1.β-sitosterol, an important component in the fruits of Alpinia oxyphylla Miq., prolongs lifespan of Caenorhabditis elegans by suppressing the ferroptosis pathway.
Junyi LI ; Siyuan CHEN ; Liyao XIE ; Jin WANG ; Ao CHENG ; Shaowei ZHANG ; Jiyu LIN ; Zhihan FANG ; Yirui PAN ; Chonghe CUI ; Gengxin CHEN ; Chao ZHANG ; Li LI
Journal of Southern Medical University 2025;45(8):1751-1757
OBJECTIVES:
To elucidate the anti-aging effect of β-sitosterol (BS), an important component in the fruits of Alpinia oxyphylla Miq., in C. elegans and its regulatory effect on ETS-5 gene to modulate ferroptosis.
METHODS:
C. elegans treated with 10 µg/mL BS were monitored for survival time and changes in body length, motility, and reproductive function. The effect of ETS-5 gene knockdown on survival time of C. elegans was observed, and the changes in fat accumulation and lipid redox homeostasis in the transfected C. elegans were assessed using Oil Red O staining and by detecting MDA levels and the GSH/GSSG ratio. The mRNA expression levels of ferroptosis-related genes (FTN-1, GPX-1 and AAT-9) were detected using qPCR. The effects of BS treatment and ETS-5 knockdown on AAT-9 enzyme activity in C. elegans were examined. The effect of BS on nuclear localization of FEV (the human homolog of ETS-5) was validated in cultured human umbilical venous endothelial cells (HUVECs).
RESULTS:
Both BS treatment and ETS-5 knockdown significantly prolonged the lifespan, promoted lipid accumulation and reduced lipid peroxidation in C. elegans. ETS-5 knockdown resulted in upregulated expressions of the ferroptosis repressors GPX-1, AAT-9 and FTN-1 and increased the GSH/GSSG ratio in C. elegans.
CONCLUSIONS
BS inhibits ferroptosis in C. elegans by suppressing the expression of ETS-5 transcription factor and hence the activity of AAT-9 enzyme, a key gene for ferroptosis, which in turn prolongs the lifespan of C. elegans.
Animals
;
Caenorhabditis elegans/physiology*
;
Ferroptosis/drug effects*
;
Alpinia/chemistry*
;
Sitosterols/pharmacology*
;
Longevity/drug effects*
;
Fruit/chemistry*
;
Humans
2.Factors involved in human healthy aging: insights from longevity individuals.
Fan-Qian YIN ; Fu-Hui XIAO ; Qing-Peng KONG
Frontiers of Medicine 2025;19(2):226-249
The quest to decipher the determinants of human longevity has intensified with the rise in global life expectancy. Long-lived individuals (LLIs), who exceed the average life expectancy while delaying age-related diseases, serve as a unique model for studying human healthy aging and longevity. Longevity is a complex phenotype influenced by both genetic and non-genetic factors. This review paper delves into the genetic, epigenetic, metabolic, immune, and environmental factors underpinning the phenomenon of human longevity, with a particular focus on LLIs, such as centenarians. By integrating findings from human longevity studies, this review highlights a diverse array of factors influencing longevity, ranging from genetic polymorphisms and epigenetic modifications to the impacts of diet and physical activity. As life expectancy grows, understanding these factors is crucial for developing strategies that promote a healthier and longer life.
Humans
;
Healthy Aging/physiology*
;
Longevity/physiology*
;
Epigenesis, Genetic
;
Life Expectancy
;
Exercise
;
Aging/genetics*
;
Diet
;
Aged, 80 and over
3.Constituent and effects of polysaccharides isolated from Sophora moorcroftiana seeds on lifespan, reproduction, stress resistance, and antimicrobial capacity in Caenorhabditis elegans.
Yuan ZHANG ; Dan-Yang MI ; Jin WANG ; Yan-Ping LUO ; Xu YANG ; Shi DONG ; Xing-Ming MA ; Kai-Zhong DONG
Chinese Journal of Natural Medicines (English Ed.) 2018;16(4):252-260
Sophora moorcroftiana (S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious diseases. The present study aimed to investigate the constituent and biological effects of polysaccharides from S. moorcroftiana seeds in Caenorhabditis elegans (C. elegans). Polysaccharides from S. moorcroftiana seeds (SMpol) were extracted with 60% ethanol and constituent was analyzed by GC-MS. SMpol was composed of glucose, galactose and inositol in the molar ratio of 35.7 : 1.3 : 17.0. Synchronized worms were treated with SMpol and then lifespan, motility, reproduction, stress resistance and antimicrobial activity were examined. Compared with the control group, the lifespan was increased to the average of 27.3 days and the number of laying eggs showed a 1.3-fold increase in nematodes treated with SMpol (4 mg·mL). In SMpol (4 mg·mL) treated worms, there was a 1.1-fold increase in 24-h survival of acute heat stress and a 1.6-fold increase in 2-h survival of oxidative stress The colonization of the bacteria in the SMpol treated nematode was significantly lower than that of the untreated group by 68.3%. In vivo studies showed SMpol significantly extended the life span, improved reproduction, increased stress resistance and antimicrobial capacity of C. elegans. In conclusion, those results indicated that the polysaccharides from S. moorcroftiana seeds were involved in a variety of biological activities leading to its modulatory effects on C. elegans which may be developed as a natural supplement agent.
Animals
;
Caenorhabditis elegans
;
drug effects
;
physiology
;
Longevity
;
drug effects
;
Plant Extracts
;
chemistry
;
isolation & purification
;
pharmacology
;
Polysaccharides
;
chemistry
;
isolation & purification
;
pharmacology
;
Reproduction
;
drug effects
;
Seeds
;
chemistry
;
Sophora
;
chemistry
;
Stress, Physiological
;
drug effects
4.C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans.
Lu WANG ; Fei XU ; Guishuan WANG ; Xiaorong WANG ; Ajuan LIANG ; Hefeng HUANG ; Fei SUN
Protein & Cell 2016;7(10):714-721
Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.
Animals
;
Caenorhabditis elegans
;
genetics
;
metabolism
;
Caenorhabditis elegans Proteins
;
genetics
;
metabolism
;
Female
;
Lipid Droplets
;
metabolism
;
Lipid Metabolism
;
physiology
;
Longevity
;
physiology
;
Mutation
;
Oogenesis
;
physiology
5.Sirtuins Function as the Modulators in Aging-related Diseases in Common or Respectively.
Chinese Medical Journal 2015;128(12):1671-1678
Aging
;
genetics
;
metabolism
;
Animals
;
Diabetes Mellitus
;
enzymology
;
metabolism
;
Humans
;
Longevity
;
genetics
;
physiology
;
Neoplasms
;
enzymology
;
metabolism
;
Neurodegenerative Diseases
;
enzymology
;
metabolism
;
Obesity
;
enzymology
;
metabolism
;
Sirtuins
;
genetics
;
metabolism
6.Factors influencing the longevity and replacement frequency of Provox voice prostheses.
Alper YENIGUN ; Sabri Baki EREN ; Murat Haluk OZKUL ; Selahattin TUGRUL ; Aysenur MERIC
Singapore medical journal 2015;56(11):632-636
INTRODUCTIONThis study aimed to assess the factors that influence the longevity and replacement frequency of Provox voice prostheses following their placement.
METHODSThe medical records of 27 patients who received Provox voice prostheses after total laryngectomy and attended follow-up regularly between 1998 and 2012 were retrospectively reviewed. The success rate of the Provox voice prostheses (i.e. whether speech was achieved), quality of speech achieved, number and type of complications encountered, frequency of prostheses replacement and reasons for prostheses replacements were evaluated.
RESULTSAll 27 patients were men and their mean age was 63.0 (range 43-78) years. The mean follow-up period was 60.3 (range 1-168) months. Fluent and understandable speech was achieved in 85.0% of the patients. The mean duration before prosthesis replacement had to be performed was 17.1 (range 1-36) months. The most frequent complication was fluid leakage through the prosthesis. There was a strong positive correlation of 77.1% between the longevity of prostheses and postoperative follow-up duration (r = 0.771; p < 0.01).
CONCLUSIONThe voice prosthesis is a tool that can be delivered in a practical fashion and replaced easily with no serious complications. It is a means by which speech can be restored, with a high success rate, after total laryngectomy. In the present study, we found that postoperative follow-up duration was the most important factor influencing the longevity of the Provox voice prosthesis.
Adult ; Aged ; Female ; Follow-Up Studies ; Humans ; Laryngeal Diseases ; surgery ; Laryngectomy ; Larynx, Artificial ; Longevity ; physiology ; Male ; Middle Aged ; Postoperative Complications ; epidemiology ; Prosthesis Design ; Reoperation ; Retrospective Studies ; Time Factors
7.Role of p66Shc gene in human longevity.
Jun LI ; Jian GUAN ; Ren-Zhi WANG ; Ning WANG
Acta Academiae Medicinae Sinicae 2014;36(6):686-690
The p66Shc gene has emerged as a novel gerontogene affecting health and life during aging. In murine models of aging,a genetic deficiency of the p66Shc gene,which encodes a phosphotyrosine signal adapter protein,extends life span by 30%. p66Shc is a crucial regulator of reactive oxygen species levels and is involved in age-related dysfunctions. UP to now,oxidative stress has been recognized to be involved in human diseases such as high cholesterol,diabetes,and cardiovascular diseases. Further study on the role of p66Shc will facilitate the research of novel disease-targetted drugs and slow down or cure age-related pathologies.
Aging
;
genetics
;
Animals
;
Humans
;
Longevity
;
genetics
;
Mice
;
Oxidative Stress
;
physiology
;
Reactive Oxygen Species
;
metabolism
;
Shc Signaling Adaptor Proteins
;
genetics
8.Effect of linear alkylbenzenesulfonate on the reproductive capacity and life-span of Drosophila melanogaster.
Wenhong ZHAO ; Ding ZHANG ; Chunxian ZHOU ; Chengmei JIANG
Journal of Central South University(Medical Sciences) 2011;36(2):154-158
OBJECTIVE:
To investigate the effect of linear alkylbenzenesulfonate (LAS) on the reproductive capacity and life-span of Drosophila melanogaster.
METHODS:
Drosophila melanogaster images within 8 h after eclosion were collected with ether anesthesia. The female and male of similar size and normal shape and behavior were selected. The Drosophila melanogasters were cultured in the culture medium containing LAS of different densities. We divided the Drosophila melanogaster into 4 groups according to LAS concentrations: a low dose group with LAS 150 mg/kg, a middle dose group with LAS 300 mg/kg,a high dose group with LAS 600 mg/kg, and a control group without LAS, respectively. The changes of the reproductive capacity, median lethal time, mean life-span and max mean life-span of drosophila melanogaster with different doses of LAS were measured and compared with those of the control.
RESULTS:
The pupa numbers of filial generation of Drosophila melanogaster in the low, middle, and high dose groups (85.07%, 84.59% and 71.88%, respectively) were lower than those in the control group (P<0.01). The median lethal time, mean life-span and max mean life-span of Drosophila melanogaster in the low, middle, and high dose groups were shorter than those in the control group (P<0.05). The change of life-span of Drosophila melanogaster in the high dose group was remarkable: the median lethal time of female and male shortened 13 days and 15 days, the mean life-span of female and male shortened 18 days and 14 days, and the max mean life-span of female and male shortened 14 days and 12 days, respectively.
CONCLUSION
LAS has definite toxicity to Drosophila melanogaster, which can degrade the reproductive capacity of Drosophila melanogaster and shorten the life-span of Drosophila melanogaster.
Alkanesulfonic Acids
;
pharmacology
;
toxicity
;
Animals
;
Dose-Response Relationship, Drug
;
Drosophila melanogaster
;
physiology
;
Female
;
Life Expectancy
;
Longevity
;
Male
;
Reproduction
;
drug effects
;
Surface-Active Agents
;
pharmacology
;
toxicity
9.Anti-aging effect of transplantation of mouse fetus-derived mesenchymal stem cells.
Jun LI ; Yuan ZHANG ; Ge-Xiu LIU
Acta Physiologica Sinica 2010;62(1):79-85
To determine the role of allogeneil graft of mesenchymal stem cells in mammalian longevity, mesenchymal stem cells were isolated from BALB/c mouse uterine-incision delivery fetus by two successive density gradient centrifugations, and then were purified and amplified by adherent culture. Identified P1 mesenchymal stem cells were injected (i.v.) through vena caudalis into the 15-month-old female BALB/c mice three times. The mice were evaluated with ultrasoundcardiogram, autopsy, score of cardiac, skin, lung, kidney, colon histopathology and serum total superoxide dismutase activity, maleic dialdehyde content, glutathione peroxidase activity. The results showed that after transplantation, the long-term surviving stem cells were found to be located in many organ tissues with in situ Y chromosomal hybridization dyeing. Median life span was increased in these animals after transplantation. Skin, cardiac, lung, kidney and colon pathology development were delayed. The retrogradation of heart function was attenuated, the increase of heart mass index (the mass of heart/the mass of the body), and serum maleic dialdehyde content, the decrease of spleen mass index (the mass of spleen/the mass of the body), serum total superoxide dismutase activity and glutathione peroxidase activity were reduced three months after transplantation (all P<0.05). These results support the idea that longevity can be enhanced by transplantation of mesenchymal stem cells and reinforce the hypothesis of mesenchymal stem cell as antiager.
Aging
;
physiology
;
Animals
;
Female
;
Fetal Stem Cells
;
transplantation
;
Longevity
;
physiology
;
Mesenchymal Stem Cell Transplantation
;
Mice
;
Mice, Inbred BALB C
;
Random Allocation
10.Longevity of Toxocara cati Larvae and Pathology in Tissues of Experimentally Infected Chickens.
Ahmad ORYAN ; Seyyed Mahmoud SADJJADI ; Shahrzad AZIZI
The Korean Journal of Parasitology 2010;48(1):79-80
This study was conducted to determine the distribution patterns and duration of stay of Toxocara cati larvae in organs of chickens and to investigate chronic phase and potential zoonotic risk of toxocariasis in chickens. Chickens were orally infected with 1,000 embryonated T. cati eggs and necropsied 240 days post-infection. Organs of the chickens were examined at gross and microscopic levels; tissues were digested to recover larvae. Peribronchiolitis with infiltration of lymphocytes, and hyperplasia of bronchiolar associated lymphatic tissues (BALT) and goblet cells, were evident in the lungs of infected chickens. There were mild hemorrhages and infiltration of lymphocytes and a few eosinophils in the meninges. Larvae were recovered from 30% of the exposed chickens. Larvae recovery indicated that T. cati larvae stay alive for at least 240 days in the chicken brain. Therefore, chickens may potentially act as a paratenic host in nature and transfer T. cati larvae to other hosts.
Animals
;
Brain/pathology
;
Chickens
;
Larva/physiology
;
*Longevity
;
Lung/pathology
;
Poultry Diseases/*parasitology/*pathology
;
Toxascariasis/pathology/*veterinary
;
Toxocara/*pathogenicity/*physiology

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