Increased poly(ADP-ribose) polymerase activity in lymphoblastoid cell lines from centenarians

 Poly(ADP-ribosyl)ation is a posttranslational modification of nuclear proteins which is catalyzed by poly(ADP-ribose) polymerase and represents an immediate response of eukaryotic cells to oxidative and other types of DNA damage. Previously a strong correlation had been detected between maximal poly(ADP-ribose) polymerase activity in permeabilized mononuclear leukocytes of various mammalian species and species-specific life span. To study a possible relation between longevity and poly(ADP-ribosyl)ation in humans we measured maximal oligonucleotide-stimulated poly(ADP-ribose) polymerase activity in permeabilized, Epstein-Barr virus transformed lymphoblastoid cell lines from a French population of 49 centenarians and 51 controls aged 20–70 years. Maximal enzyme activity was significantly higher in centenarians than in controls [median of controls: 9035 cpm/10⁶ cells (lower quartile: 6156; upper quartile: 11,410); median of centenarians: 10,380 cpm/10⁶ cells (lower quartile: 7994; upper quartile: 12,991); P=0.031 by Mann-Whitney U test]. In a subset of 16 controls and 24 centenarians, cellular poly(ADP-ribose) polymerase content was determined by quantitative western blotting, thus allowing the calculation of specific enzyme activity. The latter was significantly higher in centenarians (P=0.006), the median value for centenarians being about 1.6-fold that of controls. Specific poly(ADP-ribose) polymerase activity was a more powerful parameter for differentiating between centenarians and controls than enzyme activity relative to cell number. In addition, in a genetic association study we analyzed 437 DNA samples (239 centenarians and 198 controls) by PCR amplification of a polymorphic dinucleotide repeat located in the promoter region of the poly(ADP-ribose) polymerase gene in an attempt to detect an association between this polymorphic marker and variability of enzyme activity or human longevity. However, this genetic analysis revealed no significant enrichment of any of the alleles or genotypes identified among centenarians or controls, but its power was limited by the relatively weak hetero-zygosity of this polymorphic marker in our population (51%). Viewed together with previous results on poly(ADP-ribose) polymerase activity in various mammalian species, the present data provide further evidence for the notion that longevity is associated with a high poly(ADP-ribosyl)ation capacity. Received: 5 September 1997 / Accepted: 10 November 1997     

Discovery of novel non-synonymous SNP variants in 988 candidate genes from 6 centenarians by target capture and next-generation sequencing

Despite evidence of a substantial genetic component, the genetic factors that underlie longevity in humans remain to be identified. Previous genome-wide linkage and association studies have not found strong evidence for the contribution of common variants besides the APOE gene, suggesting the role of rare variants in human longevity. To discover rare variants that might contribute to longevity, we selected 988 candidate genes and performed a pilot study to identify novel non-synonymous variants in 6 Ashkenazi Jewish centenarians older than 105. Our candidate genes act in pathways implicated in aging and longevity, including neurodegeneration, cognitive function, lipid metabolism, DNA repair, and genome maintenance. By implementing custom-designed Agilent SureSelect target capture and next-generation sequencing, we discovered a total of 89 novel non-synonymous SNPs (nsSNPs) and validated 51 nsSNPs by iPLEX MassArray assays. Genotyping analysis of these novel SNPs in 410 Ashkenazi Jewish controls and 390 centenarians showed significant enrichment (5.3 fold, p = 0.02) of the p.Y318C variant in PMS2 and significant depletion (7.5 fold, p = 0.04) of the p.V465A variant in GABRR3 in centenarians compared to controls. Our study presents the potential of targeted next-generation sequencing for discovery of rare but functional genetic variation which may lead to exceptional longevity in humans.     

Cancer in the oldest old

Our previous work revealed that 88% of centenarians delay or escape the age-related lethal diseases cardiac disease, stroke and diabetes. In the cases of those having a history of cancer we have observed anecdotes of centenarians presenting with large primary tumors that would have otherwise been expected to have metastasized and to have been lethal. However, these tumors were removed without consequence. To better understand the relationship between cancer and exceptional longevity, we quantified age of cancer diagnoses, life-time clinically evident cancer prevalence, tobacco use and family histories through medical record review and interviews. One thousand one hundred and forty-three subjects were studied revealing 20% (N=152) of female and 22% (N=80) of male centenarians with a history of non-skin cancer. The most common cancers were prostate (11.7% of males), breast (8.2% of females), and colon (5.7%). The average age of diagnosis was 80.5 years compared to 63.2 years in the general population according to National Cancer Institute SEER data. Similar delays were noted when age of onset was examined according to specific type of cancer. In conclusion, the age of diagnosis of cancer is relatively delayed in those who live to 100 years. Some cancers are very rare among these individuals suggesting that there are certain cancers that may be incompatible with survival to extreme old age.     

Hip fractures in centenarians

The centenarian population is increasing yet there is little about their morbidity and mortality rates following hip fracture. The aim was to review centenarians treated for proximal femoral fractures in Edinburgh describing treatment outcomes in relation to mortality, walking ability and residential status comparing centenarians with a the more typical hip fracture population. In this retrospective review, 18 centenarians sustaining hip fractures in Edinburgh between 1998 and 2002 were compared to 18 randomly selected "normal" hip fracture patients aged 75-83 years. Centenarian in-hospital, 1 and 4 month mortality was 11.1, 33.3 and 50%, respectively, versus 0, 0 and 5.6% in the normal group. Centenarian 4 month mortality was significantly greater than that of the normal group (Fisher's Exact Test, P = 0.00723). A total of 22.2% of centenarians regained pre-fracture walking ability compared to 58.8% of the normal patients. A total 28.6% of centenarians could continue living independently post-fracture compared to 69.2% of the normal group.     

Characteristics of centenarians’ lifestyles and their contribution to life satisfaction: A case study conducted on Hainan Island

BackgroundCentenarians represent an intriguing model for healthy aging. They appear to have adapted well to their lives and are likely to be influenced by previous lifestyle habits, and their life satisfaction is influenced by mental and psychological health.ObjectiveThe aim of this study is to explore centenarians’ lifestyles by sex and their potential contribution to life satisfaction.MethodIn order to examine the common characteristics of centenarians in Hainan and the potential differences between men and women, a cross-sectional survey was conducted with 223 cognitively-intact Chinese centenarians. We also explored the association between life satisfaction and other physical factors using binary logistic regression and principal component analysis.ResultsThe results provided supplementary evidence indicating that women tended to live longer than men. However, the difference in life satisfaction observed between the sexes was not obvious (p = 0.659). The proportion of physical factors between each sex showed a similar trend in distribution. Most centenarians’ lifestyles were similar, in that they followed a light diet and did not smoke or drink alcohol. Centenarians in better physical condition and with higher self-assessment, as well as those with “alcohol and tobacco habits,” were more satisfied with their life. Of the factors examined in the binary logistic regression, sleep satisfaction was the only factor significantly positively correlated with life satisfaction (p < .01).ConclusionThe research findings elucidated physiological and psychological health in centenarians and provided a model of healthy aging strategies for reference purposes.     

海南百岁老人12项肥胖相关指标与全因死亡的关联研究

目的描述和分析BMI、腰围、腰臀比、腰高比、小腿围、腰围小腿围比值(WCR)、脂质蓄积指数(LAP)、内脏脂肪指数(VAI)、中国内脏脂肪指数(CVAI)、身体形态指数、中国身体形态指数(CABSI)和身体圆度指数与海南百岁老人全因死亡间的关联。方法整群抽样方法抽取的海南百岁老人共1 002人。随访时间的M(Q1, Q3)为4.16(1.31, 5.04)年, 结局为全因死亡, 使用Cox比例风险回归分析各肥胖相关身体测量指标与全因死亡的关联, 并使用受试者工作特征曲线曲线下面积(AUC)进行比较。结果总人群中小腿围对全因死亡的判定能力最强, AUC为0.61(95%CI:0.57～0.64), 分性别结果与总人群一致(P<0.05)。WCR次之(AUC为0.58), 再次是BMI、LAP和腰围, AUC分别为0.55、0.55和0.54, 而CABSI、腰臀比和VAI的判定能力较弱, AUC分别为0.51、0.50和0.50。结论本研究比较了12项肥胖相关指标与海南百岁老人全因死亡间的关联, 发现小腿围的预测判定能力最好, 且呈剂量反应关系, 提示可作为长寿老人死亡风险预测的参...     

Argyrophilic grain disease: frequency and neuropathology in centenarians

Argyrophilic grain disease (AGD) is a progressive degenerative disease of the human brain, the prevalence of which increases with advancing age. The features of AGD in autopsied brains from 32 centenarians were studied using phosphorylated tau (AT8) immunostaining combined with Gallyas–Braak staining and 4R tau-specific antibody (RD4) immunostaining. Ten of 32 centenarians were diagnosed as AGD, yielding an overall frequency of 31.3%. In the demented group, nine (39.1%) of 23 cases were found with argyrophilic grains (AGs), while in the non-demented group, AGs were found in only one (11.1%) of nine cases, the difference between them being significant (P<0.05). Among the cases with Alzheimer’s disease (AD), five (41.7%) of 12 were found with AGs. One (25%) of four cases with senile dementia with tangles (SDT) also suffered from AGD. Dementia caused by “pure” AGD accounted for 13% (3/23) among demented subjects. Our findings indicated that there is a high frequency of AGD in centenarians. In agreement with previous studies, we favor the view that age may be one of the risk factors for AGD.     

海南百岁老人营养状况对全因死亡影响的前瞻性队列研究

目的探讨海南百岁老人营养状况与全因死亡风险之间的关系。方法利用中国海南百岁老人队列研究2014-2021年调查数据, 本研究共纳入1 002名基线资料完整的海南百岁老人, 随访其生存与死亡结局。根据简易营养评估量表将百岁老人的营养状况分为营养良好(12～14分)、营养不良风险(8～11分)和营养不良(0～7分)3组。利用Kaplan-Meier曲线评估百岁老人的生存状况;利用Cox比例风险回归模型评估营养状况与全因死亡之间的关联。结果 2021年5月31日随访结束后, 共发现522名百岁老人死亡, 7年全因死亡率为52.10%(522/1 002)。与营养良好组相比, 营养不良导致的平均减寿为0.62年。生存分析显示, 营养不良组全因死亡率高于其他组(χ2=16.45, P<0.001)。多因素Cox比例风险回归分析结果显示, 与营养良好的百岁老人相比, 营养不良组全因死亡风险更高(HR=1.65, 95%CI:1.18～2.31)。亚组分析发现女性百岁老人该关联更为显著。结论营养不良与海南百岁老人高全因死亡风险相关, 提示应及时评估和关注百岁老人特别是女性老人营养状况对其健康长...     

Vascular procedures in nonagenarians and centenarians are safe

Background

An increasing number of elderly patients present for elective and emergent vascular procedures. The purpose of this study was to analyze the 30-day and long-term outcome of patients in their 10th decade of life undergoing vascular procedures.

Methods

We reviewed the outcomes of all patients in the 10th decade of life included in our registry.

Results

In a 15-year period, there were 176 patients, 102 women and 74 men, with a mean age of 92 (range 90–102) undergoing 196 vascular operations for acute and chronic limb ischemia, aortic and popliteal aneurysms, and carotid stenosis. Overall morbidity and mortality rates were comparable as well as the return to preoperative functional status.

Conclusions

Patients in their 90s can safely undergo vascular procedures with reasonable early outcomes. Most patients return to their preoperative status. Age alone should not be a determinant in refusing surgery in this age group.