Objective To examine whether the selectivity of visual cortical neurons to stimulus spatial frequencies would be affected by aging in cats.Methods In vivo extracellular single-unit recording techniques were employed t...Objective To examine whether the selectivity of visual cortical neurons to stimulus spatial frequencies would be affected by aging in cats.Methods In vivo extracellular single-unit recording techniques were employed to record the tuning responses of V1 neurons to different stimulus spatial frequencies in old and young adult cats.Results Statistical analysis showed that the mean optimal spatial frequency of grating stimuli that evoked the maximal response of V1 neurons in old cats was significantly lower than that in young adult cats.Furthermore,the mean high cut-off spatial frequency of grating stimuli that evoked the half amplitude of the maximal response of V1 neurons in old cats was also significantly lower than that in young adult cats.Conclusion These results are consistent with those reported in the V1 of old monkeys,suggesting that the age-related decline in the selectivity of visual cortical cells to spatial frequency could be generalized to all mammalian species and might contribute to visual acuity reduction in senescent individuals.展开更多
BACKGROUND Decreased ovarian reserve function is an ovarian hypofunction disease that occurs in women before 40 years of age,leading to a decline in fertility and perimeno-pausal symptoms,such as irregular menstruatio...BACKGROUND Decreased ovarian reserve function is an ovarian hypofunction disease that occurs in women before 40 years of age,leading to a decline in fertility and perimeno-pausal symptoms,such as irregular menstruation,amenorrhea,infertility,de-creased libido,and autonomic nervous dysfunction.Fenmatong(FMT)is a com-pound mixture of estradiol tablets and estradiol didroxyprogesterone tablets,which can improve ovarian reserve function by supplementation of exogenous estrogen.However,this treatment has also been shown to cause breast pain,gastrointestinal discomfort,irregular vaginal bleeding,and changes in sexual desire.In severe cases,FMT can promote the development of breast cancer,endometrial cancer,and venous embolic disease.AIM To observe the effects of Kuntai capsules and FMT on endocrine indexes and uterine artery blood circulation in patients with decreased ovarian reserve func-tion.METHODS Patients(130)with decreased ovarian reserve function,who were treated in our hospital from May 2018 to May 2020,were divided into two groups:The FMT group,in which patients were treated with FMT,and the observation group,in which patients were treated with Kuntai capsules.Chinese medicine symptom scores,uterine artery blood flow parameters,ovarian ultrasound test indexes,pictorial blood loss assessment chart(PBAC)scores,and hormone levels were recorded,and total effective rates were calculated for both groups.RESULTS The total effective rate in the observation group was higher than that in the FMT group(P<0.05).After treatment,primary symptoms,including low menstrual volume,delayed menstruation,red color and thick consistency of menses,di-zziness,palpitation,weakness at the waist and knee,insomnia and excessive dreaming,irritability,and dryness and astringency of the pudendal canal in the observation group decreased,and scores for primary and secondary symptoms in the observation group were significantly lower than those in the FMT group(P<0.05).The systolic peak flow rate(PSV),end-diastolic flow rate(EDV),ovarian diameter,sinus follicle count,and resistance index(RI)of the uterine arteries in the observation group and FMT group increased after treatment.Notably,the PSV,EDV,ovarian diameter,and antral follicle count in the observation group were higher than those in the FMT group,whereas the RI in the observation group was lower than that in the FMT group(P<0.05).The PBAC scores in the observation and FMT groups increased after treatment,with that in the ob-servation group becoming significantly higher than that in the FMT group(P<0.05).After treatment,estradiol(E2)and anti-Mullerian hormone(AMH)levels increased,whereas follicle-stimulating hormone(FSH)levels decreased in the observation group and FMT group;E2 and AMH levels became significantly higher and FSH levels became significantly lower in the observation group than in the FMT group(P<0.05).CONCLUSION Compared with FMT,Kuntai capsules promoted uterine artery blood circulation,improved menstruation,relieved symptoms,regulated endocrine function,and improved curative effects.展开更多
Objective To evaluate the association between serum uric acid(SUA)and kidney function decline.Methods Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older popu...Objective To evaluate the association between serum uric acid(SUA)and kidney function decline.Methods Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis.The kidney function decline was defined as an annual estimated glomerular filtration rate(e GFR)decrease by>3 mL/min per 1.73 m^(2).Multivariable logistic regression was applied to determine the association between SUA and kidney function decline.The shape of the association was investigated by restricted cubic splines.Results A total of 7,346 participants were included,of which 1,004 individuals(13.67%)developed kidney function decline during the follow-up of 4 years.A significant dose-response relation was recorded between SUA and the kidney function decline(OR 1.14,95%CI 1.03-1.27),as the risk of kidney function decline increased by 14%per 1 mg/d L increase in SUA.In the subgroup analyses,such a relation was only recorded among women(OR 1.22,95%CI 1.03-1.45),those aged<60 years(OR 1.22,95%CI 1.05-1.42),and those without hypertension and without diabetes(OR 1.22,95%CI 1.06-1.41).Although the dose-response relation was not observed in men,the high level of SUA was related to kidney function decline(OR 1.83,95%CI 1.05-3.17).The restricted cubic spline analysis indicated that SUA>5 mg/dL was associated with a significantly higher risk of kidney function decline.Conclusion The SUA level was associated with kidney function decline.An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.展开更多
1.Background When searching for the term“muscle power”on Google Scholar,about 3.7 million hits come up in 60 ms,and for the past 3 years,there were approximately 225 yearly peer-reviewed publications dealing with mu...1.Background When searching for the term“muscle power”on Google Scholar,about 3.7 million hits come up in 60 ms,and for the past 3 years,there were approximately 225 yearly peer-reviewed publications dealing with muscle power.Muscle power has been used to assess and predict athletic performance,to determine muscle rehabilitation following injury or disease,to measure functional decline as occurs in aging,and many other topics.展开更多
Rapid population aging has led to an increased focus on age-related conditions such as sarcopenia.causing loss of muscle mass and strength^([1,2]). Sarcopenia is associated with adverse outcomes,including falls, funct...Rapid population aging has led to an increased focus on age-related conditions such as sarcopenia.causing loss of muscle mass and strength^([1,2]). Sarcopenia is associated with adverse outcomes,including falls, functional decline, frailty, and mortality, which can lower the quality of life and shorten lifespan^([1,2]).展开更多
In 2019,China had over 13.14 million dementia cases,with incidence rates of(56.47–207.08)/100,000[1].Early cognitive impairment—a key dementia symptom—reduces quality of life,increases care dependence,and lowers su...In 2019,China had over 13.14 million dementia cases,with incidence rates of(56.47–207.08)/100,000[1].Early cognitive impairment—a key dementia symptom—reduces quality of life,increases care dependence,and lowers survival in older adults[2].A decline in physical function can also be observed in older adults with increasing age.Grip strength has been shown to be a marker of overall physiological function in older adults.展开更多
BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,wit...BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,with renal function at the time of diagnosis and prognosis being strongly correlated.Mycophenolate mofetil(MMF)is a drug with a good immunomodulatory effect and is commonly used clinically.However,its effects in IgAN have not yet been clearly demonstrated.Therefore,herein,we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment.METHODS Between January 2011 and December 2020,200 patients with moderate-to-severe IgAN were included in this study,all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University.All patients underwent a renal puncture biopsy,which revealed primary IgAN with a glomerular filtration rate(GFR)of 30–60 mL/min.The patients were divided into a glucocorticoid therapy group(GTG)and an immunosuppressive therapy group(ITG)according to the different treatment regimens,with 100 patients in each group.Based on general treatments,such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,patients in the GTG were administered prednisone 0.5–0.8 mg/(kg·d^(-1))for 4–8 wk,which was reduced by 5 mg every two weeks until the maintenance(30 mg/d)dose was reached and maintained for 12 mo.In the ITG,MMF was administered at 1.0 g/d for 6–12 mo,followed by a maintenance dosage of 0.5 g/d for 12 mo.Age,sex,blood pressure,24-h urinary egg white measurement,serum creatinine(Scr),blood uric acid,blood albumin,blood potassium(K),hemoglobin,GFR,alanine aminotransferase,total cholesterol(T-CHO),fasting blood glucose,and body mass index were recorded.The 24-h urinary protein,Scr,and GFR levels were recorded 3,6,9,and 12 mo after treatment.Follow-up data were also collected.RESULTS No discernible differences existed between the two groups in terms of age,sex,blood pressure,creatinine,24-h urinary protein level,GFR,or other biochemical indicators at the time of enrollment.Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function.Nine months after treatment,the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG.By the 12th month of treatment,the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month.In addition,the overall response rate in the ITG was significantly higher than that in the GTG.The occurrence of side effects did not vary significantly between the two regimens;however,endpoint events were significantly more common in the GTG than in the ITG.The follow-up time for the GTG was noticeably lower than that for the ITG.CONCLUSION Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.展开更多
In the context of rapid societal ageing,the analysis and address of ageing have become increasingly imperative.Ageing is characterized by the accumulation of molecular,cellular,and organ damage,leading to systemic fun...In the context of rapid societal ageing,the analysis and address of ageing have become increasingly imperative.Ageing is characterized by the accumulation of molecular,cellular,and organ damage,leading to systemic functional decline and increased disease susceptibility.展开更多
Dear Editor,Cellular senescence is characterized by growth arrest and the onset of a senescence-associated secretory phenotype (SASP)(Consortium et al., 2023;Liu et al., 2023;Zhang et al., 2023). Consequently, senesce...Dear Editor,Cellular senescence is characterized by growth arrest and the onset of a senescence-associated secretory phenotype (SASP)(Consortium et al., 2023;Liu et al., 2023;Zhang et al., 2023). Consequently, senescent cells that accumulate within aged organs have the capacity to disseminate pro-senescence and pro-inflammatory signals, promoting structural tissue deterioration and functional decline, culminating in organismal aging (Cai et al., 2022;Consortium et al., 2024).展开更多
Aging is characterized by progressive functional decline driven by stem cell exhaustion,chronic inflammation,and cellular senescence.Mesenchymal progenitor cells(MPCs),which play a central role in tissue repair,are pa...Aging is characterized by progressive functional decline driven by stem cell exhaustion,chronic inflammation,and cellular senescence.Mesenchymal progenitor cells(MPCs),which play a central role in tissue repair,are particularly vulnerable to age-associated dysfunction.Lei et al.(Cell 188:1-22,2025)address this limitation by engineering human embryonic stem cell-derived MPCs with enhanced FOXO3 activity(termed SRCs).Intravenous administration of FOXO3-SRCs to aged cynomolgus macaques significantly slowed aging across multiple organs compared to wild-type MPCs.SRC treatment improved cognitive performance,preserved brain structure,protected bone integrity,and rejuvenated immune function.Transcriptomic and DNA methylation aging clocks revealed substantial reductions in biological age,with the most pronounced rejuvenation observed in the reproductive system,skin,lung,muscle,and hippocampus.These effects were partly attributed to SRC-derived exosomes enriched in gero-protective proteins and metabolites.Importantly,SRCs exhibited robust safety,showing no tumorigenicity or immunogenicity.This work positions FOXO3-enhanced MPCs and their exosomes as promising candidates for systemic anti-aging interventions,shifting the therapeutic paradigm from treating individual diseases to targeting the aging process itself.展开更多
Patients with immunoglobulin A nephropathy(IgAN)can present with diverse clinical manifestations from asympto-matic microscopic hematuria or proteinuria to rapid decline of renal function(Stamellou et al.2023).Many pa...Patients with immunoglobulin A nephropathy(IgAN)can present with diverse clinical manifestations from asympto-matic microscopic hematuria or proteinuria to rapid decline of renal function(Stamellou et al.2023).Many patients with IgAN progress to kidney failure within a span of 10-15 years and nearly all of the patients are at risk of progression to kidney failure over the course of their expected lifetimes(Pitcher et al.2023).However,early identification of IgAN patients at high risk of progression and those who would benefit from early and targeted intervention is a key chal-lenge in the clinical management of IgAN patients.展开更多
基金supported by Natural Science Foundation of Anhui Province(No. 070413138)the Key Research Foundation of Education Department of Anhui Province,China(No. KJ2009A167)
文摘Objective To examine whether the selectivity of visual cortical neurons to stimulus spatial frequencies would be affected by aging in cats.Methods In vivo extracellular single-unit recording techniques were employed to record the tuning responses of V1 neurons to different stimulus spatial frequencies in old and young adult cats.Results Statistical analysis showed that the mean optimal spatial frequency of grating stimuli that evoked the maximal response of V1 neurons in old cats was significantly lower than that in young adult cats.Furthermore,the mean high cut-off spatial frequency of grating stimuli that evoked the half amplitude of the maximal response of V1 neurons in old cats was also significantly lower than that in young adult cats.Conclusion These results are consistent with those reported in the V1 of old monkeys,suggesting that the age-related decline in the selectivity of visual cortical cells to spatial frequency could be generalized to all mammalian species and might contribute to visual acuity reduction in senescent individuals.
文摘BACKGROUND Decreased ovarian reserve function is an ovarian hypofunction disease that occurs in women before 40 years of age,leading to a decline in fertility and perimeno-pausal symptoms,such as irregular menstruation,amenorrhea,infertility,de-creased libido,and autonomic nervous dysfunction.Fenmatong(FMT)is a com-pound mixture of estradiol tablets and estradiol didroxyprogesterone tablets,which can improve ovarian reserve function by supplementation of exogenous estrogen.However,this treatment has also been shown to cause breast pain,gastrointestinal discomfort,irregular vaginal bleeding,and changes in sexual desire.In severe cases,FMT can promote the development of breast cancer,endometrial cancer,and venous embolic disease.AIM To observe the effects of Kuntai capsules and FMT on endocrine indexes and uterine artery blood circulation in patients with decreased ovarian reserve func-tion.METHODS Patients(130)with decreased ovarian reserve function,who were treated in our hospital from May 2018 to May 2020,were divided into two groups:The FMT group,in which patients were treated with FMT,and the observation group,in which patients were treated with Kuntai capsules.Chinese medicine symptom scores,uterine artery blood flow parameters,ovarian ultrasound test indexes,pictorial blood loss assessment chart(PBAC)scores,and hormone levels were recorded,and total effective rates were calculated for both groups.RESULTS The total effective rate in the observation group was higher than that in the FMT group(P<0.05).After treatment,primary symptoms,including low menstrual volume,delayed menstruation,red color and thick consistency of menses,di-zziness,palpitation,weakness at the waist and knee,insomnia and excessive dreaming,irritability,and dryness and astringency of the pudendal canal in the observation group decreased,and scores for primary and secondary symptoms in the observation group were significantly lower than those in the FMT group(P<0.05).The systolic peak flow rate(PSV),end-diastolic flow rate(EDV),ovarian diameter,sinus follicle count,and resistance index(RI)of the uterine arteries in the observation group and FMT group increased after treatment.Notably,the PSV,EDV,ovarian diameter,and antral follicle count in the observation group were higher than those in the FMT group,whereas the RI in the observation group was lower than that in the FMT group(P<0.05).The PBAC scores in the observation and FMT groups increased after treatment,with that in the ob-servation group becoming significantly higher than that in the FMT group(P<0.05).After treatment,estradiol(E2)and anti-Mullerian hormone(AMH)levels increased,whereas follicle-stimulating hormone(FSH)levels decreased in the observation group and FMT group;E2 and AMH levels became significantly higher and FSH levels became significantly lower in the observation group than in the FMT group(P<0.05).CONCLUSION Compared with FMT,Kuntai capsules promoted uterine artery blood circulation,improved menstruation,relieved symptoms,regulated endocrine function,and improved curative effects.
文摘Objective To evaluate the association between serum uric acid(SUA)and kidney function decline.Methods Data was obtained from the China Health and Retirement Longitudinal Study on the Chinese middle-aged and older population for analysis.The kidney function decline was defined as an annual estimated glomerular filtration rate(e GFR)decrease by>3 mL/min per 1.73 m^(2).Multivariable logistic regression was applied to determine the association between SUA and kidney function decline.The shape of the association was investigated by restricted cubic splines.Results A total of 7,346 participants were included,of which 1,004 individuals(13.67%)developed kidney function decline during the follow-up of 4 years.A significant dose-response relation was recorded between SUA and the kidney function decline(OR 1.14,95%CI 1.03-1.27),as the risk of kidney function decline increased by 14%per 1 mg/d L increase in SUA.In the subgroup analyses,such a relation was only recorded among women(OR 1.22,95%CI 1.03-1.45),those aged<60 years(OR 1.22,95%CI 1.05-1.42),and those without hypertension and without diabetes(OR 1.22,95%CI 1.06-1.41).Although the dose-response relation was not observed in men,the high level of SUA was related to kidney function decline(OR 1.83,95%CI 1.05-3.17).The restricted cubic spline analysis indicated that SUA>5 mg/dL was associated with a significantly higher risk of kidney function decline.Conclusion The SUA level was associated with kidney function decline.An elevation of SUA should therefore be addressed to prevent possible kidney impairment and dysfunction.
文摘1.Background When searching for the term“muscle power”on Google Scholar,about 3.7 million hits come up in 60 ms,and for the past 3 years,there were approximately 225 yearly peer-reviewed publications dealing with muscle power.Muscle power has been used to assess and predict athletic performance,to determine muscle rehabilitation following injury or disease,to measure functional decline as occurs in aging,and many other topics.
基金supported by the Ministry of Education Chunhui Program Collaborative Scientific Research Projects(Grant No.:HZKY20220286)Henan Province Foreign Experts Introduction Program(Grant No.:HNGD2022021)+1 种基金Natural Science Foundation of Henan Province(Grant No.:23230042151)the Foundation of the National Key Program of Research and Development of China(Grant No.:2016YFC0900803)。
文摘Rapid population aging has led to an increased focus on age-related conditions such as sarcopenia.causing loss of muscle mass and strength^([1,2]). Sarcopenia is associated with adverse outcomes,including falls, functional decline, frailty, and mortality, which can lower the quality of life and shorten lifespan^([1,2]).
基金supported by the Shanghai New Three-year Action Plan for Public Health(Grant No.GWV-10.1-XK16)the US National Institute on Aging(RO1-AGO34479).
文摘In 2019,China had over 13.14 million dementia cases,with incidence rates of(56.47–207.08)/100,000[1].Early cognitive impairment—a key dementia symptom—reduces quality of life,increases care dependence,and lowers survival in older adults[2].A decline in physical function can also be observed in older adults with increasing age.Grip strength has been shown to be a marker of overall physiological function in older adults.
基金This study was approved by the Ethics Committee of Wuxi People's Hospital affiliated with Nanjing Medical University(approval no.KY23117).
文摘BACKGROUND Immunoglobulin A nephropathy(IgAN)is a common form of chronic glomer-ulonephritis.Currently,IgAN is one of the main causes of chronic renal failure in China;its prognosis varies greatly between patients,with renal function at the time of diagnosis and prognosis being strongly correlated.Mycophenolate mofetil(MMF)is a drug with a good immunomodulatory effect and is commonly used clinically.However,its effects in IgAN have not yet been clearly demonstrated.Therefore,herein,we retrospectively compared the effectiveness and safety of prednisone alone or combined with MMF for the treatment of primary IgAN with moderate-to-severe renal impairment.METHODS Between January 2011 and December 2020,200 patients with moderate-to-severe IgAN were included in this study,all of whom were admitted to Wuxi People's Hospital affiliated with Nanjing Medical University.All patients underwent a renal puncture biopsy,which revealed primary IgAN with a glomerular filtration rate(GFR)of 30–60 mL/min.The patients were divided into a glucocorticoid therapy group(GTG)and an immunosuppressive therapy group(ITG)according to the different treatment regimens,with 100 patients in each group.Based on general treatments,such as angiotensin-converting enzyme inhibitors/angiotensin receptor blockers,patients in the GTG were administered prednisone 0.5–0.8 mg/(kg·d^(-1))for 4–8 wk,which was reduced by 5 mg every two weeks until the maintenance(30 mg/d)dose was reached and maintained for 12 mo.In the ITG,MMF was administered at 1.0 g/d for 6–12 mo,followed by a maintenance dosage of 0.5 g/d for 12 mo.Age,sex,blood pressure,24-h urinary egg white measurement,serum creatinine(Scr),blood uric acid,blood albumin,blood potassium(K),hemoglobin,GFR,alanine aminotransferase,total cholesterol(T-CHO),fasting blood glucose,and body mass index were recorded.The 24-h urinary protein,Scr,and GFR levels were recorded 3,6,9,and 12 mo after treatment.Follow-up data were also collected.RESULTS No discernible differences existed between the two groups in terms of age,sex,blood pressure,creatinine,24-h urinary protein level,GFR,or other biochemical indicators at the time of enrollment.Both regimens significantly reduced the 24-h urinary protein quantitation and stabilized renal function.Nine months after treatment,the 24-h urinary protein and Scr of the ITG decreased more significantly than those of the GTG.By the 12th month of treatment,the 24-h urinary protein and Scr in both groups continued to decrease compared to those by the 9th month.In addition,the overall response rate in the ITG was significantly higher than that in the GTG.The occurrence of side effects did not vary significantly between the two regimens;however,endpoint events were significantly more common in the GTG than in the ITG.The follow-up time for the GTG was noticeably lower than that for the ITG.CONCLUSION Prednisone combined with MMF was effective for the treatment of IgAN with moderate-to-severe renal dysfunction.
基金supported by the National Key Research and Development Program of China(2023YFC3605400)the Commission of Chongqing Municipality(2024GGXM003)。
文摘In the context of rapid societal ageing,the analysis and address of ageing have become increasingly imperative.Ageing is characterized by the accumulation of molecular,cellular,and organ damage,leading to systemic functional decline and increased disease susceptibility.
基金supported by the National Natural Science Foundation of China (82125011, 81921006, 92149301, 82322025, 82122024)the National Key Research and Development Program of China(2020YFA0804000, 2022YFA1103700, 2020YFA0112200, 2021YFF1201000, the STI2030-Major Projects-2021ZD0202400)+9 种基金the National Natural Science Foundation of China (92168201, 82330044, 32341001, 92049304, 92049116, 32121001, 82192863, 82071588, 82361148130, 82361148131, 82271600)CAS Project for Young Scientists in Basic Research (YSBR-076, YSBR-012)the Program of the Beijing Natural Science Foundation (Z230011)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2022SDC-XK14)New Cornerstone Science Foundation through the XPLORER PRIZE (2021-1045)Youth Innovation Promotion Association of CAS (E1CAZW0401, 2022083)Excellent Young Talents Program of Capital Medical University (12300927)The Project for Technology Development of Beijing-affiliated Medical Research Institutes (11000023T000002036310)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105)Young Elite Scientists Sponsorship Program by CAST (2021QNRC001)。
文摘Dear Editor,Cellular senescence is characterized by growth arrest and the onset of a senescence-associated secretory phenotype (SASP)(Consortium et al., 2023;Liu et al., 2023;Zhang et al., 2023). Consequently, senescent cells that accumulate within aged organs have the capacity to disseminate pro-senescence and pro-inflammatory signals, promoting structural tissue deterioration and functional decline, culminating in organismal aging (Cai et al., 2022;Consortium et al., 2024).
基金supported by King Abdullah University of Science and Technology(KAUST)Office of Sponsored Research(OSR),under award number BAS/1/1080-01by KAUST Center of Excellence for Smart Health(KCSH),under award number 5932(ML)supported by the KAUST Center of Excellence for Smart Health(KCSH).
文摘Aging is characterized by progressive functional decline driven by stem cell exhaustion,chronic inflammation,and cellular senescence.Mesenchymal progenitor cells(MPCs),which play a central role in tissue repair,are particularly vulnerable to age-associated dysfunction.Lei et al.(Cell 188:1-22,2025)address this limitation by engineering human embryonic stem cell-derived MPCs with enhanced FOXO3 activity(termed SRCs).Intravenous administration of FOXO3-SRCs to aged cynomolgus macaques significantly slowed aging across multiple organs compared to wild-type MPCs.SRC treatment improved cognitive performance,preserved brain structure,protected bone integrity,and rejuvenated immune function.Transcriptomic and DNA methylation aging clocks revealed substantial reductions in biological age,with the most pronounced rejuvenation observed in the reproductive system,skin,lung,muscle,and hippocampus.These effects were partly attributed to SRC-derived exosomes enriched in gero-protective proteins and metabolites.Importantly,SRCs exhibited robust safety,showing no tumorigenicity or immunogenicity.This work positions FOXO3-enhanced MPCs and their exosomes as promising candidates for systemic anti-aging interventions,shifting the therapeutic paradigm from treating individual diseases to targeting the aging process itself.
基金supported,in part,by funding from NIH/NIDDK through the George M.O’Brien Michigan Kidney Translational Core Center,grant:U54 DK137314supported by a grant from the University of Michigan Health System and Peking University Health Sciences Center Joint Institute for Translational and Clinical Research.
文摘Patients with immunoglobulin A nephropathy(IgAN)can present with diverse clinical manifestations from asympto-matic microscopic hematuria or proteinuria to rapid decline of renal function(Stamellou et al.2023).Many patients with IgAN progress to kidney failure within a span of 10-15 years and nearly all of the patients are at risk of progression to kidney failure over the course of their expected lifetimes(Pitcher et al.2023).However,early identification of IgAN patients at high risk of progression and those who would benefit from early and targeted intervention is a key chal-lenge in the clinical management of IgAN patients.
