First-in-human liver transplantation from a centenarian deceased donor after brain death.

Liver transplantation from elderly donors is expanding due to demand for liver grafts, aging of recipients and donors, and introduction of machine perfusion. We report on a liver transplant from a 100-year-old deceased donor after brain death. The liver was transplanted after the use of hypothermic machine perfusion to a 60-year-old recipient with advanced hepatocellular carcinoma undergoing neoadjuvant immunotherapy. Nine months after the transplant, the patient is alive with a functioning graft and no evidence of acute rejection or tumor recurrence.

Hip Fractures in Centenarians: Functional Outcomes, Mortality, and Risk Factors from a Multicenter Cohort Study.

Background: Increasing longevity has caused the very old population to become the fastest-growing segment. The number of centenarians (over 100 years old) is increasing rapidly. Fractures in the elderly lead to excessive medical costs and decreased quality of life with socioeconomic burdens. However, little research has thoroughly examined the functional outcomes and mortality of hip fractures in centenarians. Methods: This is a retrospective observational study. Sixty-eight centenarian hip fracture patients were admitted to the 10 institutions from February 2004 to December 2019. Fifty-six patients with 1-year follow-up were finally included. The following data were obtained: sex, age, body mass index, Charlson comorbidity index value on the operation day, Koval's classification for ambulatory ability, type of fracture, the time interval from trauma to surgery, American Society of Anesthesiologists grade, surgery-related complications, and duration of hospital stay. Postoperative Koval's classification (at 1 year after surgery) and information about death were also collected. Multivariate analysis was performed to analyze the risk factors affecting mortality 1 year after surgery. Results: Mortality rates were 26.8% at 6 months and 39.3% at 1 year. The 90-day mortality was 19.6%, and one of them (2.1%) died in the hospital. The 1-year mortality rates for the community ambulatory and non-community ambulatory groups were 29% and 52%, respectively. Only 9 (16.1%) were able to walk outdoors 1 year after surgery. The remaining 47 patients (83.9%) had to stay indoors after surgery. Multivariate analysis demonstrated that the pre-injury ambulatory level (adjusted hazard ratio, 2.884; p = 0.034) was associated with the risk of mortality. Conclusions: We report a 1-year mortality rate of 39.3% in centenarian patients with hip fractures. The risk factor for mortality was the pre-injury ambulatory status. This could be an important consideration in the planning of treatment for centenarian hip fracture patients.

Hair Zinc and Chromium Levels Were Associated with a Reduced Likelihood of Age Related Cognitive Decline in Centenarians and Oldest-Old Adults.

BACKGROUND: Cognitive function has inevitable decline with advancing age in nature, and age-related cognitive decline (ARCD) is of increasing concern to aging population. Scarce study has involved the associations between hair trace elements and ARCD in older adults, especially in centenarians and oldest-old adults. This study was to investigate the associations between hair trace elements and ARCD in centenarians and oldest-old adults. METHODS: Based on the household registration information of centenarians and oldest-old adults provided by the Civil Affairs Department of Hainan Province, China, the investigators conducted a one-to-one household survey among centenarians (≥100 years old) and oldest-old adults (80-99 years old). All 50 centenarians had a median age of 103 years and females accounted for 68.0%. All 73 oldest-old adults aged 80-99 years had a median age of 90 years and females accounted for 82.2%. Basic information were obtained with questionnaire interview, physical examination, biological test and hair collection by pre-trained local doctors and nurses. An inductively coupled plasma mass spectrometer was used to measure hair trace elements. All data in this study comes from China. Age, sex, body mass index, systolic blood pressure, diastolic blood pressure, smoking, drinking, hemoglobin, albumin, fasting blood pressure, zinc, chromium, copper, selenium, iron, manganese, strontium, lead, magnesium, potassium, and barium were simultaneously included in multivariate Logistic regression analysis. One adjusted model was done with all hair trace elements together. RESULTS: Zinc and chromium levels were significantly lower in participants with ARCD than those without ARCD (P < 0.05 for all). Multivariate Logistic regression analysis indicated that zinc [odds ratio (OR): 0.988, 95%confidence interval (95%CI): 0.977-0.999] and chromium (OR: 0.051, 95%CI: 0.004-0.705) were associated with a reduced likelihood of ARCD (P < 0.05 for all). CONCLUSIONS: Hair zinc and chromium levels were associated with a reduced likelihood of ARCD in centenarians and oldest-old adults. Further studies are necessary to verify if zinc and chromium supplementation has the potential to improve cognitive function and prevent ARCD development.

[Association analysis between sex hormone levels and all-cause mortality in Hainan female centenarians].

Objective: To investigate the distribution characteristics of sex hormones and their relationship with all-cause mortality in Hainan female centenarians. Methods: All the subjects were from China Hainan Centenarian Cohort Study. A total of 717 female centenarians were included in the final analysis. Kaplan-Meier method was used to draw the survival curve, and Cox proportional hazard regression was used to analyze the relationship between sex hormones and survival time. Results: The M(Q1, Q3) of estradiol and progesterone among female centenarians was 32.60 (18.40, 58.70) pmol/L and 0.62 (0.32, 1.01) nmol/L. The estradiol (pmol/L) and progesterone (nmol/L) in the survival and death groups were 26.65 vs.37.80, 0.54 vs.0.69, respectively, with statistical differences (P<0.05). Cox multivariate analysis showed that estradiol and progesterone were significantly associated with death (P<0.05), the hazard ratio (HR) of estradiol Q4 was 1.58 (95%CI: 1.17-2.15), and the HR of progesterone Q3 was 1.53 (95%CI: 1.10-2.12), HR for Q4 was 1.63 (95%CI: 1.15-2.32). Subgroup and cross-analysis showed that estradiol was statistically significant with hypertension, diabetes, and low high-density lipoprotein cholesterol (P<0.05), and progesterone interacted with diabetes (P=0.016), while testosterone interacted with low high-density lipoprotein cholesterol (P=0.034). Conclusion: It is suggested that the estrogen levels of female centenarians in Hainan were associated with a higher mortality risk and an increased risk of cardiovascular metabolic disease (such as diabetes, hypertension, and abnormal lipid metabolism).

Centenarians: who are they? A description of the total Swedish centenarian population in terms of living arrangements, health, and care utilization.

BACKGROUND: The global centenarian population has doubled each decade and is expected to continue growing. However, information regarding how they live, their health status, and care needs is limited. AIMS: This study aims to describe the total Swedish centenarian population in terms of health status, living arrangements, and socio-demographic characteristics. METHODS: This nationwide register-based study included all Swedish people reaching age 100 between 2013 and 2018. We analyzed their socio-demographic characteristics, living arrangements, number of prescribed drugs, and health status. Moreover, their care transitions from age 100 and two years forward were described. RESULTS: Of 5,882 centenarians (80.7% women), only 15.0% lived at home without formal care and 24.5% cohabited on their 100th birthday. Men (22.7%) were more likely than women (13.2%) to live at home without care. Approximately half of the centenarians lived in care homes, with fewer men (41.0%) than women (54.0%). Around 66.6% had a child living within the 50 km range. Most (76.5%) had an income below the median for Swedish older adults. Almost none were free from drugs, and polypharmacy was common (65.3%). Over half had at least one morbidity. Two years later, only 4.3% lived at home without care, and 63.9% died. CONCLUSION: Sweden's centenarian population is highly dependent on home care and care homes. Among the ones still living at home, the vast majority live alone and have low incomes. Strategies to manage health and social care demands of this growing population group in the coming decade are important.

Anti-Melanogenic and Antioxidant Activity of Bifidobacterium longum Strain ZJ1 Extracts, Isolated from a Chinese Centenarian.

Melanin produced by melanocytes protects our skin against ultraviolet (UV) radiation-induced cell damage and oxidative stress. Melanin overproduction by hyperactivated melanocytes is the direct cause of skin hyperpigmentary disorders, such as freckles and melasma. Exploring natural whitening agents without the concern of toxicity has been highly desired. In this study, we focused on a Bifidobacterium longum strain, ZJ1, isolated from a Chinese centenarian, and we evaluated the anti-melanogenic activity of the distinctive extracts of ZJ1. Our results demonstrated that whole lysate (WL) and bacterial lysate (BL) of ZJ1 ferments efficiently reduce α-melanocyte-stimulating hormone (α-MSH)-induced melanin production in B16-F10 cells as well as the melanin content in zebrafish embryos. BL and WL downregulate melanogenesis-related gene expression and indirectly inhibit intracellular tyrosinase activity. Furthermore, they both showed antioxidant activity in a menadione-induced zebrafish embryo model. Our results suggest that ZJ1 fermentation lysates have application potential as therapeutic reagents for hyperpigmentary disorders and whitening agents for cosmetics.

Targeted sequencing of the 9p21.3 region reveals association with reduced disease risks in Ashkenazi Jewish centenarians.

Genome-wide association studies (GWAS) have pinpointed the chromosomal locus 9p21.3 as a genetic hotspot for various age-related disorders. Common genetic variants in this locus are linked to multiple traits, including coronary artery diseases, cancers, and diabetes. Centenarians are known for their reduced risk and delayed onset of these conditions. To investigate whether this evasion of disease risks involves diminished genetic risks in the 9p21.3 locus, we sequenced this region in an Ashkenazi Jewish centenarian cohort (centenarians: n = 450, healthy controls: n = 500). Risk alleles associated with cancers, glaucoma, CAD, and T2D showed a significant depletion in centenarians. Furthermore, the risk and non-risk genotypes are linked to two distinct low-frequency variant profiles, enriched in controls and centenarians, respectively. Our findings provide evidence that the extreme longevity cohort is associated with collectively lower risks of multiple age-related diseases in the 9p21.3 locus.

Incidence and risk factors of admission deep venous thrombosis in nonagenarians and centenarians with intertrochanteric fracture: a retrospective study.

PURPOSE: The objective of this study was to identify the risk factors for admission deep venous thrombosis (aDVT) and proximal aDVT in nonagenarians and centenarians with intertrochanteric fracture (IF). METHODS: We collected statistics on nonagenarians and centenarians with IF admitting from January 2010 to October 2022. Patients with aDVT were considered as the aDVT group and those without aDVT as the non-aDVT group. Additionally, we also conducted a subgroup analysis based on the location of aDVT to investigate the predictors of proximal aDVT. The demographics, comorbidities and admission laboratory examinations of patients were computed by univariate analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis. RESULTS: In our study, the rate of aDVT (109 of 318) was 34.3%, and 5.7% (18 of 318) of patients had proximal aDVT. Logistic regression analysis showed that female patients and a high level of D-dimer were risk factors for aDVT. Similarly, hypoproteinemia and a high level of D-dimer were found to be risk factors for proximal aDVT. ROC curve analysis indicated the cut-off values of D-dimer to predict the aDVT and proximal aDVT were 1.28 mg/L and 1.485 mg/L, respectively. CONCLUSIONS: Our findings investigated the risk factors of aDVT and proximal aDVT in nonagenarians and centenarians with IF and identified the cut-off values of D-dimer, helping us assess the risk of aDVT and proximal aDVT to manage early targeted interventions.

[Distribution characteristics of body mass index among Chinese oldest-old aged 80 years and above].

Objective: To investigate body mass index (BMI) level, identify the main type of nutritional problem, and describe the population distribution characteristics of BMI among Chinese people aged 80 years or above. Methods: The data of 9 481 oldest-old individuals were obtained from the 2017-2018 Chinese Longitudinal Healthy Longevity Survey. The Lambda-Mu-Sigma method, weighted estimates of BMI, and comparisons by BMI quintiles were used to describe the BMI level and distribution characteristics among the oldest-old. Results: The average age of the participants was (91.9±7.7) years, with P50 of the weighted BMI at 21.9 (95%CI: 21.8-22.0) kg/m2. The result of BMI level showed a decreasing trend with age, with a rapid decline before age 100, and then the trend became slower. There are about 30% of the oldest-old classified as undernutrition, but the prevalence of overnutrition is only about 10%. The population distribution characteristics by BMI quintiles showed the oldest-old with lower BMI levels were likely to have the following characteristics: sociodemographically, to be older, female, ethnic minority, unmarried/divorced/widowed, rural residents, illiterate, with inadequate living expenses, located in Central, South, or Southwest China; regarding lifestyles, lower BMI levels were observed for participants who were smoking, not exercising, lack of leisure activities, or with poor dietary diversity; considering functional status, participants with lower BMI levels were those who have poor chewing ability, disability in activities of daily living, cognitive impairment, hearing loss, visual impairment, or poor self-rated health status. The oldest-old with higher BMI levels were likely to have heart disease, hypertension, cerebrovascular disease, and diabetes. Conclusions: The overall BMI level was low among the Chinese oldest-old and it showed a downward trend with age. Currently, the main nutritional problem among the Chinese oldest-old was undernutrition rather than overweight or obesity. Management of healthy lifestyles, functional status, and diseases would be helpful to reduce the risk of undernutrition among the oldest-old.

Clinical and Demographic Characteristics of Centenarians versus Other Age Groups Over 75 Years with Hip Fractures.

Objective: The primary objective was to describe the clinical characteristics, management, and outcomes of centenarians with fragility hip fracture and compare them to other age groups. The secondary objective was to determine the variables associated with length of stay, in-hospital mortality and 30-day mortality. Materials and Methods: This is a secondary analysis of the Spanish National Hip Fracture Registry. We included patients ≥75 years admitted for fragility hip fractures in 86 Spanish hospitals between 2017 and 2019, dividing the sample into four age groups. The variables studied were baseline characteristics, type of fracture, management, length of stay, in-hospital mortality and 30-day mortality. Results: We included 25,938 patients (2888 were 75-79 years old; 14,762 octogenarians; 8,035 nonagenarians and 253 centenarians). Of the centenarians, 83% were women, 33% had severe dementia, 9% had severe dependency and 36% lived in residential care homes. Six out of ten had intertrochanteric fracture. Length of hospital stay was 8.6 days; in-hospital mortality was 10.3% and 30-day mortality 20.9%. Older age groups had more women, severe functional dependency, severe dementia, intertrochanteric fracture, living in care facilities and being discharged to nursing care. They had less frequent early mobilization, osteoporosis treatment and discharge to rehabilitation units. In-hospital and 30-day mortality were higher with increasing age. In centenarians, time to surgery >48 hours was independently associated with length of stay (correlation coefficient 3.99 [95% CI: 2.35-5.64; p<0.001]) and anaesthetic risk, based on an ASA score of V, was related to 30-day mortality (ASA score II [OR 0.25, 95% CI: 0.09-0.70; p=0.009] and ASA score III [OR 0.43, 95% CI: 0.19-0.96; p=0.039]). Conclusion: Centenarians had different clinical characteristics, management and outcomes. Although centenarians had worse outcomes, nearly 4 out of 5 centenarians were alive one month after surgery.

The Independent Impact of Peripheral Arterial Disease on Mortality in Nonagenarians and Centenarians Who Were Treated in an Intensive Care Unit: A Consecutive Cohort of 1 108 Patients.

OBJECTIVE: To investigate the clinical characteristics, risk factors, and outcomes of inpatients with peripheral arterial disease (PAD) including lower extremity PAD, abdominal aortic aneurysm (AAA), and carotid artery disease in a large cohort of critically ill patients aged ≥ 90 years. METHODS: A retrospective analysis was conducted of all adult patients aged ≥ 90 years consecutively admitted to the intensive care unit at a tertiary care centre in Hamburg, Germany, between 1 January 2008 and 30 April 2019. Multivariable regression and Kaplan-Meier methods were used to determine the independent impact of PAD on short and long term mortality endpoints. The analyses were adjusted for confounding by several sociodemographic and clinical parameters including Charlson Comorbidity Index (CCI) and established clinical risk scores. RESULTS: A total of 1 108 eligible patients were identified (92.3 years, 33% men). Of these, 24% had PAD (9% lower extremity PAD, 2% AAA, 15% coronary artery disease) and 76% did not have any history of PAD and were used as a comparison group. When compared with the comparison group, patients with PAD had a higher CCI (2 vs. 1, p < .001), more often had chronic kidney disease (28% vs. 21%, p = .019), and renal replacement therapy (5% vs. 2%, p = .016). Furthermore, they needed vasopressors (48% vs. 40%, p = .027) and parenteral nutrition (10% vs. 6%, p = .041) more often. After adjusting for confounding, PAD was independently associated with increased in hospital (hazard ratio [HR] 1.97, 95% confidence interval [CI] 1.39 - 2.81, p < .001) and long term mortality rates (HR 1.32, 95% CI 1.05 - 1.66, p = .019). CONCLUSION: One of four critically ill nonagenarians and centenarians in an ICU in Germany had PAD. PAD was associated with both higher short and long term mortality rates while its impact outweighed higher age. Future studies should address this increasingly important population beyond 89 years of age.

Human centenarian-associated SIRT6 mutants modulate hepatocyte metabolism and collagen deposition in multilineage hepatic 3D spheroids.

Non-alcoholic fatty liver disease (NAFLD), encompassing fatty liver and its progression into nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC), is one of the rapidly rising health concerns worldwide. SIRT6 is an essential nuclear sirtuin that regulates numerous pathological processes including insulin resistance and inflammation, and recently it has been implicated in the amelioration of NAFLD progression. SIRT6 overexpression protects from formation of fibrotic lesions. However, the underlying molecular mechanisms are not fully delineated. Moreover, new allelic variants of SIRT6 (N308K/A313S) were recently associated with the longevity in Ashkenazi Jews by improving genome maintenance and DNA repair, suppressing transposons and killing cancer cells. Whether these new SIRT6 variants play different or enhanced roles in liver diseases is currently unknown. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect liver metabolism and associated diseases. We present evidence that overexpression of centenarian-associated SIRT6 variants dramatically altered the metabolomic and secretomic profiles of unchallenged immortalized human hepatocytes (IHH). Most amino acids were increased in the SIRT6 N308K/A313S overexpressing IHH when compared to IHH transfected with the SIRT6 wild-type sequence. Several unsaturated fatty acids and glycerophospholipids were increased, and ceramide tended to be decreased upon SIRT6 N308K/A313S overexpression. Furthermore, we found that overexpression of SIRT6 N308K/A313S in a 3D hepatic spheroid model formed by the co-culture of human immortalized hepatocytes (IHH) and hepatic stellate cells (LX2) inhibited collagen deposition and fibrotic gene expression in absence of metabolic or dietary challenges. Hence, our findings suggest that novel longevity associated SIRT6 N308K/A313S variants could favor the prevention of NASH by altering hepatocyte proteome and lipidome.

Severe cerebrovascular pathology of the first supercentenarian to be autopsied in the world.

We report on a 116-year-old Japanese woman who was the first officially documented supercentenarian to be autopsied in the world. She lived a remarkably healthy life until suffering cerebral infarction at 109 years of age. She became Japan's oldest person at 113 years and died in 1995 from colon cancer at 116 years 175 days. Her medical records show the delayed onset of stroke, cancer, dementia, and heart disease and the importance of appropriate medical treatment and intensive dedicated care provided during the last stage of her life. She was the longest-lived person in Japan for 21 years from 1993 until 2014. The neuropathological findings of her autopsied brain were briefly reported in the Japanese literature in 1997. In this study, we reinvestigated her brain and spinal cord in more detail. Severe cerebrovascular lesions and cervical spondylotic myelopathy were found to be the main causes of her disability. Although the density of senile plaques was relatively high, the distribution of neurofibrillary tangles was limited. Ghost tangles and argyrophilic grains were mild. The mildness of tau pathological changes in her neurons, in other words the resistance of neurons to tau pathology, may be a factor responsible for her longevity.

Surgical treatment of proximal femoral fractures in centenarians: prevalence and outcomes based on a German multicenter study.

PURPOSE: This study aimed to estimate the survival rate after proximal femoral fracture insult and identify the subgroup of centenarians with a high risk. METHODS: Records of patients (≥ 65 years) who underwent surgery for PFF between 2006 and 2020 were retrieved from the electronic databases of three hospitals. Overall, 22 demographic, perioperative, and postoperative variables were analyzed for all patients > 99 years of age. The effect of anemia, time to surgery, surgical procedure, place of residence, and dementia on complications and survival were evaluated. RESULTS: The study included 85 patients (women n = 71; men n = 14; median age, 100 years; range 100-106 years). Over the study period, the prevalence of centenarians with PFF increased (0.94%). The overall complication rate was 28% (in-hospital death, n = 16; infection, n = 1; hematoma, n = 1; implant failure, n = 1; cardiac decompensation, n = 3; pneumonia with delirium, n = 1; urinary tract infection, n = 1). The 30-day, 3-month, 6-month, and 1-year mortality rates for the study group were 27.1%, 42.4%, 55.3%, and 61.2%, respectively. Median survival was 150 days (range 1-1942 days). Patients with dementia (n = 47) had a shorter survival time than patients without dementia (n = 38) (hazard ratio 1.75; 95% confidence interval 1.04, 2.95). Preoperative anemia, time to surgery, or necessary surgical procedure had no impact on survival. CONCLUSIONS: The prevalence of centenarians undergoing surgery for PFF is increasing. In-hospital mortality is high, and dementia is a risk factor impacting survival. The rates of surgical revision and general complications are low, and the chosen predictors had no significant impact on these outcomes. The survival rate after discharge from hospital seems to be comparable to the estimated survival rate of uninjured centenarians.

Cognition, function, and prevalent dementia in centenarians and near-centenarians: An individual participant data (IPD) meta-analysis of 18 studies.

INTRODUCTION: There are limited data on prevalence of dementia in centenarians and near-centenarians (C/NC), its determinants, and whether the risk of dementia continues to rise beyond 100. METHODS: Participant-level data were obtained from 18 community-based studies (N = 4427) in 11 countries that included individuals ≥95 years. A harmonization protocol was applied to cognitive and functional impairments, and a meta-analysis was performed. RESULTS: The mean age was 98.3 years (SD = 2.67); 79% were women. After adjusting for age, sex, and education, dementia prevalence was 53.2% in women and 45.5% in men, with risk continuing to increase with age. Education (OR 0.95;0.92-0.98) was protective, as was hypertension (odds ratio [OR] 0.51;0.35-0.74) in five studies. Dementia was not associated with diabetes, vision and hearing impairments, smoking, and body mass index (BMI). DISCUSSION: Among the exceptional old, dementia prevalence remains higher in the older participants. Education was protective against dementia, but other factors for dementia-free survival in C/NC remain to be understood.

Single-Cell Transcriptomics Reveals Longevity Immune Remodeling Features Shared by Centenarians and Their Offspring.

Centenarians, who show mild infections and low incidence of tumors, are the optimal model to investigate healthy aging. However, longevity related immune characteristics has not been fully revealed largely due to lack of appropriate controls. In this study, single-cell transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) derived from seven centenarians (CEN), six centenarians' offspring (CO), and nine offspring spouses or neighbors (Control, age-matched to CO) are performed to investigate the shared immune features between CEN and CO. The results indicate that among all 12 T cell clusters, the cytotoxic-phenotype-clusters (CPC) and the naïve-phenotype-clusters (NPC) significantly change between CEN and ontrol. Compared to Control, both CEN and CO are characterized by depleted NPC and increased CPC, which is dominated by CD8+ T cells. Furthermore, CPC from CEN and CO share enhanced signaling pathways and transcriptional factors associated with immune response, and possesse similar T-cell-receptor features, such as high clonal expansion. Interestingly, rather than a significant increase in GZMK+ CD8 cells during aging, centenarians show accumulation of GZMB+ and CMC1+ CD8 T cells. Collectively, this study unveils an immune remodeling pattern reflected by both quantitative increase and functional reinforcement of cytotoxic T cells which are essential for healthy aging.

A rare human centenarian variant of SIRT6 enhances genome stability and interaction with Lamin A.

Sirtuin 6 (SIRT6) is a deacylase and mono-ADP ribosyl transferase (mADPr) enzyme involved in multiple cellular pathways implicated in aging and metabolism regulation. Targeted sequencing of SIRT6 locus in a population of 450 Ashkenazi Jewish (AJ) centenarians and 550 AJ individuals without a family history of exceptional longevity identified enrichment of a SIRT6 allele containing two linked substitutions (N308K/A313S) in centenarians compared with AJ control individuals. Characterization of this SIRT6 allele (centSIRT6) demonstrated it to be a stronger suppressor of LINE1 retrotransposons, confer enhanced stimulation of DNA double-strand break repair, and more robustly kill cancer cells compared with wild-type SIRT6. Surprisingly, centSIRT6 displayed weaker deacetylase activity, but stronger mADPr activity, over a range of NAD+ concentrations and substrates. Additionally, centSIRT6 displayed a stronger interaction with Lamin A/C (LMNA), which was correlated with enhanced ribosylation of LMNA. Our results suggest that enhanced SIRT6 function contributes to human longevity by improving genome maintenance via increased mADPr activity and enhanced interaction with LMNA.

Frailty and Associated Factors among Chinese Centenarians.

OBJECTIVES: The study aimed to apply the frailty index (FI) to assess frailty status among Chinese centenarians and analyse its associated factors. DESIGN: The study was a cross-sectional study. SETTING AND PARTICIPANTS: The study included 1043 centenarians (742 females and 301 males) aged ≥100 years from the 2018 wave of the China Longitudinal Healthy Longevity Survey. MEASUREMENTS: All participants were assessed for frailty by the FI. Basic characteristics, including age, height, weight, calf circumference, waist circumference, hip circumference, sex, years of education, financial status, exercise, fall status, coresidence, smoking, alcohol consumption, number of natural teeth, denture use, toothache, and tooth brushing, were collected. Multivariate logistic regression was used to analyse the associations between risk factors and frailty. RESULTS: The average age of the participants was 102.06±2.55 years (range: 100-117 years). The FI ranged between 0.00 and 0.63. The mean FI for all participants was 0.27±0.13 (median 0.25; interquartile range 0.20-0.35). Participants were divided into quartiles. The number of natural teeth and denture use, coresidence, sex, exercise, and financial status showed significant associations with frailty classes (all P<0.05). Multivariate logistic regression analysis indicated that having ≤20 natural teeth without dentures (OR, 95% CI= 1.89(0.004-1.246), P<0.05), having ≤20 natural teeth with dentures (OR, 95% CI=2.21(0.158,1.432), P=0.015), living alone or in an institution (OR, 95% CI=1.68(0.182-0.849), P=0.002), lacking exercise (OR, 95% CI=2.54(0.616-1.246), P<0.001), having insufficient financial resources (OR, 95% CI=2.9(0.664-1.468), P<0.001), and being female (OR, 95% CI=1.47(0.137,0.634), P=0.002) were independent risk factors for frailty. CONCLUSION: Chinese centenarian women are frailer than men. Having fewer natural teeth, living alone or in an institution, lacking exercise, and having insufficient financial resources were the factors associated with frailty among Chinese centenarians. Family conditions and healthy lifestyles may be important for frailty status in centenarians.

Sex hormones and physical function among the Chinese oldest-old and centenarian women.

BACKGROUND: Physical independence is crucial for overall health in the elderly individuals. The life expectancy of women has been shown to be higher than that of men, which is also known as the "male-female health-survival paradox". Sex hormones may be one of the explanations. However, the relationships between sex hormones and physical function remain unclear in the elderly females. This study was designed to explore these relationships among the Chinese oldest-old and centenarian women. METHODS: Data from 1226 women were obtained from the China Hainan Centenarian Cohort Study. Home interviews, physical examinations and blood analyses were conducted using standardized procedures. Variables including age, Han ethnicity, illiteracy, smoker, drinker, estradiol (E2), testosterone (T), follicle-stimulating hormone, and luteinizing hormone were used in the multivariate logistic and linear regression analyses. RESULTS: In all the participants, age [beta (95% confidence interval): - 0.84 (- 0.98, - 0.71)] and E2 levels [beta (95% confidence interval): - 0.22 (- 0.28, - 0.17)] were negatively associated with activities of daily living (ADLs) in the multivariate linear regression analyses (P < 0.05 for all). We also observed significantly negative associations of age [odds ratio (95% confidence interval): 0.90 (0.88, 0.91)] and E2 levels [odds ratio (95% confidence interval): 0.98 (0.98, 0.99)] with physical normality in the multivariate logistic regression analyses (P < 0.05 for all). Age and E2 levels gradually decreased with increases in the ADL quartiles across all the participants (P < 0.05 for all). CONCLUSIONS: This study demonstrated that E2 levels were negatively associated with physical function among the Chinese oldest-old and centenarian women.

Higher ATM expression in lymphoblastoid cell lines from centenarian compared with younger women.

With increased life expectancies in developed countries, cancer rates are becoming more common among the elderly. Cancer is typically driven by a combination of germline and somatic mutations accumulating during an individual's lifetime. Yet, many centenarians reach exceptionally old age without experiencing cancer. It was suggested that centenarians have more robust DNA repair and mitochondrial function, allowing improved maintenance of DNA stability. In this study, we applied real-time quantitative PCR to examine the expression of ATM in lymphoblastoid cell lines (LCLs) from 15 healthy female centenarians and 24 younger female donors aged 21-88 years. We observed higher ATM mRNA expression of in LCLs from female centenarians compared with both women aged 21-48 years (FD = 2.0, p = .0016) and women aged 56-88 years (FD = 1.8, p = .0094. Positive correlation was found between ATM mRNA expression and donors age (p = .0028). Levels of hsa-miR-181a-5p, which targets ATM, were lower in LCLs from centenarians compared with younger women. Our findings suggest a role for ATM in protection from age-related diseases, possibly reflecting more effective DNA repair, thereby reducing somatic mutation accumulation during aging. Further studies are required for analyzing additional DNA repair pathways in biosamples from centenarians and younger age men and women.