting the Anti-Aging Benefits of Non-Ablative Laser Procedure.
Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation.
Multi-dimensional evidence from the UK Biobank shows the impact of diet and macronutrient intake on aging.
Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.
CircSPG21 ameliorates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells and mitigates intervertebral disc degeneration through the miR-217/SIRT1 axis and mitophagy.
Unlocking the potential of l-α-glycerylphosphorylcholine in the food industry: From safety approvals to market prospects.
The impact of lifestyle factors across the life course on sarcopenia and physical frailty.
Can good sleep quality enhance the benefits of oral collagen supplementation in the prevention of skin aging? A brief report.
Oral Supplementation with the Short-Chain Fatty Acid Acetate Ameliorates Age-Related Arterial Dysfunction in Mice.
Hydrogels empowered mesenchymal stem cells and the derived exosomes for regenerative medicine in age-related musculoskeletal diseases.
Antiaging properties of chlorogenic acid through protein and gene biomarkers in human skin fibroblast cells as photoaging model.
Efficacy and Cellular Mechanism of Biomimetic Marine Adhesive Protein-Based Coating Against Skin Photoaging.
Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation.
Comparison of the effectiveness of protein supplementation combined with resistance training on body composition and physical function in healthy elderly adults: A systematic review and network meta-analysis.
Senolytic compounds reduce epigenetic age of blood samples in vitro.
Alternate-day fasting enhanced weight loss and metabolic benefits over pair-fed calorie restriction in obese mice.
The miR-6779/XIAP axis alleviates IL-1β-induced chondrocyte senescence and extracellular matrix loss in osteoarthritis.

Front Aging Neurosci. 2025 ;17 1533963

The beneficial effects of curcumin on aging and age-related diseases: from oxidative stress to antioxidant mechanisms, brain health and apoptosis.

Ying He, Yongqing Liu, Min Zhang.

  Aging and age-related disease are among the most common and challenging issues worldwide. During the aging process, the accumulation of oxidative stress, DNA damage, telomere dysfunction, and other related changes lead to cellular dysfunction and the development of diseases such as neurodegenerative and cardiovascular conditions. Curcumin is a widely-used dietary supplement against various diseases such as cancer, diabetes, cardiovascular diseases and aging. This agent mediates its effects through several mechanisms, including the reduction of reactive oxygen species (ROS) and oxidative stress-induced damage, as well as the modulation of subcellular signaling pathways such as AMPK, AKT/mTOR, and NF-κB. These pathways are involved in cellular senescence and inflammation, and their modulation can improve cell function and help prevent disease. In cancer, Curcumin can induce apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing ROS production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of nuclear factor kappa B (NF-κB) and cyclooxygenase-2 (COX-2), which are involved in the overexpression of antiapoptosis genes such as Bcl-2. It can also attenuate the regulation of antiapoptosis phosphoinositide 3-kinases (PI3K) signaling and increase the expression of mitogen-activated protein kinases (MAPKs) to induce endogenous production of ROS. Therefore, herein, we aim to summarize how curcumin affect different epigenetic processes (such as apoptosis and oxidative stress) in order to change aging-related mechanisms. Furthermore, we discuss its roles in age-related diseases, such as Alzheimer, Parkinson, osteoporosis, and cardiovascular diseases.

Keywords:  age-related diseases; aging; curcumin; nano-curcumin; signaling pathways

DOI:  https://doi.org/10.3389/fnagi.2025.1533963
J Ethnopharmacol. 2025 Jan 30. pii: S0378-8741(25)00082-0. [Epub ahead of print]342 119399

Crassifolin A prolongs lifespan and healthspan in Caenorhabditis elegans via activating autophagy.

Wenyu Dai, Lifeng Deng, Chenyang He, Xiaoxia Fu, Jing Liu, Guo-Cai Wang, Jing Yang, Yu-Bo Zhang, Fei Xiao, Qin-Li Wan.

   ETHNOPHARMACOLOGICAL RELEVANCE: The root of Croton crassifolius Geiseler (C. crassifolius), commonly known as "Jiguxiang" in traditional Chinese medicine, is globally recognized for its ethnomedical applications in treating a spectrum of diseases. Crassifolin A (CA), a diterpenoid compound extracted from the roots of C. crassifolius, exhibits anti-herpes simplex virus (HSV), anti-viral and anti-angiogenic properties.
AIM OF THE REVIEW: This study aimed to explore the effects of CA on aging and the mechanisms involved.
MATERIALS AND METHODS: Utilizing Caenorhabditis elegans (C. elegans) as a model organism, we conducted a comprehensive survival analysis and evaluated aging-related phenotypes, including the period of fast body movement and body bending rates. To elucidate the molecular mechanisms of CA's impact on aging, we employed a multifaceted approach, including reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, and fluorescence quantification of transgenic reporter strains.
RESULTS: Our findings demonstrated that CA significantly prolonged both the lifespan and healthspan of C. elegans. The survival benefits conferred by CA were found to correlate with the activation of several key aging-related signaling pathways, including insulin/insulin-like signaling pathway (IIS), dietary restriction (DR) pathway, and germline signaling pathway. Engagement of these pathways led to the activation of transcription factors DAF-16/FOXO, SKN-1/NRF2, HSF-1 and HLH-30/TFEB, as well as the nuclear receptor DAF-12. Consequently, this activation cascade prompted an upregulation of autophagy, a cellular process associated with the maintenance of cellular homeostasis and longevity.
CONCLUSION: Our study delineates novel mechanisms underlying anti-aging strategies, establishing a conceptual framework for the exploitation and advancement of traditional Chinese medicinal herbs as potential therapeutic agents in the fight against aging and its associated pathologies.

Keywords:  Caenorhabditis elegans; Crassifolin A (CA); Croton crassifolius; Longevity

DOI:  https://doi.org/10.1016/j.jep.2025.119399
Nat Aging. 2025 Jan 31.

Ginkgolide B increases healthspan and lifespan of female mice.

Chien-Wei Lee, Belle Yu-Hsuan Wang, Shing Hei Wong, Yi-Fan Chen, Qin Cao, Allen Wei-Ting Hsiao, Sin-Hang Fung, Yu-Fan Chen, Hao-Hsiang Wu, Po-Yu Cheng, Zong-Han Chou, Wayne Yuk-Wai Lee, Stephen Kwok Wing Tsui, Oscar Kuang-Sheng Lee.

Various anti-aging interventions show promise in extending lifespan, but many are ineffective or even harmful to healthspan. Ginkgolide B (GB), derived from Ginkgo biloba, reduces aging-related morbidities such as osteoporosis, yet its effects on healthspan and longevity have not been fully understood. In this study, we found that continuous oral administration of GB to female mice beginning at 20 months of age extended median survival and median lifespan by 30% and 8.5%, respectively. GB treatment also decreased tumor incidence; enhanced muscle quality, physical performance and metabolism; and reduced systemic inflammation and senescence. Single-nucleus RNA sequencing of skeletal muscle tissue showed that GB ameliorated aging-associated changes in cell type composition, signaling pathways and intercellular communication. GB reduced aging-induced Runx1+ type 2B myonuclei through the upregulation of miR-27b-3p, which suppresses Runx1 expression. Using functional analyses, we found that Runx1 promoted senescence and cell death in muscle cells. Collectively, these findings suggest the translational potential of GB to extend healthspan and lifespan and to promote healthy aging.

DOI: https://doi.org/10.1038/s43587-024-00802-0
Adv Biol (Weinh). 2025 Feb 06. e2400469

The Role and Molecular Pathways of SIRT6 in Senescence and Age-related Diseases.

Yi Lu, Junye Yang, Qiuju Wu, Xiaobo Wang.

  SIRT6 is a NAD+-dependent histone deacetylase with crucial roles in controlling DNA damage repair, telomere homeostasis, oxidative stress, autophagy, and other cellular processes, and it has long been recognized as a longevity-associated protein. This review details its anti-aging-related mechanisms. First, SIRT6 facilitates DNA repair pathways and maintains genome stability by deacetylating histone H3 at K56, K9, and K18 residues, in addition to participating in DNA damage repair through mono-ADP-ribosylation and other mechanisms. Second, SIRT6 preserves telomere integrity and mitigates cellular senescence by reducing oxidative stress-induced damage through the regulation of reactive oxygen species (ROS), inhibition of inflammation, and other pathways. Furthermore, SIRT6 promotes autophagy, slowing cellular senescence via the modulation of various signaling pathways, including AMPK, IGF-Akt-mTOR, H133Y, IL-1β, and mitochondrial autophagy-related proteins. Finally, SIRT6 regulates multiple signaling pathways, such asNF-κB, FOXO, and AMPK, to counteract the aging process. This review particularly delves into the interplay between SIRT6 and various diseases, including tumors, cardiovascular diseases (e.g., atherosclerosis, heart failure), metabolic diseases (e.g., type 2 diabetes, dyslipidemia, gluconeogenesis, osteoporosis), and neurodegenerative diseases (e.g., Alzheimer's disease). Moreover, recent advancements in SIRT6-regulated compounds (e.g., C3G, BZBS, Fisetin, FNDC5, Lycorine hydrochloride, and Ergothioneine) are discussed as potential therapeutic agents for these mediated diseases.

Keywords:  SIRT6; mechanisms of senescence; senescence; senescence‐related diseases; signaling pathway

DOI:  https://doi.org/10.1002/adbi.202400469
Biogerontology. 2025 Feb 07. 26(2): 55

The transcription factor STAT3 and aging: an intermediate medium.

Min Shi, Honyu Li, Runyu Liang, Haiyan Lin, Qiang Tang.

  Aging is a physiological/pathological process accompanied by progressive impairment of cellular function, leading to a variety of aging-related diseases. STAT3 is one of the core regulatory factors of aging. It is involved in body metabolism, development and senescence, cell apoptosis and so on. During the aging process, the changes of growth factors and cytokines will cause the activation of STAT3 to varying degrees, regulate the inflammatory pathways related to aging, regulate body inflammation, mitochondrial function, cell aging and autophagy to regulate and influence the aging process. Drugs targeting STAT3 can treat senescence related diseases. This review summarizes the role of STAT3 signaling factors in the pathogenesis of aging, including mitochondrial function, cellular senescence, autophagy, and chronic inflammation mediated by inflammatory pathways. Finally, the key regulatory role of STAT3 in senescence related diseases is emphasized. In summary, we reveal that drug development and clinical application targeting STAT3 is one of the key points in delaying aging and treating aging-related diseases in the future.

Keywords:  Aging mechanism; Aging-related diseases; STAT3

DOI:  https://doi.org/10.1007/s10522-025-10193-3
Free Radic Biol Med. 2025 Jan 31. pii: S0891-5849(25)00074-7. [Epub ahead of print]230 17-32

Chikusetsu saponin IVa attenuates aging by improving autophagy and mitophagy.

Jing-Zhi Wan, Cheng-Quan Li, Ying-Na Li, Ao-Zhong Li, Qi-Long Yang, Meng Kang, Jia-Hao Cao, Hui-Jie Ran, Qi-Ling Liu, Yi Wan, Song Zhai, Miao-Miao Xi, Hai-Feng Tang, Xu-Jun Qin, Ka Bian.

  Chikusetsu saponin IVa (CHS) is an essential active triterpenoid saponin found in various medicinal herbs, such as Aralia taibaiensis, Panax japonicus, and Aralia elata. While multiple health benefits have been documented, the effect of CHS on aging remains unclear. By employing the D-galactose-induced aging mice and the replicative senescence of primary mouse embryonic fibroblasts (MEFs) as the aging models, we found that CHS significantly attenuated aging both in vitro and in vivo. RNA sequencing analysis revealed that CHS greatly improved autophagy and mitophagy. Corresponding to the improved mitophagy, CHS remarkably reduced mitochondrial ROS and enhanced mitochondrial respiratory function. Mitophagy inhibition and Atg 7 genetic knockout (KO) almost abolished the anti-aging effect of CHS. AMPK pathway was activated during the attenuation of aging by CHS treatment, and a specific AMPK inhibitor reversed the induction of mitophagy and autophagy, as well as the attenuation of aging by CHS. Molecular docking data indicated AMPK as the direct binding target of CHS. In conclusion, our study initially demonstrates that CHS exhibits a potent anti-aging effect both in vitro and in vivo. CHS may directly bind to AMPK and activate the AMPK-dependent pathway to enhance autophagy and mitophagy, thereby reducing mitochondrial ROS and improving mitochondrial respiratory function, contributing to the anti-aging effect. These findings offer a new clue for the promising application of CHS in the improvement of aging and aging-related diseases in the future.

Keywords:  Anti-aging; Chikusetsu saponin IVa (CHS); Mitophagy; Reactive oxygen species (ROS)

DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.01.055
Mol Metab. 2025 Feb 03. pii: S2212-8778(25)00014-6. [Epub ahead of print] 102107

HINT1 Suppression Protects Against Age-Related Cardiac Dysfunction by Enhancing Mitochondrial Biogenesis.

Michio Sato, Tsuyoshi Kadomatsu, Jun Morinaga, Yuya Kinoshita, Daisuke Torigoe, Haruki Horiguchi, Sumio Ohtsuki, Shuji Yamamura, Ryoko Kusaba, Takanori Yamaguchi, Goro Yoshioka, Kimi Araki, Tomohiko Wakayama, Keishi Miyata, Koichi Node, Yuichi Oike.

  Cardiac function declines with age, impairing exercise tolerance and negatively impacting healthy aging. Here, we observed inactivation of mitochondrial biogenesis in hearts of aged mice and a reduction in mitochondrial mass. We also showed that activity of the BAF chromatin remodeling complex is repressed by HINT1, whose expression in heart increases with age, leading to decreased transcription of Tfam, which promotes mitochondrial biogenesis. Interestingly, calorie restriction (CR) not only suppressed age-related declines in cardiac function and mitochondrial biogenesis but blocked concomitant increases in cardiac HINT1 protein levels and maintained Tfam transcription. Furthermore, expression of the lncRNA Caren, which inhibits Hint1 mRNA translation, decreased with age in heart, and CR suppressed this effect. Finally, decreased HINT1 expression due to Caren overexpression antagonized age-related declines in mitochondrial biogenesis, ameliorating age-related cardiac dysfunction, exercise intolerance, and exercise-induced cardiac damage and subsequent death of mice. These data suggest overall that the Caren-HINT1-mitochondrial biogenesis axis represents an important mechanism of CR-induced resistance to cardiac aging.

Keywords:  Calorie restriction; Cardiac aging; Heart failure; Mitochondrial biogenesis

DOI:  https://doi.org/10.1016/j.molmet.2025.102107
Exp Gerontol. 2025 Feb 06. pii: S0531-5565(25)00030-0. [Epub ahead of print]201 112702

Metformin delays the decline in thermogenic function of brown adipose tissue in a mouse model of Hutchinson-Gilford progeria syndrome.

Xin Xiang, Yuyue Feng, Hongcheng Li, Wenbo Li, Jia Li, Zhu Xia, Hua Pang, Zhengjie Wang.

  Brown adipose tissue (BAT) is the primary site for non-shivering thermogenesis in the body and plays a crucial role in maintaining core body temperature. However, its function gradually declines with age. To mitigate the age-related decline in BAT thermogenic capacity, we treated progeroid mice with metformin to investigate the potential mechanisms by which metformin can slow the reduction in BAT thermogenic function. We found that progeroid mice, after receiving metformin treatment, showed significant improvement in the senescent state of brown adipocytes through the activation of SIRT1, and effectively reduced mitochondrial oxidative stress. Additionally, metformin slowed the age-related decline in UCP1 expression levels in brown adipose tissue, thereby maintaining the thermogenic capacity of the progeroid mice. Moreover, metformin reduced inflammatory responses around senescent cells, further improving the overall senescent state of the tissue. These findings suggest that metformin can slow down the aging process in brown adipose tissue by targeting SIRT1, thereby enhancing its thermogenic capacity.

Keywords:  Brown adipose tissue; Metformin; SIRT1; Senescence; Thermogenic function

DOI:  https://doi.org/10.1016/j.exger.2025.112702
Nat Aging. 2025 Jan 31.

A BCL-xL/BCL-2 PROTAC effectively clears senescent cells in the liver and reduces MASH-driven hepatocellular carcinoma in mice.

Yang Yang, Natacha Jn-Simon, Yonghan He, Chunbao Sun, Peiyi Zhang, Wanyi Hu, Tian Tian, Huadong Zeng, Sreenivasulu Basha, Araceli S Huerta, Lu-Zhe Sun, Xian-Ming Yin, Robert Hromas, Guangrong Zheng, Liya Pi, Daohong Zhou.

Accumulation of senescent cells (SnCs) plays a causative role in many age-related diseases and has also been implicated in the pathogenesis and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Senolytics that can selectively kill SnCs have the potential to be developed as therapeutics for these diseases. Here we report the finding that 753b, a dual BCL-xL/BCL-2 proteolysis-targeting chimera (PROTAC), acts as a potent and liver-tropic senolytic. We found that treatment with 753b selectively reduced SnCs in the liver in aged mice and STAM mice in part due to its sequestration in the liver. Moreover, 753b treatment could effectively reduce the progression of MASLD and the development of hepatocellular carcinoma (HCC) in STAM mice even after the mice developed substantial metabolic dysfunction-associated steatohepatitis (MASH) and hepatic fibrosis. These findings suggest that BCL-xL/BCL-2 PROTACs have the potential to be developed as therapeutics for MASLD to reduce MASH-driven HCC.

DOI: https://doi.org/10.1038/s43587-025-00811-7
Physiol Int. 2025 Feb 06.

Testosterone in long-term sedentary aging males: Effect of antiaging strategies.

Khaled A Abdel-Sater.

  Physical activity can provide health benefits if done regularly and of sufficient duration and intensity. The World Health Organization recommends adults do 150-300 min of moderate-intensity activity per week, 75-150 min of vigorous-intensity activity, or an equivalent combination.Physical inactivity is the fourth leading cause of early death globally, with 31% of the world's population not getting enough physical activity. Aging is defined by rapid decline in physical activity, loss of mobility, and premature morbidity.Low testosterone levels in men decline from 30 to 40 years of age, and this continues until death. Antiaging strategies, such as caloric restriction, balanced diet, regular exercise, weight management, diabetes control, and smoking cessation can prevent and treat aging-related diseases. Exercise significantly boosts testosterone production, with levels varying based on type, frequency, volume, intensity, and duration. It increases muscle steroidogenesis, total testosterone, and free testosterone in the elderly. Testosterone replacement therapy in elderly men improves physical function, strength, protein synthesis, cholesterol, bone density, sexual desire, erectile function, and overall cognition. However, some studies suggest dehydroepiandrosterone supplementation may provide health improvements without negative effects, potentially reversing arterial aging and reducing the risk of cardiovascular diseases. Senolytic therapeutics focus on cellular senescence, and stem cell transplantation investigates the therapeutic potential of older stem cells.

Keywords:  elderly men; physical activity; sedentary life; testosterone; testosterone replacement therapy

DOI:  https://doi.org/10.1556/2060.2024.00486
Geroscience. 2025 Feb 06.

In vivo medical imaging for assessing geroprotective interventions in humans.

Jonas E Svensson, Martin Schain, Pontus Plavén-Sigray.

  There is a growing interest in developing drugs with a general geroprotective effect, aimed at slowing down aging. Several compounds have been shown to increase the lifespan and reduce the incidence of age-related diseases in model organisms. Translating these results is challenging, due to the long lifespan of humans. To address this, we propose using a battery of medical imaging protocols that allow for assessments of age-related processes known to precede disease onset. These protocols, based on magnetic resonance imaging, positron emission-, computed-, and optical coherence tomography, are already in use in drug development and are available at most modern hospitals. Here, we outline how an informed use of these techniques allows for detecting changes in the accumulation of age-related pathologies in a diverse set of physiological systems. This in vivo imaging battery enables efficient screening of candidate geroprotective compounds in early phase clinical trials, within reasonable trial durations.

Keywords:  Age-related disease; Biomarker; CT; Drug development; Geroprotection; Imaging; MRI; OCT; PET

DOI:  https://doi.org/10.1007/s11357-025-01514-y
Noncoding RNA Res. 2025 Apr;11 234-248

LncRNA NEAT1-206 regulates autophagy of human umbilical cord mesenchymal stem cells through the WNT5A/Ca2+ signaling pathway under senescence stress.

Weili Wang, Yongyu Wang, Chunchun Duan, Wenjing Tian, Liyang Gao.

  Stem cells are crucial for maintaining bodily stability, but their regenerative abilities decline with age. This decline is marked by reduced proliferation and differentiation capacities of stem cells, as well as exhaustion of the stem cell pool. The accumulation of aged mesenchymal stem cells (MSCs) can reduce the tissue regeneration, but the molecular mechanisms influencing MSCs aging remain unclear. Moreover, collecting MSCs from elderly individuals is not suitable for observing the early response of MSCs to senescence stress, and the factors involved in early senescence remain unclear. In our previous study, we established a fast MSC aging model using D-galactose. We discovered that, while not affecting the "stemness" markers of mesenchymal stem cells, the expression of LncRNA NEAT1-206 was notably increased during the early stages of aging induction (within 4 days). And LncRNA NEAT1-206 was observed to be localized in the cytoplasmic matrix due to enhanced nuclear export. We found that the LncRNA NEAT1-206 could trigger autophagy through the WNT5A/Ca2+ signaling pathway, thereby decreasing senescence markers and enhancing the osteogenic differentiation of MSCs. This study elucidated the role that LncRNA NEAT1-206 as a potential key factor in conferring resistance to D-galactose-induced cell senescence at the early stage and promoting the osteogenic differentiation of MSCs. This study may provide a foundational understanding for delaying the MSCs aging process.

Keywords:  Autophagy; Cell senescence; LncRNA NEAT1-206; Mesenchymal stem cells; WNT5A/Ca2+ signaling pathway

DOI:  https://doi.org/10.1016/j.ncrna.2024.12.013
Immun Ageing. 2025 Jan 31. 22(1): 5

The state of the art in anti-aging: plant-based phytochemicals for skin care.

Merve Tomas, Deniz Günal-Köroğlu, Senem Kamiloglu, Tugba Ozdal, Esra Capanoglu.

  Phytochemicals help mitigate skin aging by scavenging free radicals, modulating key enzymatic pathways, and promoting the skin's structural integrity. Carotenoids, vitamins, essential fatty acids, and phenolic compounds work by acting as antioxidants, inhibiting enzymes like hyaluronidase, collagenase, and elastase, which degrade skin structure, and reducing levels of inflammatory markers (IL-6, IL-8, etc.) and matrix metalloproteinases (MMP-1, MMP-2) linked to aging. Recent research highlights that plant-based phytochemicals can improve skin elasticity, reduce hyperpigmentation, prevent the breakdown of important skin proteins, and support wound healing, making them valuable components for skin care and treatments. This review explores the multifaceted roles of phytochemicals in maintaining and improving skin health, highlighting their mechanisms of action and potential in skin anti-aging innovations.

Keywords:  Alkoloids; Anti-aging; Carotenoids; Fatty acids; Phytochemicals; Polyphenols; Saponins; Skin care

DOI:  https://doi.org/10.1186/s12979-025-00498-9
Geroscience. 2025 Feb 04.

Fecal microbiota transplant from long-living Ames dwarf mice alters the microbial composition and biomarkers of liver health in normal mice.

Sarah A Ashiqueali, Natalie Hayslip, Diptaraj S Chaudhari, Augusto Schneider, Xiang Zhu, Blazej Rubis, Corey E Seavey, Md Tanjim Alam, Ridwan Hussein, Sarah A Noureddine, Ewelina Golusinska-Kardach, Pawel Pazdrowski, Hariom Yadav, Michal M Masternak.

  Aging is associated with intestinal dysbiosis, a condition characterized by diminished microbial biodiversity and inflammation. This leads to increased vulnerability to extraintestinal manifestations such as autoimmune, metabolic, and neurodegenerative conditions thereby accelerating mortality. As such, modulation of the gut microbiome is a promising way to extend healthspan. In this study, we explore the effects of fecal microbiota transplant (FMT) from long-living Ames dwarf donors to their normal littermates, and vice versa, on the recipient gut microbiota and liver transcriptome. Importantly, our previous studies highlight differences between the microbiome of Ames dwarf mice relative to their normal siblings, potentially contributing to their extended lifespan and remarkable healthspan. Our findings demonstrate that FMT from Ames dwarf mice to normal mice significantly alters the recipient's gut microbiota, potentially reprogramming bacterial functions related to healthy aging, and changes the liver transcriptome, indicating improved metabolic health. Particularly, the microbiome of Ames dwarf mice, characterized by a higher abundance of beneficial bacterial families such as Peptococcaceae, Oscillospiraceae, and Lachnospiraceae, appears to play a crucial role in modulating these effects. Alongside, our mRNA sequencing and RT-PCR validation reveals that FMT may contribute to the significant downregulation of p21, Elovl3, and Insig2, genes involved with cellular senescence and liver metabolic pathways. Our data suggest a regulatory axis exists between the gut and liver, highlighting the potential of microbiome-targeted therapies in promoting healthy aging. Future research should focus on functional validation of altered microbial communities and explore the underlying biomolecular pathways that confer geroprotection.

Keywords:  Aging; Gut; Healthspan; Liver; Metabolism; Microbiome; Senescence; Transcriptome

DOI:  https://doi.org/10.1007/s11357-025-01539-3
J Mol Med (Berl). 2025 Feb 01.

Macrophage co-culture promotes cell reprogramming and prevents ferroptosis in aging fibroblasts for neurodegeneration therapy.

Lunjie Ma, Fei Fang, Haonan Wang, Ping Zhao, Hongchi Yu, Xiaoheng Liu.

  Ferroptosis, a form of programmed cell death associated with lipid peroxidation and iron dependency, plays a critical role in affecting neuronal function in the aging-related neurodegenerative diseases. Macrophages, influenced by these changes, contribute significantly to the progression of aging nerve diseases. Induced neuronal reprogramming is an advanced technology, which can direct convert somatic cells, such as fibroblasts, into neurons, and offers a promising approach for drug screening aimed at correcting ferroptosis and combating aging-related nerve diseases. However, the efficiency of this reprogramming process remains a significant challenge. In this study, we aimed to manipulate macrophage phenotypes to enhance the direct conversion of fibroblasts into neurons. Specifically, we sought to correct ferroptosis through screening natural compounds using aged fibroblasts and utilizing macrophages to promote induced neuronal (iN) reprogramming. Our findings demonstrate that M2 macrophages effectively promote the direct reprogramming of fibroblasts into iNs. In a novel macrophage-fibroblast co-culture system, M2 macrophages facilitate iN reprogramming by reducing fibroblast adhesion forces and promoting asymmetric cell division. Furthermore, we discovered that manipulating matrix stiffness can induce polarization of macrophages towards the M2 phenotype, thereby enhancing fibroblast reprogramming into iNs. To facilitate these findings, we developed a mechano-cue-based drug screening chip, where soft hydrogels induced and maintained the phenotype of M2 macrophages and effectively promoted cell reprogramming. Using a combinatorial approach with 36 such chips, we screened natural compounds for their anti-aging properties, focusing on reversing fibroblast aging and inducing their conversion into neuronal cells. Notably, Vitexin, an apigenin flavone glycoside with a role as a platelet aggregation inhibitor, emerged as a promising candidate to achieve our therapeutic goals. This study highlights the potential of macrophage-mediated modulation of fibroblast reprogramming as a strategy to address ferroptosis-induced neuronal dysfunction in aging-related nerve diseases. KEY MESSAGE: This study highlights the potential of macrophage-mediated modulation of fibroblast reprogramming as a strategy to address ferroptosis-induced neuronal dysfunction in aging-related nerve diseases.

Keywords:  Aging; Cell reprogramming; Drug screening; Ferroptosis; Lab-on-chip; Macrophage

DOI:  https://doi.org/10.1007/s00109-025-02518-z
Chem Rev. 2025 Feb 05.

Therapeutic Reprogramming toward Regenerative Medicine.

Sheng Ding.

Therapeutic reprogramming represents a transformative paradigm in regenerative medicine, developing new approaches in cell therapy, small molecule drugs, biologics, and gene therapy to address unmet medical challenges. This paradigm encompasses the precise modulation of cellular fate and function to either generate safe and functional cells ex vivo for cell-based therapies or to directly reprogram endogenous cells in vivo or in situ for tissue repair and regeneration. Building on the discovery of induced pluripotent stem cells (iPSCs), advancements in chemical modulation and CRISPR-based gene editing have propelled a new iterative medicine paradigm, focusing on developing scalable, standardized cell therapy products from universal starting materials and enabling iterative improvements for more effective therapeutic profiles. Beyond cell-based therapies, non-cell-based therapeutic strategies targeting endogenous cells may offer a less invasive, more convenient, accessible, and cost-effective alternative for treating a broad range of diseases, potentially rejuvenating tissues and extending healthspan.

DOI: https://doi.org/10.1021/acs.chemrev.4c00332
Photochem Photobiol. 2025 Feb 05.

A novel microcapsule composite Spherulites Peony Superior Retinol mitigates UVB-induced skin damage in vitro and in vivo.

Jiejun Han, Rongyue Gong, Yuankun Liu, Tiangui Gong, Bin Wang, Laidi Zhang, Jiayue Chen.

  Skin serves as our outermost barrier, protecting our bodies from various environmental damages. Increasing research has revealed that UVB is a primary factor for extrinsic aging. This study explored the role of a novel microcapsule composite Spherulites Peony Superior Retinol (SPSR) on skin damage induced by UVB. SPSR exhibited a capacity to eliminate UVB-induced ROS. By measurement of cyclobutane pyrimidine dimers (CPD) and comet assay, the results implied that SPSR mitigates DNA damage from oxidative damage caused by UVB. In addition, UVB radiation typically leads to an increase in inflammatory factors within the skin. Decreased gene expressions of interleukin-1α and TNF-α have been observed in HaCaT cells. Moreover, a decreased gene expression of extracellular matrix (ECM)-related protein, including fibronectin (FN1), Col1A1, and Col3A1 caused by UVB was mitigated by SPSR. Furthermore, the clinical trials with 30 volunteers confirmed the significant relief and antiwrinkle effects of the cosmetic formulation containing 0.1% SPSR. These findings implied the promising potential of SPSR as a comprehensive solution for combating the detrimental effects of UVB exposure and maintaining skin health.

Keywords:  DNA damage repair; Spherulites Peony Superior Retinol; UVB; fibroblast; mast cell

DOI:  https://doi.org/10.1111/php.14078
Exp Gerontol. 2025 Feb 04. pii: S0531-5565(25)00032-4. [Epub ahead of print] 112704

Young bone marrow transplantation delays bone aging in old mice.

Lina Abu-Nada, Younan Liu, Faez Al-Hamed, Bouchra Ouliass, Magali Millecamps, Simon D Tran, Guylaine Ferland, Vahab D Soleimani, Faleh Tamimi Marino, Monzur Murshed.

  Recent discoveries have shown that systemic manipulation, such as parabiosis, blood exchange, and young plasma transfer, can counteract many hallmarks of aging. This rejuvenation effect has been attributed to circulatory factors produced by cells from both hematopoietic and non-hematopoietic lineages. However, the specific involvement of bone marrow (BM) or hematopoietic cells in producing such factors and their effects on aging is still unclear. We developed a model of aged mice with transplanted young or old BM cells and assessed the impact on the aging process, specifically on energy metabolism and bone metabolism. The donor BM cell engraftment in the aged mice was confirmed by flow cytometry using a transplanted cell-specific marker (green fluorescent protein). Energy metabolism was assessed using Oxymax indirect calorimetry system after 3 months of transplantation. Tibiae and L3-L4 vertebrae were analyzed using micro-CT, A three-point bending test and bone histomorphometry. Moreover, bone marrow proteome was assessed using proteomics and blood serum/plasma was collected and analyzed using Luminex. Our results showed that while the effect on energy metabolism was insignificant, rejuvenating the BM through young bone marrow transplantation reversed age-associated low bone mass traits in old mice. Specifically, young bone marrow transplantation improved bone trabecular microarchitecture both in tibiae and vertebrae of old mice and increased the number of osteoblasts and osteoclasts compared to old bone marrow transplantation. In conclusion, young bone marrow cells may represent a future therapeutic strategy for age-related diseases such as osteoporosis. The findings of this study provide important insights into our understanding of aging.

Keywords:  Aging; Bone; Bone marrow transplantation

DOI:  https://doi.org/10.1016/j.exger.2025.112704
Nat Aging. 2025 Feb 03.

Individual and additive effects of vitamin D, omega-3 and exercise on DNA methylation clocks of biological aging in older adults from the DO-HEALTH trial.

Heike A Bischoff-Ferrari, Stephanie Gängler, Maud Wieczorek, Daniel W Belsky, Joanne Ryan, Reto W Kressig, Hannes B Stähelin, Robert Theiler, Bess Dawson-Hughes, René Rizzoli, Bruno Vellas, Laure Rouch, Sophie Guyonnet, Andreas Egli, E John Orav, Walter Willett, Steve Horvath.

While observational studies and small pilot trials suggest that vitamin D, omega-3 and exercise may slow biological aging, larger clinical trials testing these treatments individually or in combination are lacking. Here, we report the results of a post hoc analysis among 777 participants of the DO-HEALTH trial on the effect of vitamin D (2,000 IU per day) and/or omega-3 (1 g per day) and/or a home exercise program on four next-generation DNA methylation (DNAm) measures of biological aging (PhenoAge, GrimAge, GrimAge2 and DunedinPACE) over 3 years. Omega-3 alone slowed the DNAm clocks PhenoAge, GrimAge2 and DunedinPACE, and all three treatments had additive benefits on PhenoAge. Overall, from baseline to year 3, standardized effects ranged from 0.16 to 0.32 units (2.9-3.8 months). In summary, our trial indicates a small protective effect of omega-3 treatment on slowing biological aging over 3 years across several clocks, with an additive protective effect of omega-3, vitamin D and exercise based on PhenoAge.

DOI: https://doi.org/10.1038/s43587-024-00793-y
J Drugs Dermatol. 2025 Feb 01. 24(2): 188-195

A Multi-Component Reaction Peptide Augmenting the Anti-Aging Benefits of Non-Ablative Laser Procedure.

Kun Mark Qian, Michael Kaminer, I-Chien Liao, Janet Wangari-Olivero, Jyotsna Paturi, Ying Chen, Patricia Brieva, Rabije Cekovic, Charbel Bouez, Qian Zheng.

BACKGROUND: Laser resurfacing is one of the most popular aesthetic procedures that address a wide range of skin conditions and overall skin rejuvenation. To reduce downtime and improve the clinical efficacy of the procedures, it is important to design post-procedure care routines to complement them. Towards fulfilling that consumer need, a peptide synthesized from multi-component reaction (MCP) has been developed.
AIMS:  The objective of this study is to investigate the functionalities of MCP as a regenerative active that enhances the healing kinetics and anti-aging performance following non-ablative fractional laser resurfacing procedures.
METHODS:  To fulfill the objective, a single-center, split-face design, double-blinded, randomized clinical study was conducted. Study participants received a full face non-ablative fractional laser procedure followed by treatment with two topical products, MCP formula or Aquaphor Healing Ointment®or AHO (Beiersdorf Inc, Wilton, CT) as a standard of care topical agent. Both products were applied immediately after the laser procedure and continued two times daily for 28 days. Clinical evaluation and expert grading of healing and aging, instrument measurement of skin barrier function, optical coherence tomography and standardized digital imaging were performed.
RESULTS:  Clinical evaluation results showed that the MCP formula promoted post-procedure skin healing at a comparable level as Aquaphor Healing Ointment®. However, the MCP formula demonstrated faster kinetics and enhanced level of improvement in multiple anti-aging parameters when compared with the benchmark control. Results from this clinical study demonstrate that the use of MCP formula post non-ablative fractional laser treatment is efficacious in promoting skin healing and enhancing the anti-aging benefits provided by the procedure. J Drugs Dermatol. 2025;24(2):188-195. doi:10.36849/JDD.8066R1.

DOI: https://doi.org/10.36849/JDD.8066
Front Cardiovasc Med. 2024 ;11 1506360

Epigallocatechin gallate (EGCG) modulates senescent endothelial cell-monocyte communication in age-related vascular inflammation.

Sarvatit Patel, Kai Ellis, Corey A Scipione, Jason E Fish, Kathryn L Howe.

  Aging significantly affects intercellular communication between vascular endothelial cells (ECs) and hematopoietic cells, leading to vascular inflammation and age-associated diseases. This study determined how senescent ECs communicate with monocytes, whether extracellular vesicles (EVs) released from senescent ECs affect monocyte functions, and investigated the potential for epigallocatechin-3-gallate (EGCG), a flavonoid in green tea, to reverse these effects. Human umbilical vein endothelial cells (HUVECs) were treated with Etoposide (10 µM, 24 h) to induce senescence, followed by EGCG (100 µM, 24 h) treatment to evaluate its potential as a senotherapeutic agent. The interaction between ECs and monocytes was analyzed using a co-culture system and direct treatment of monocytes with EC-derived EVs. EGCG reduced senescence-associated phenotypes in ECs, as evidenced by decreased senescence-associated (SA)-β-Gal activity and reversal of Etoposide-induced senescence markers. Monocytes co-cultured with EGCG-treated senescent ECs showed decreased pro-inflammatory responses compared to those co-cultured with untreated senescent ECs. Additionally, senescent ECs produced more EVs than non-senescent ECs. EVs from senescent ECs enhanced lipopolysaccharide (LPS)-induced pro-inflammatory activation of monocytes, whereas EVs from EGCG-treated senescent ECs mitigated this activation, maintaining monocyte activation at normal levels. Our findings reveal that EGCG confers anti-senescent effects via modulation of the senescent EC secretome (including EVs) with the capacity to modify monocyte activation. These findings suggest that EGCG could act as a senotherapeutic agent to reduce vascular inflammation related to aging.

Keywords:  aging; cardiovascular disease; endothelial senescence; endothelial-monocyte communication; epigallocatechin gallate (EGCG); extracellular vesicles; inflammation

DOI:  https://doi.org/10.3389/fcvm.2024.1506360
Commun Med (Lond). 2025 Feb 04. 5(1): 36

Multi-dimensional evidence from the UK Biobank shows the impact of diet and macronutrient intake on aging.

Chen Zhu, Youfa Wang, Xiaosong Yang, Qiran Zhao, Wenyan Xu, Xiaolu Wang, Yanjun Liang, Qihui Chen, Shenggen Fan.

BACKGROUND: The role of diet in aging is crucial, yet research findings on how specific diets influence human aging remain inconsistent. Understanding the relationship between dietary factors and aging could inform interventions to promote healthier aging outcomes.
METHODS: We analyzed data from the UK Biobank baseline survey and a 24-hour dietary assessment survey to investigate the association between diet and aging. The study examined 18 individual food intakes, 6 dietary patterns, 3 macronutrient intakes, and 3 dietary quality scores. High-dimensional Fixed Effects (HDFE) models were used to assess associations between dietary factors and aging measures, including telomere length, phenotypic age, and brain grey/white matter volumes. Multivariable Mendelian Randomization (MVMR) was employed to explore causal links between macronutrient consumption and aging outcomes.
RESULTS: Our results show that healthier diets are generally associated with improved aging outcomes from HDFE analyses. Plant-based food consumption correlates with increased telomere length and reduced phenotypic age, while animal-based food intake is linked to adverse aging effects. MVMR results confirm the causal benefits of carbohydrate intake, including reductions in phenotypic age (β = -0.0025; 95% CI = [-0.0047, -0.0003]; p = 0.0253) and increases in whole-brain grey matter volume (β = 0.0262; 95% CI = [0.007, 0.046]; p = 0.0087). The latter association remains significant after multiple testing correction.
CONCLUSIONS: This study underscores the significant role of diet in biological aging and provides robust evidence for the benefits of carbohydrate intake in promoting healthier aging. These findings highlight the potential of dietary interventions to improve aging-related outcomes.

DOI: https://doi.org/10.1038/s43856-025-00754-5
Int J Biol Sci. 2025 ;21(3): 910-939

Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.

Xin Yu, Wei Pei, Bei Li, Shengrong Sun, Wenge Li, Qi Wu.

  Aging is associated with a decline in immune function, termed immunosenescence, which compromises host defences and increases susceptibility to infections and cancer. Physical exercise is widely recognized for its myriad health benefits, including the potential to modulate the immune system. This review explores the bidirectional relationship between immunosenescence and physical exercise, focusing on their interplay in shaping antitumor immunity. We summarize the impact of aging on innate and adaptive immune cells, highlighting alterations that contribute to immunosenescence and cancer development. We further delineate the effects of exercise on immune cell function, demonstrating its potential to mitigate immunosenescence and enhance antitumor responses. We also discuss the implications of immunosenescence for the efficacy of immunotherapies, such as immune checkpoint inhibitors and adoptive T cell therapy, and explore the potential benefits of combining exercise with these interventions. Collectively, this review underscores the importance of understanding the complex relationship between immunosenescence, physical exercise, and antitumor immunity, paving the way for the development of innovative strategies to improve cancer outcomes in the aging population.

Keywords:  Exercise; Immunosenescence; Immunotherapy; Tumor Immunity

DOI:  https://doi.org/10.7150/ijbs.100948
Stem Cell Res Ther. 2025 Feb 07. 16(1): 49

CircSPG21 ameliorates oxidative stress-induced senescence in nucleus pulposus-derived mesenchymal stem cells and mitigates intervertebral disc degeneration through the miR-217/SIRT1 axis and mitophagy.

Yongbo Zhang, Sheng Yang, Xuan You, Zhengguang Li, Liuyang Chen, Rui Dai, Hua Sun, Liang Zhang.

   BACKGROUND: The microenvironment of intervertebral disc degeneration (IVDD) is characterized by oxidative stress, leading to the senescence of nucleus pulposus-derived mesenchymal stem cells (NPMSCs). The purpose of this study was to investigate the competitive endogenous RNA mechanism involved in the senescence of NPMSCs induced by tert-butyl hydroperoxide (TBHP).
METHODS: Bioinformatic analysis identified differentially expressed circRNAs. Interactions among circSPG21, miR-217, and the NAD-dependent protein deacetylase sirtuin-1 (SIRT1) were validated through dual-luciferase assays, RNA fluorescence in situ hybridization and RNA immune precipitation. β-Gal staining, EdU staining, Western blotting, JC-1 assays, cell cycle analysis, and quantitative reverse transcription PCR (RT‒qPCR) were used to examine the functions of these molecules in TBHP-induced senescent NPMSCs. The therapeutic effects of circSPG21 were evaluated in a rat IVDD model.
RESULTS: CircSPG21 expression was significantly decreased in both human and rat IVDD tissues, whereas miR-217 was upregulated and SIRT1 was downregulated. Overexpression of circSPG21 alleviated NPMSC senescence by reducing P21 and P53 levels and restoring mitophagy through Parkin. The protective effects of circSPG21 were mediated through the miR-217/SIRT1 axis, as SIRT1 knockdown attenuated these benefits. CircSPG21 also ameliorated disc degeneration in the IVDD rat model, highlighting its potential as a therapeutic target.
CONCLUSION: CircSPG21 reduces oxidative stress-induced NPMSC senescence through the miR-217/SIRT1 axis and mitophagy, providing new insights into IVDD and identifying circSPG21 as a potential therapeutic target for disc degeneration.

Keywords:  Intervertebral disc degeneration; Mitophagy; Nucleus pulposus-derived mesenchymal stem cell; Senescence; ceRNA

DOI:  https://doi.org/10.1186/s13287-025-04180-1
Compr Rev Food Sci Food Saf. 2025 Mar;24(2): e70117

Unlocking the potential of l-α-glycerylphosphorylcholine in the food industry: From safety approvals to market prospects.

Jun Cao, Erzheng Su.

  With the exacerbation of global population aging, age-related neurodegenerative disorders have been posing an increasing public health concern. l-α-Glycerylphosphorylcholine (l-α-GPC) has demonstrated significant therapeutic potential for mental health-related disorders and possesses promising market prospects. Recently, l-α-GPC has been successively approved as a new food resource in Canada (2023) and in China (2024). These policies pointed out the recognized safety and utility of l-α-GPC. The utilization of l-α-GPC in dietary supplements and health foods could be a convenient option for early intervention strategies to potentially delay or mitigate the progression of neurodegenerative disorders. Additionally, other unique nutritional benefits of l-α-GPC have been highlighted, further expanding its application in food industry. Encouraged by the policy incentives, there is likely to be a new upsurge in the research interest surrounding l-α-GPC. To fully capitalize on these emerging opportunities, we present a comprehensive review of l-α-GPC. The chemical properties, pharmacological characteristics, safety assessments, and preparation methods of l-α-GPC were summarized. A brief outlook on the future perspectives and unsolved challenges was also proposed.

Keywords:  l‐α‐glycerylphosphorylcholine (l‐α‐GPC); method; new food resource; production; safety assessment

DOI:  https://doi.org/10.1111/1541-4337.70117
Curr Opin Clin Nutr Metab Care. 2025 Jan 23.

The impact of lifestyle factors across the life course on sarcopenia and physical frailty.

Daphne Zihui Yang, Joanne Kua, Wee Shiong Lim.

PURPOSE OF REVIEW: Muscle health helps maintain locomotor capacity, a key component of intrinsic capacity, which is required for healthy ageing. Sarcopenia is characterized by the age-related decline in muscle mass and strength leading to impaired physical performance, and has been described as a biological substrate of physical frailty. Both sarcopenia and physical frailty share phenotypic features of weakness and slowness, lead to common adverse outcomes, and have potential for reversal through early identification and intervention. The purpose of this review is to present recent evidence for the impact of lifestyle interventions across the life course on sarcopenia and physical frailty.
RECENT FINDINGS: Resistance exercise alone or combined with balance and aerobic training as part of a multicomponent exercise program and high-quality diets incorporating adequate protein remain the mainstay of treatment for sarcopenia and physical frailty. Reducing sedentary time and increasing physical activity, adherence to Mediterranean diet, increasing vegetable and caffeinated beverage intake, cardiovascular risk factor modification, improving sleep hygiene and depressive symptoms may also contribute to slowing down age-related decline in muscle health.
SUMMARY: Lifestyle interventions such as physical activity, diet, sleep and mental health are effective against sarcopenia and physical frailty. Targeting lifestyle modifications in early to midlife may retard further decline in locomotor capacity and optimize intrinsic capacity of older persons, reducing the risk of sarcopenia, physical frailty and their attendant negative health outcomes.

DOI: https://doi.org/10.1097/MCO.0000000000001111
Arch Dermatol Res. 2025 Feb 06. 317(1): 340

Can good sleep quality enhance the benefits of oral collagen supplementation in the prevention of skin aging? A brief report.

Ellen M S Xerfan, Maingredy Rodrigues Souza, Anamaria S Facina, Sergio Tufik, Monica L Andersen.

   INTRODUCTION: Collagen is essential to skin structure and integrity, and it is continually degraded with aging due to higher oxidative stress. Sleep deprivation accelerates skin aging and reduces collagen production. Good sleep may be a potential adjuvant to the efficacy of oral supplementation with collagenic peptides for the skin.
OBJECTIVES: To summarize clinical benefits to the skin of collagen intake, and consider the role of sleep in its effectiveness.
METHODS: Studies in the PubMed database that reported the effects of oral administration of collagen peptides were searched; and studies presenting the association of collagen metabolism with sleep.
RESULTS: A total of 1117 articles were initially identified; 66 were reviewed in full. Most involved women at third or fourth decade of life. Daily collagen doses ranged from 1 to 10 g, with intervention periods lasting from 4 to 8 weeks. Consistent improvements in skin elasticity, hydration, and wrinkle reduction were observed, with increase in dermal density and structural proteins. Collagen combined with vitamins, minerals, and antioxidants provided additional benefits, including improved skin radiance and reduced pore size. Studies on sleep and skin indicated that poor sleep can impair skin hydration, increase transepidermic water loss, and reduce elasticity, highlighting the potential role of sleep in maximizing the benefits of collagen supplementation.
CONCLUSIONS: Hydrolyzed collagen supplementation, particularly at 2.5 g/day, has shown benefits for skin after 4 weeks of use. Sleep quality may enhance these effects by supporting immune function and reducing oxidative stress. Further studies are needed on sleep's role in enhancing collagen supplementation benefits.

Keywords:  Collagen; Collagen supplementation; Extracellular matrix; Skin aging; Sleep; Sleep deprivation

DOI:  https://doi.org/10.1007/s00403-025-03860-5
Aging Biol. 2024 ;pii: 20240033. [Epub ahead of print]2

Oral Supplementation with the Short-Chain Fatty Acid Acetate Ameliorates Age-Related Arterial Dysfunction in Mice.

Abigail G Longtine, Nathan T Greenberg, Antonio Gonzalez, Alexandra Lindquist, Nicholas S VanDongen, Sophia A Mahoney, Gibraan Rahman, Zachary S Clayton, Brian P Ziemba, Katelyn R Ludwig, Michael E Widlansky, Rob Knight, Douglas R Seals, Vienna E Brunt.

Adverse changes in the gut microbiome with aging are an emerging mediator of arterial dysfunction, which contributes to cardiovascular disease (CVD) development. We investigated the therapeutic potential of enhancing the bioavailability of gut-derived short-chain fatty acids (SCFAs; produced from dietary fiber) for improving age-related arterial dysfunction. We performed gut microbial whole-genome sequencing in young (3 months) versus old (24 months) male C57BL/6N mice to explore changes in bacterial taxonomic abundance and functional pathways with aging and relations to arterial function. We then supplemented young and old mice with the SCFA acetate in drinking water versus controls and versus a high-fiber diet for 8-10 weeks to test the effects of these interventions on vascular function and explore potential mechanisms. Of the various differences in the gut microbiomes of old mice, lower SCFA-producing capacity (taxonomic abundance and functional pathways) stood out as a key feature related to worse arterial function after adjusting for age. Acetate supplementation and a high-fiber diet reversed ~30% of the age-related increase in aortic pulse wave velocity (stiffness) and fully restored carotid artery endothelium-dependent dilation (endothelial function) to young levels. Acetate and a high-fiber diet reduced age-related increases in systemic inflammation. We also found that improvements in endothelial function were likely mediated by suppressed early growth response-1 signaling using innovative siRNA-based knockdown in isolated arteries. There were no effects of the interventions in young mice. Acetate supplementation was comparably effective for ameliorating arterial dysfunction with aging as a high-fiber diet and thus shows promise for reducing CVD risk in older adults.

DOI: https://doi.org/10.59368/agingbio.20240033
Pharmacol Res. 2025 Jan 30. pii: S1043-6618(25)00043-X. [Epub ahead of print]213 107618

Hydrogels empowered mesenchymal stem cells and the derived exosomes for regenerative medicine in age-related musculoskeletal diseases.

Lixin Liu, Siwen Chen, Yantao Song, Longwei Cui, Yiman Chen, Jiangli Xia, Yibo Fan, Liqun Yang, Lina Yang.

  As the population ages, musculoskeletal diseases (MSK) have emerged as a significant burden for individuals, healthcare systems, and social care systems. Recently, regenerative medicine has exhibited vast potential in age-related MSK, with mesenchymal stromal cells (MSCs) and their derived exosomes (Exos) therapies showing distinct advantages. However, these therapies face several limitations, including issues related to ensuring stability and effective distribution within the body. Hydrogels, acting as an ideal carrier, can enhance the therapeutic effects and application range of MSCs and Exos derived from MSCs (MSC-Exos). Therefore, this review comprehensively summarizes the application progress of MSCs and MSC-Exos combined with hydrogels in age-related MSK disease research. It aims to provide a detailed perspective, showcasing the functional enhancement of MSCs and MSC-Exos when incorporated into hydrogels. Additionally, this review explores their potential and challenges in treating age-related MSK diseases, offering references for future research directions and potential innovative strategies.

Keywords:  Aging; Exosome; Hydrogels; Mesenchymal stem cells; Musculoskeletal Diseases

DOI:  https://doi.org/10.1016/j.phrs.2025.107618
Res Pharm Sci. 2024 Dec;19(6): 746-753

Antiaging properties of chlorogenic acid through protein and gene biomarkers in human skin fibroblast cells as photoaging model.

Ermi Girsang, Chrismis N Ginting, I Nyoman Ehrich Lister, Wahyu Widowati, Afif Yati, Hanna Sari Widya Kusuma, Rizal Azis.

   Background and purpose: Chlorogenic acid (CA) is a natural chemical that promises antiaging activity against photoaging skin damage. This research examined CA activities in mitigating skin photoaging.
Experimental approach: UV-exposed human skin fibroblast cells were subjected to CA at 6.25, 12.5, and 25 μg/mL. The protein levels of cell secretion, such as cyclooxygenase (COX)-2, nitric oxide (NO), and interleukin (IL)-6 were measured using ELISA and colorimetry methods. Meanwhile, the mRNA expressions of glutathione peroxidase (GPX)-1, tissue inhibitor metalloproteinase (TIMP)-1, matrix metalloproteinase (MMP)-1, caspase (CASP)-3, CASP-8, and fibroblast growth factor (FGF)-2 were quantified using the qRT-PCR method.
Findings/Results: CA treatment reduced inflammatory and aging biomarkers. CA at 6.25 μg/mL lowered NO, COX-2, and IL-6 levels to 89.44 μmol/L, 8.10 ng/mL, and 62.75 pg/mL, respectively. CA at 25 μg/mL resulted in the most significant down-regulation of MMP-1, CASP-3, and CASP-8 genes' expression (3.27, 1.25, and 3.59, respectively). Furthermore, treatment with CA at 25 µg/mL demonstrated the most notable activity in up-regulating antioxidant markers, specifically GPX-1, and extracellular matrix (ECM) integrity markers, including TIMP-1 and FGF-2 genes' expression.
Conclusion and implications: CA imposes its anti-aging activity by decreasing inflammatory and aging biomarkers, and increasing cellular antioxidant and ECM integrity.

Keywords:  Antiaging; Chlorogenic acid; Fibroblast; Ultraviolet; qRT-PCR

DOI:  https://doi.org/10.4103/RPS.RPS_177_22
Adv Healthc Mater. 2025 Feb 03. e2402019

Efficacy and Cellular Mechanism of Biomimetic Marine Adhesive Protein-Based Coating Against Skin Photoaging.

Bo Xue.

  Skin photoaging is a problem worldwide, clinically often accompanied by collagen decline, increased wrinkles, loss of skin elasticity, structurally weakened skin, and other complications, which urgently demand effective treatment strategies. The biosafety and efficacy of single-function therapies for repairing skin photoaging are still challenging for clinical medicine today. At present, numerous studies report that the wet adhesive proteins driven from marine organisms play a critical role in the biomedical material field, particularly in aquatic environments. In this study, a natural recombinant protein-based coating from scallop byssal protein is prepared to investigate the efficacy and cellular mechanism in accelerating the repair of UVB-induced photoaging in a mouse model. In vitro experiments demonstrate the safety of the coating and its efficacy in enhancing cell adhesion, spreading, proliferation, and migration. Additionally, the coating effectively scavenges reactive oxygen species, promotes the expression of cell adhesion molecules and anti-apoptotic proteins, and inhibits inflammatory responses. In animal tests, the coating exhibited remarkable adsorption properties, showing significant potential for in situ regenerative therapy, as evidenced by its ability to protect against UVB-induced skin photoaging and oxidative stress. These findings suggest that Sbp9Δ coating provides a simple, safe, and innovative strategy for treating skin photoaging.

Keywords:  coating; reactive oxygen species scavenging; scallop byssal protein; skin photoaging; tissue repair

DOI:  https://doi.org/10.1002/adhm.202402019
Cell Metab. 2025 Feb 01. pii: S1550-4131(25)00023-3. [Epub ahead of print]

Ergothioneine improves healthspan of aged animals by enhancing cGPDH activity through CSE-dependent persulfidation.

Dunja Petrovic, Luke Slade, Yiorgos Paikopoulos, Davide D'Andrea, Nevena Savic, Ana Stancic, Jan Lj Miljkovic, Thibaut Vignane, Maria Kyriaki Drekolia, Dusan Mladenovic, Nikola Sutulovic, Alice Refeyton, Milica Kolakovic, Vladimir M Jovanovic, Jasmina Zivanovic, Marko Miler, Valentina Vellecco, Vincenzo Brancaleone, Mariarosaria Bucci, Alva M Casey, ChakShun Yu, Siva Swapna Kasarla, Karl William Smith, Ayten Kalfe-Yildiz, Martin Stenzel, Antonio Miranda-Vizuete, Roland Hergenröder, Prasad Phapale, Olivera Stanojlovic, Ivana Ivanovic-Burmazovic, Marija Vlaski-Lafarge, Sofia-Iris Bibli, Michael P Murphy, Vesna Otasevic, Milos R Filipovic.

DOI: https://doi.org/10.1016/j.cmet.2025.01.023
J Nutr. 2025 Jan 29. pii: S0022-3166(25)00024-0. [Epub ahead of print]

Comparison of the effectiveness of protein supplementation combined with resistance training on body composition and physical function in healthy elderly adults: A systematic review and network meta-analysis.

Haiping Tian, Wanwan Qiao, Xianxiu Wen.

   BACKGROUND: The global population of individuals over 65 is expected to reach 426 million by 2050. Aging is associated with a progressive loss of muscle mass, strength, and function, leading to sarcopenia and adverse outcomes such as physical disability and increased mortality. Interventions such as resistance training and protein supplementation have shown promise in mitigating these effects.
OBJECTIVE: To determine the comparative effectiveness of protein supplementation, resistance training, and their combination on body composition and physical function in healthy older adults through a network meta-analysis.
METHODS: We conducted a systematic review and network meta-analysis following PRISMA guidelines and registered in PROSPERO (CRD42021226561). We included randomized controlled trials comparing protein supplementation, resistance training, and their combination in participants aged 50 years or older. Data were extracted from PubMed, Web of Science, Embase, and Cochrane Library. The risk of bias was assessed using the Cochrane Collaboration Risk of Bias Tool.
RESULTS: A total of 38 randomized controlled trials involving 2,610 participants were included. The combined intervention of protein supplementation and resistance training significantly improved lean body mass (SMD, 0.44; 95% CI, 0.05 to 0.95) compared to protein supplementation alone. The combined intervention also showed significant improvements in muscle mass (SMD, 1.49; 95% CI, 0.11 to 2.67). The combined intervention (SMD, 2.74, 95% CI 0.76 to 4.74) and resistance training alone (SMD, 2.53, 95% CI 0.29 to 4.84) significantly improved muscle strength compared to controls. The combined intervention (SMD, 4.98, 95% CI 2.72 to 7.17) and resistance training alone (SMD, 4.52, 95% CI 2.30 to 6.64) significantly improved physical function compared to protein supplementation alone.
CONCLUSION: Combining exercise and protein supplementation is the most effective for improving muscle mass, strength, and physical function in older adults. This approach should be considered for enhancing physical health in this population. Future large-scale trials are necessary to confirm these findings.

Keywords:  Aged; Body Composition; Network Meta-analysis; Physical Function; Protein Supplementation; Resistance Training

DOI:  https://doi.org/10.1016/j.tjnut.2025.01.017
NPJ Aging. 2025 Feb 04. 11(1): 6

Senolytic compounds reduce epigenetic age of blood samples in vitro.

Vithurithra Tharmapalan, Miriam Du Marchie Sarvaas, Michael Bleichert, Martina Wessiepe, Wolfgang Wagner.

Senolytic drugs raise the expectation that they can specifically eliminate a subset of senescent cells in a given tissue. In this study, we have exemplarily analyzed if a 3-day treatment of human blood samples in vitro would reduce age-associated biomarkers, with a particular focus on epigenetic age-predictions. Of eight tested compounds, JQ1, RG7112, nutlin-3a, and AMG232 reduced epigenetic age, indicating that this approach may be useful in drug screening for senolytic compounds.

DOI: https://doi.org/10.1038/s41514-025-00199-z
Obesity (Silver Spring). 2025 Feb 04.

Alternate-day fasting enhanced weight loss and metabolic benefits over pair-fed calorie restriction in obese mice.

Hadia Nawaz, Haneul Lee, Sumin Kang, Hayoon Kim, Wooki Kim, Gwang-Woong Go.

OBJECTIVE: Both alternate-day fasting (ADF) and calorie restriction (CR) are effective weight loss strategies. However, most individuals find it difficult to adhere to CR. Furthermore, CR can induce an excessive loss of not only fat but also muscle mass. This study aimed to compare the effects of ADF and pair-feeding (PF) CR on metabolic pathways underlying obesity in mice with high-fat diet (HFD)-induced obesity.
METHODS: Male C57BL/6N Tac mice (n = 10 per group) were fed an HFD for 8 weeks to establish a diet-induced obesity model. Mice were then continued on the HFD with either alternate-day access to food or PF for the next 8 weeks. We measured body weight, adiposity, plasma biomarkers, and molecular mechanisms involving lipolysis and autophagy.
RESULTS: Both ADF and PF resulted in comparable weight and fat loss. Compared with PF, ADF showed a significant reduction in liver weight and hepatic triglyceride levels. ADF significantly increased plasma ketone body levels and white adipose tissue lipolysis. Compared with PF, ADF tended to activate autophagy elongation and autophagosome formation, which were insignificant.
CONCLUSIONS: These findings indicated that ADF is a promising intervention for metabolic diseases, potentially due to its superior efficacy in promoting ketogenesis and lipolysis compared with PF.

DOI: https://doi.org/10.1002/oby.24211
Animal Model Exp Med. 2025 Feb 04.

The miR-6779/XIAP axis alleviates IL-1β-induced chondrocyte senescence and extracellular matrix loss in osteoarthritis.

Zongchao Li, Aonan Dai, Xiaoxiang Fang, Kexing Tang, Kun Chen, Peng Gao, Jingyue Su, Xin Chen, Shengwu Yang, Zhenhan Deng, Liangjun Li.

   BACKGROUND: Osteoarthritis (OA) is a long-term degenerative joint disease worsening over time. Aging and chondrocyte senescence contribute to OA progression. MicroRNAs have been confirmed to regulate different cellular processes. They contribute to OA pathology and may help to identify novel biomarkers and therapies for OA.
METHODS: This study used bioinformatics and experimental investigations to analyze and validate differentially expressed miRNAs in OA that might affect chondrocyte apoptosis and senescence.
RESULTS: miR-6779 was found to be significantly down-regulated in OA. Seventy-six of the predicted and miR-6779 targeted genes and the OA-associated disease genes overlapped, and these were enriched in cell proliferation, cell apoptosis, and cell cycle. miR-6779 overexpression remarkably attenuated IL-1β effects on chondrocytes by reducing MMP3 and MMP13 levels, promoting cell apoptosis, suppressing cell senescence, and increasing caspase-3, caspase-9 and reducing P16 and P21 levels. miR-6779 targeted inhibition of X-linked inhibitor of apoptosis protein (XIAP) expression. XIAP knockdown partially improved IL-1β-induced chondrocyte senescence and dysfunction. Lastly, when co-transfected with a miR-6779 agomir, the XIAP overexpression vector partially attenuated the effects of miR-6779 overexpression on chondrocytes; miR-6779 improved IL-1β-induced senescence and dysfunction in chondrocytes through targeting XIAP.
CONCLUSION: miR-6779 is down-regulated, and XIAP is up-regulated in OA cartilage and IL-1β-treated chondrocytes. miR-6779 inhibits XIAP expression, thereby promoting senescent chondrocyte cell apoptosis and reducing chondrocyte senescence and ECM loss through XIAP.

Keywords:  X‐linked inhibitor of apoptosis protein; chondrocyte; miR‐6779; osteoarthritis; senescence

DOI:  https://doi.org/10.1002/ame2.12529