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.Effect of Garcinia binucao crude leaf extract supplementation on lifespan of Drosophila melanogaster chronically exposed to alcohol
Joanne Jennifer E. Tan ; Ourlad Alzeus G. Tantengco ; Nicholas Robert C. Tan ; Clyde E. Silverio ; Ana Denise V. Sison ; Joseph P. Sta. Maria Jr. ; Karol Ina G. Tablante ; Joyce Gillian A. Tiam-Lee ; Maria Concepcion C. Sison ; Paul Mark B. Medina
Acta Medica Philippina 2024;58(5):52-56
Background:
Consumption and abuse of alcohol remains a significant cause of concern worldwide. Furthermore, there is evidence of the association between chronic alcohol use and reduced life expectancy.
Objectives:
To study the effects of Garcinia binucao extract (GBE) supplementation on lifespan of Drosophila
melanogaster, in the presence or absence of chronic alcohol exposure.
Methods:
D. melanogaster was mass cultured and given GBE supplementation in high (1 mg/mL) and low (200 µg/mL) sublethal doses. D. melanogaster flies were divided into groups - with and without chronic alcohol exposure, and their respective lifespans were monitored.
Results:
In D. melanogaster without alcohol exposure, mean lifespan was highest in the control flies (38.15 days), followed by high-dose GBE (34.42 days), low-dose GBE (33.24 days), and DMSO (22.29 days). In D. melanogaster chronically exposed to alcohol, the longest mean lifespan was observed in flies treated with high-dose GBE (33.80 days), followed by low-dose GBE (33.63 days), the DMSO group (30.30), and the control group (29.65 days), but the differences were not statistically significant. Comparing groups with and without chronic alcohol exposure, the mean lifespan of the control group chronically exposed to alcohol significantly decreased by 9.51 days (p < 0.05). In GBE treatment groups, mean lifespan significantly decreased by 0.82 days in high-dose set-up (p < 0.05), and significantly increased by 0.39 days in the low-dose set-up (p < 0.05) upon chronic alcohol exposure.
Conclusion
Garcinia binucao extract supplementation ameliorated the observed reduction in lifespan of Drosophila melanogaster chronically exposed to alcohol.
Drosophila melanogaster
;
Longevity
4.Changes and clinical significance of erythrocyte lifespan in megaloblastic anemia.
De Peng WU ; Jun BAI ; Song Lin CHU ; Zheng Dong HAO ; Xiao Jia GUO ; Lian Sheng ZHANG ; Li Juan LI
Chinese Journal of Internal Medicine 2023;62(6):688-692
Objective: To investigate the lifespan of erythrocytes in megaloblastic anemia (MA) patients. Methods: A prospective cohort study analysis. Clinical data from 42 MA patients who were newly diagnosed at the Department of Hematology, Lanzhou University Second Hospital from January 2021 to August 2021 were analyzed, as were control data from 24 healthy volunteers acquired during the same period. The carbon monoxide breath test was used to measure erythrocyte lifespan, and correlations between erythrocyte lifespan and laboratory test indexes before and after treatment were calculated. Statistical analysis included the t-test and Pearson correlation. Results: The mean erythrocyte lifespan in the 42 newly diagnosed MA patients was (49.05±41.60) d, which was significantly shorter than that in the healthy control group [(104.13±42.62) d; t=5.13,P=0.001]. In a vitamin B12-deficient subset of MA patients the mean erythrocyte lifespan was (30.09±15.14) d, and in a folic acid-deficient subgroup it was (72.00±51.44) d, and the difference between these two MA subsets was significant (t=3.73, P=0.001). The mean erythrocyte lifespan after MA treatment was (101.28±33.02) d, which differed significantly from that before MA treatment (t=4.72, P=0.001). In MA patients erythrocyte lifespan was positively correlated with hemoglobin concentration (r=0.373), and negatively correlated with total bilirubin level (r=-0.425), indirect bilirubin level (r=-0.431), and lactate dehydrogenase level (r=-0.504) (all P<0.05). Conclusions: Erythrocyte lifespan was shortened in MA patients, and there was a significant difference between a vitamin B12-deficient group and a folic acid-deficient group. After treatment the erythrocyte lifespan can return to normal. Erythrocyte lifespan is expected to become an informative index for the diagnosis and treatment of MA.
Humans
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Longevity
;
Clinical Relevance
;
Prospective Studies
;
Erythrocytes
;
Anemia, Megaloblastic
;
Folic Acid
;
Bilirubin
;
Vitamins
5.Charting Normative Brain Variability Across the Human Lifespan.
Yongbin WEI ; Han ZHANG ; Yong LIU
Neuroscience Bulletin 2023;39(2):362-364
7.Association between serum lysophosphatidylcholine level and elderly health index in older people from longevity areas of Guangxi Province.
Heng Shuo LIU ; Zhu WU ; Rui Yue YANG ; Guan Zhou CHEN ; Ying LI ; Qi ZHOU ; Hui Ping YUAN ; Ze YANG ; Liang SUN
Chinese Journal of Preventive Medicine 2023;57(5):649-653
Objective: To investigate the relationship between serum lysophosphatidylcholine (LPC) level and the health index of the elderly. Methods: A total of 251 subjects were selected from the 2016 baseline survey of the Yongfu Longevity Cohort in Guangxi Province among whom 66, 63 and 122 were in the young and middle-aged group (≤59 years old), the young group (60-89 years old) and the longevity group (≥90 years old), respectively. Demographic data were collected and related indicators of height, weight, blood pressure and lipid metabolism were measured. The cognitive and physical functions of the elderly were assessed by the results of the simple mental state scale and the daily living activity scale to construct the health index of the elderly. The serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 were determined by liquid chromatography-tandem mass spectrometry, and the differences among different ages and health status groups were compared. The logistic regression model was used to analyze the relationship between the serum LPC level and the health index of the elderly. Results: With the increase in age, the proportion of female subjects increased, and the rate of smoking and drinking decreased. BMI, TC, TG, LDL-C, diastolic blood pressure, and the four LPCs levels decreased with the increase of age, and systolic blood pressure levels increased with the increase of age (all P values<0.05). There was no significant difference in HDL-C levels among age groups (P>0.05). With the decline of health status in the elderly, serum levels of LPC16∶0, LPC18∶0, LPC18∶1 and LPC18∶2 showed a downward trend (all P values<0.001). After adjusting for age and gender, only LPC18∶0 was associated with the health status in old age [OR (95%CI): 0.48 (0.25-0.92)]. For every 1 standard deviation (16.87 nmol/L) increase in serum LPC18∶0 concentration, the risk of poor health status in old age decreased by 52%. Conclusion: Serum LPC18∶0 was associated with the health status in old age independent of age and sex.
Aged
;
Middle Aged
;
Humans
;
Female
;
Aged, 80 and over
;
Lysophosphatidylcholines
;
Risk Factors
;
China
;
Longevity
;
Surveys and Questionnaires
;
Triglycerides
8.Cold stress reduces lifespan and mobility of C. elegans by mediating lipid metabolism disorder and abnormal stress.
Hao SHI ; Chao ZHANG ; Jia Min ZHAO ; Yi Wen LI ; Yun Jia LI ; Jun Jie LI ; Zhi Yun ZENG ; Lei GAO
Journal of Southern Medical University 2022;42(8):1159-1165
OBJECTIVE:
To investigate the changes of lipid metabolism and stress response of adult C.elegans exposed to non-freezing low temperature and explore the possible mechanism.
METHODS:
The survival rate and activity of adult C.elegans cultured at 20℃ or 4℃ were observed.Lipid metabolism of the cultured adult C.elegans was evaluated using oil red O staining and by detecting the expressions of the genes related with lipid metabolism.The effects of low temperature exposure on stress level of adult C.elegans were evaluated using mitochondrial fluorescence staining and by detecting the expression levels of stress-related genes and antioxidant genes at both the mRNA and protein levels.
RESULTS:
The lifespan and activity of adult C.elegans exposed to low temperature were significantly reduced with decreased lipid accumulation (P < 0.05) and decreased expressions of genes related with fatty acid synthesis and metabolism (fat-5, fat-6, fat-7, fasn-1, nhr-49, acs-2 and aco-1;P < 0.01).Cold stress significantly increased the expressions of heat shock proteins hsp-70 and hsp16.2(P < 0.05) but lowered the number of mitochondria (P < 0.0001) and the expressions of atfs-1, sod-2, sod-3 and gpx-1(P < 0.05).Knockout of fat-5, nhr-49 or both fat-5 and fat-6 obviously enhanced the sensitivity of C.elegans to cold stress as shown by further reduced activity (P < 0.05) and reduced survival rate at 24 h (P < 0.0001) under cold stress.
CONCLUSION
Exposure to a low temperature at 4℃ results in lowered lipid metabolism of adult C.elegans accompanied by a decreased mitochondrial number and quality control ability, which triggers high expressions of stress-related genes and causes reduction of antioxidant capacity, thus callsing lowered activity and reduced lifespan of C.elegans.
Animals
;
Antioxidants/metabolism*
;
Caenorhabditis elegans
;
Caenorhabditis elegans Proteins/genetics*
;
Cold-Shock Response
;
Lipid Metabolism
;
Lipid Metabolism Disorders
;
Longevity/genetics*
9.Low-dose chloroquine treatment extends the lifespan of aged rats.
Wei LI ; Zhiran ZOU ; Yusheng CAI ; Kuan YANG ; Si WANG ; Zunpeng LIU ; Lingling GENG ; Qun CHU ; Zhejun JI ; Piu CHAN ; Guang-Hui LIU ; Moshi SONG ; Jing QU ; Weiqi ZHANG
Protein & Cell 2022;13(6):454-461
10.A prospective cohort study of the influence of positive/negative effectivity on the mortality risk of the Chinese elderly.
Journal of Peking University(Health Sciences) 2022;54(2):255-260
OBJECTIVE:
To explore the influence of positive/negative effectivity on the mortality risk of the Chinese elderly.
METHODS:
Using the latest four surveys data of Chinese longitudinal healthy longevity survey in 2008, 2012, and 2014, as well as 2018 and selecting 10 993 elderly people who were aged 65 and above as research objects, this paper compared the positive/negative effectivity status and differences of the elderly in different gender and age groups. And then this paper analyzed the effect of positive/negative effectivity on elderly people' s mortality risk by constructing Cox proportional hazards model.
RESULTS:
Compared with the female elderly, the male elderly had lower negative effectivity and higher positive effectivity. With the increase of age, the negative effectivity of the elderly increased, while the positive effectivity decreased. The results showed that after adjusting for the basic demographic characteristics, health status and living habits of the respondents in the baseline survey, in the positive effectivity dimension, "clean preference" (HR=0.922, 95%CI: 0.889-0.956), "autonomy" (HR=0.933, 95%CI: 0.914-0.952) and "sense of youth" (HR=0.948, 95%CI: 0.927-0.969), had a protective effect on the mortality risk of the elderly, while in the dimension of "open-minded view", there was no significant difference in the mortality risk of the elderly with different answers. In the negative effecti-vity dimension, "tension and fear" (HR=1.039, 95%CI: 1.014-1.065), "loneliness" (HR=1.053, 95%CI: 1.029-1.079) and "uselessness" had a harmful effect on the mortality risk of the elderly. The more positive effectivity, the lower the mortality risk of the elderly (HR=0.967, 95%CI: 0.956-0.978), while the more negative effectivity, the higher the mortality risk of the elderly (HR=1.024, 95%CI: 1.013-1.035).
CONCLUSION
The negative effectivity of the elderly in all dimensions may increase the mortality risk of elderly people. We ought to dredge the negative emotions of the elderly in time. In the health promotion of the elderly, we should also pay attention to the encouragement of positive effectivity in all dimensions, which requires the joint efforts of families, communities and governments.
Adolescent
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Aged
;
China/epidemiology*
;
Female
;
Humans
;
Longevity
;
Longitudinal Studies
;
Male
;
Proportional Hazards Models
;
Prospective Studies
;
Risk Factors


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