Centenarian Study Research Articles

Lipid profile in elderly and centenarian subjects in Kazakhstan: a case-control study

Introduction. The health of centenarians is a major focus in global studies. Dyslipidemia is directly linked to the risk of cardiovascular diseases, which pose a growing burden on healthcare due to the increasing elderly population. Studying the lipid profiles of centenarians is important for preventing circulatory system diseases and promoting healthy aging. This research aims to compare the prevalence of dyslipidemia in centenarians (median age 96 [95-97]) with elderly individuals (median age was 69 [64 – 74]) in the Republic of Kazakhstan and examine potential predictors of dyslipidemia in the centenarian group. Methods. The study involved 46 centenarians (study group) and 82 elderly individuals (control group). Statistical analysis was used to process the data, including blood markers and demographic variables, to identify factors contributing to dyslipidemia. Results and conclusion. The prevalence of hypercholesterolemia in centenarians was 32.6% (15 people - 3 men; 12 women), with elevated LDL levels in 4.3% (2 women). In the control group, hypercholesterolemia prevalence was 29.3% (24 people - 6 men; 18 women) and elevated triglycerides in 6.1% (3 women; 2 men). The study and control groups were compared based on their lipid profile characteristics, which showed similarities as indicated by all p-values being above 0.05: Cholesterol (p=0.348), HDL (p=0.975), LDL (p=0.161), and Triglycerides (p=0.159). Decreased physical activity was a predictor of dyslipidemia in centenarians. Excessive cholesterol levels were significantly higher among women than men in both groups. The primary factor for dyslipidemia was low physical activity, with other predictors having no significant impact on the lipid profiles of centenarians. This factor should be considered when assessing cardiovascular disease risks and all-cause mortality.

Cross-sectional association between high-sensitivity C-reactive protein and cognitive function in community-dwelling older adults: the SONIC study

BackgroundA decline in cognitive function is associated with inflammatory processes. However, the association between high-sensitivity C-reactive protein (hs-CRP) levels and cognitive decline in the Japanese population remains inconclusive. Thus, this study aimed to determine whether hs-CRP is associated with low cognitive function in 70- and 80-year-old community-dwelling Japanese individuals.MethodsThe participants in this cross-sectional study were 872 Japanese residents aged 70 and 80 years who voluntarily participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study between 2010 and 2011. Blood sample collection, cognitive assessment, and other measurements were performed at the venue. Low cognitive function was defined as a score of 25 points or lower on the Japanese version of the Montreal Cognitive Assessment. The odds ratio (OR) and 95% confidence interval (95% CI) for each hs-CRP quartile were calculated using logistic regression analysis.ResultsA total of 288 (69.9%) parsons in the 70-year-old group and 372 (80.9%) in the 80-year-old group exhibited low cognitive function. The association between hs-CRP levels and low cognitive function was significant among 70- and 80-year-old Japanese community-dwelling adults. In particular, the fourth quartile of hs-CRP (0.727–7.420 mg/L) in the 70-year-old group and the second and fourth quartiles (0.214–0.404 and 0.911–9.890 mg/L) in the 80-year-old group were associated with low cognitive function. Furthermore, the third quartile (0.409–0.892 mg/L) in the 80-year-old group was closely associated with low cognitive function.ConclusionsHigh hs-CRP levels were associated with lower cognitive function in 70- and 80-year-old Japanese community-dwelling individuals, suggesting that high hs-CRP levels may influence cognitive function.

Relationship between respiratory function assessed by spirometry and mild cognitive impairment among community-dwelling older adults.

Aging is a major cause of cognitive dysfunction. It has also been reported that respiratory function may influence cognitive dysfunction. However, few studies have examined the relationship between cognitive function and respiratory function among community-dwelling older adults. This study aims to determine the relationship between respiratory function, assessed using spirometry, and mild cognitive impairment (MCI) in community-dwelling older adults. This study included 419 participants aged 73 ± 1 years and 348 participants aged 83 ± 1 years from the SONIC cohort study (Septuagenarians Octogenarians Nonagenarians Investigation with Centenarians Study). Respiratory function was evaluated using %Vital Capacity (%VC), Forced Expiratory Volume 1 s (FEV1)/Forced Vital Capacity (FVC), and %Peak Expiratory Flow (%PEF). Airflow-limitation presence and stages were classified using FEV1/FVC. Cognitive function and MCI were assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). The MoCA-J score exhibited a declining trend as the airflow-limitation stage increased among study participants in the 83 ± 1 age group. The presence of airflow limitation was associated with MCI in the 83 ± 1 age group. Among the indicators of each respiratory function, low %PEF was found to be associated with an increased rate of MCI. Furthermore, low %VC has also been suggested to be associated with an increased rate of MCI in the 83 ± 1 age female group. Advanced airflow-limitation stages may exacerbate cognitive dysfunction in community-dwelling older adults. The presence of airflow limitation and low %VC may also be associated with cognitive dysfunction in older women. Consequently, reduced respiratory function may potentially be associated with MCI in community-dwelling older adults. Geriatr Gerontol Int 2024; 24: 1001-1007.

Associations between Brain Alpha-Tocopherol Stereoisomer Profile and Hallmarks of Brain Aging in Centenarians.

Brain alpha-tocopherol (αT) concentration was previously reported to be inversely associated with neurofibrillary tangle (NFT) counts in specific brain structures from centenarians. However, the contribution of natural or synthetic αT stereoisomers to this relationship is unknown. In this study, αT stereoisomers were quantified in the temporal cortex (TC) of 47 centenarians in the Georgia Centenarian Study (age: 102.2 ± 2.5 years, BMI: 22.1 ± 3.9 kg/m2) and then correlated with amyloid plaques (diffuse and neuritic plaques; DPs, NPs) and NFTs in seven brain regions. The natural stereoisomer, RRR-αT, was the primary stereoisomer in all subjects, accounting for >50% of total αT in all but five subjects. %RRR was inversely correlated with DPs in the frontal cortex (FC) (ρ = -0.35, p = 0.032) and TC (ρ = -0.34, p = 0.038). %RSS (a synthetic αT stereoisomer) was positively correlated with DPs in the TC (ρ = 0.39, p = 0.017) and with NFTs in the FC (ρ = 0.37, p = 0.024), TC (ρ = 0.42, p = 0.009), and amygdala (ρ = 0.43, p = 0.008) after controlling for covariates. Neither RRR- nor RSS-αT were associated with premortem global cognition. Even with the narrow and normal range of BMIs, BMI was correlated with %RRR-αT (ρ = 0.34, p = 0.021) and %RSS-αT (ρ = -0.45, p = 0.002). These results providing the first characterization of TC αT stereoisomer profiles in centenarians suggest that DP and NFT counts, but not premortem global cognition, are influenced by the brain accumulation of specific αT stereoisomers. Further study is needed to confirm these findings and to determine the potential role of BMI in mediating this relationship.

Association between serum vitamin D levels and skeletal muscle indices in an older Japanese population: The SONIC study.

Vitamin D (VD) affects skeletal muscles. The high prevalence of VD deficiency in Japan may lead to decreased skeletal muscle mass and strength, increasing the prevalence of sarcopenia. Therefore, we aimed to investigate the association between serum VD levels and skeletal muscle indices in a Japanese community-dwelling older population. We extracted data from the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study. We analyzed the data for participants in the 70s and 90s age groups. Skeletal mass index (SMI) using bioimpedance analysis, grip strength, walking speed, and serum VD levels using 25-hydroxyvitamin D [25(OH)D] were measured. We analyzed the data of 310 participants in their 70s and 48 in their 90s. Mean serum 25(OH)D levels were 21.6 ± 5.0 ng/mL in the 70s group and 23.4 ± 9.1 ng/mL in the 90s group. In the 70s group, serum 25(OH)D levels correlated with SMI (r = 0.21, P < 0.0001) and grip strength (r = 0.30, P < 0.0001). Serum 25(OH)D levels were independently associated with SMI after adjusting for sex, body mass index, and serum albumin levels. In the 90s group, serum 25(OH)D levels were correlated with SMI (r = 0.29, P = 0.049) and grip strength (r = 0.34, P = 0.018). However, the multivariate analysis showed no independent association between SMI, grip strength, and serum 25(OH)D levels. In a cross-sectional analysis of an older population, serum VD levels were associated with SMI and grip strength, and this association was more pronounced in the 70s group than in the 90s group. Our results suggest that serum VD levels maintain skeletal muscle mass and grip strength. Geriatr Gerontol Int 2024; ••: ••-••.

Risk factors predicting subtypes of physical frailty incidence stratified by musculoskeletal diseases in community-dwelling older adults: The SONIC study.

This study aims to identify the key risk factors that lead to subtypes of physical frailty assessed by walking speed and grip strength among community-dwelling Japanese individuals, stratified by the presence of musculoskeletal diseases (MSDs) and age group. We included 302 participants aged 70 or 80 years who did not exhibit subtypes of physical frailty at baseline through the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians (SONIC) study. Our study was a longitudinal study. The outcome was the incidence of subtypes of physical frailty after 3 years. Subtypes of physical frailty were defined as a weak grip strength or slow walking speed, or both, based on the Japanese version of the Cardiovascular Health Study Index. The risk factors for subtypes of physical frailty incidence were examined by age group and MSD, using multivariate logistic regressions. Of the 302 participants, 110 (36.4%) had MSD. Those with MSD were significantly more likely to have subtypes of physical frailty after 3 years compared with those without MSD. Among all participants, older age was a risk factor of subtypes of physical frailty (P < 0.05). Without MSD, older age and dissatisfied financial status were risk factors (P < 0.05). With MSD, older age was a risk factor (P < 0.05). By age group, in individuals aged 70 years old, a dissatisfied financial status was a risk factor for those without MSD (P < 0.05), and a higher BMI was one for those with MSD (P < 0.05). Older age was a risk factor for subtypes of physical frailty, but other risk factors differed according to the presence of MSD and age. Geriatr Gerontol Int 2024; 24: 797-805.

Adherence to the Alternative Health Eating Index and Planetary Health Diet Index in the New England Centenarian Study

Adherence to the Alternative Health Eating Index and Planetary Health Diet Index in the New England Centenarian Study

Positive Aspects of Caregiving in Familial Care for Nonagenarians and Centenarians: Findings from Hong Kong Centenarian Study.

Caregiving for the fast-growing but vulnerable oldest-old population may involve distinct challenges but also gratification. We analyzed quantitative and qualitative data from family caregivers of community-dwelling older adults aged 95 or above in Hong Kong. Quantitative analysis of 143 caregivers revealed that higher age, dependence on basic activities of daily living, independence on instrumental activities of daily living, and intact hearing ability of the older adults, and absence of a domestic helper and better self-rated health of the caregivers were associated with more positive aspects of caregiving. Qualitative analysis of the 96 caregivers who mentioned at least a positive aspect from their caregiving identified three themes: acquiring caregiving skills, fulfilling family love and obligation, and preparing for graceful aging. Our findings elaborated the nature and mechanism of caregiving gains against the unique backdrop of exceptional longevity and the Chinese cultural expectations of filial piety.

Effects of multimorbidity and polypharmacy on physical function in community-dwelling older adults: A 3-year prospective cohort study from the SONIC

BackgroundWe prospectively examined the effect of baseline multimorbidity and polypharmacy on the physical function of community-dwelling older adults over a three-year period. MethodsThe analysis included 1,401 older adults (51.5 % women) who participated in both wave 1 and wave 2 (3-year follow-up) of the Septuagenarians, Octogenarians, and Nonagenarians Investigation with Centenarians (SONIC) study. Grip strength and walking speed were binarized into poor/not poor physical function according to the frailty definition. The number of chronic conditions and the number of prescribed medications were categorized into 3 and 4 groups, respectively. Multivariable logistic regression was used to examine associations between the number of chronic conditions, medication use at baseline, and poor physical function over a three-year period. ResultsAfter adjusting for confounding factors, hyperpolypharmacy (≥ 10 medications) demonstrated associations with weak grip strength (adjusted odds ratio [aOR] = 2.142, 95 % confidence interval [CI] = 1.100–4.171) and slow walking speed (aOR = 1.878, 95 % CI = 1.013–3.483), while co-medication (1–4 medications) was negatively associated with slow walking speed (aOR = 0.688, 95 % CI = 0.480–0.986). There was no significant association between the number of chronic conditions and physical function. ConclusionThe findings suggest that the number of medications can serve as a simple indicator to assess the risk of physical frailty. Given that many older individuals receive multiple medications for extended durations, medical management approaches must consider not only disease-specific treatment outcomes but also prioritize drug therapy while actively avoiding the progression towards frailty and geriatric syndromes.

YQTL Pipeline: A structured computational workflow for large scale quantitative trait loci discovery and downstream visualization.

Quantitative trait loci (QTL) denote regions of DNA whose variation is associated with variations in quantitative traits. QTL discovery is a powerful approach to understand how changes in molecular and clinical phenotypes may be related to DNA sequence changes. However, QTL discovery analysis encompasses multiple analytical steps and the processing of multiple input files, which can be laborious, error prone, and hard to reproduce if performed manually. To facilitate and automate large-scale QTL analysis, we developed the yQTL Pipeline, where the 'y' indicates the dependent quantitative variable being modeled. Prior to the association test, the pipeline supports the calculation or the direct input of pre-defined genome-wide principal components and genetic relationship matrix when applicable. User-specified covariates can also be provided. Depending on whether familial relatedness exists among the subjects, genome-wide association tests will be performed using either a linear mixed-effect model or a linear model. The options to run an ANOVA model or testing the interaction with a covariate are also available. Using the workflow management tool Nextflow, the pipeline parallelizes the analysis steps to optimize run-time and ensure results reproducibility. In addition, a user-friendly R Shiny App is developed to facilitate result visualization. It can generate Manhattan and Miami plots of phenotype traits, genotype-phenotype boxplots, and trait-QTL connection networks. We applied the yQTL Pipeline to analyze metabolomics profiles of blood serum from the New England Centenarians Study (NECS) participants. A total of 9.1M SNPs and 1,052 metabolites across 194 participants were analyzed. Using a p-value cutoff 5e-8, we found 14,983 mQTLs associated with 312 metabolites. The built-in parallelization of our pipeline reduced the run time from ~90 min to ~26 min. Visualization using the R Shiny App revealed multiple mQTLs shared across multiple metabolites. The yQTL Pipeline is available with documentation on GitHub at https://github.com/montilab/yQTLpipeline.

Very old age impacts masticatory performance: a study among sexagenarians to centenarians

ObjectiveThis cross-sectional pilot study evaluated the impact of age on masticatory performance among individuals aged 65 to 106 years, as part of the Heidelberg Dental Centenarian Study (HD-100Z) conducted in South-Western Germany.Materials and methodsA total of 31 centenarians were recruited, alongside 31 individuals each from the age groups 75–99 and 65–74, matched based on sex, prosthetic status, and number of teeth. Masticatory performance was assessed using a two-colored chewing gum test and digital image processing. Multiple linear regression analysis was performed to assess the effect of age, sex, number of teeth, type of prosthesis on the masticatory performance.ResultsMasticatory performance, as measured by the standard deviation of hue in the chewing gum test, decreased significantly in centenarians compared to individuals aged 75–99 years (-0.112, p = 0.037) and those aged 65–74 years (-0.274, p < 0.001). The effects of sex, number of teeth, and type of prosthesis on masticatory performance were not significant associations (p ≥ 0.135).ConclusionThe findings suggest that age may have a significant influence on masticatory performance in the studied age groups, challenging previous notions that aging itself has little impact on masticatory ability. The inclusion of centenarians in the study highlights the need for further investigation into masticatory function in age groups reaching up to 100 years or more.Clinical relevanceThis study contributes to the understanding of how ageing affects oral function, which may guide dental treatment approaches for older individuals, and set the stage for more in-depth investigations in this field in the future.

Profiles of centenarians’ functioning: linking functional and cognitive capacity with depressive symptoms

BackgroundDespite most centenarians facing age-related declines in functional and cognitive capacities, the severity of these declines varies among individuals, as does the maintenance of good mental health (e.g., depressive symptoms) despite these declines. This study aims to examine this heterogeneity in centenarians from the Second Heidelberg Centenarian Study, which collected data from 112 centenarians living in Germany. In our study, we focus on a subsample of 73 centenarians who provided self-reports for our measures of interest (M age = 100.4, SD age = 0.55).MethodsWe examined correlations between functional capacity (i.e., PADL, IADL), cognitive capacity (i.e., MMSE), and depressive symptoms (i.e., GDS), and the existence of different profiles using hierarchical clustering.ResultsHigher functional capacity was related to higher cognitive capacity and to fewer depressive symptoms. Yet, higher cognitive capacity was associated with more depressive symptoms. Hierarchical clustering analysis elucidated this contradiction by identifying three profiles: low-capacity individuals (i.e., 24 individuals had low functional and cognitive capacities, with low depressive symptoms), high-capacity individuals (i.e., 33 individuals with high functional and cognitive capacities, with low depressive symptoms), and low-functional-high-cognitive-capacity individuals (i.e., 16 individuals showed low functional but high cognitive capacity, with high depressive symptoms). Our post-hoc analyses highlighted arthritis and pain as risk factors for functional dependence and depression.ConclusionsOur findings emphasize the importance of identifying centenarian subgroups with specific resource- and risk profiles to better address their needs, and of treating pain to improve functional capacity and mental health in centenarians.

Usefulness of the serum creatinine/cystatin C ratio as a blood biomarker for sarcopenia components among age groups in community-dwelling older people: The SONIC study.

The serum creatinine/cystatin C ratio (CCR) or sarcopenia index is considered a useful marker of muscle mass. However, its usefulness in late-stage older adults remains unclear. We aimed to determine the usefulness of CCR as an indicator of sarcopenia in community-dwelling Japanese adults aged >75 years. Our study recruited participants aged 70, 80, and 90 ± 1 years during the baseline years, and included a 3-year follow-up in the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians study. From 2015 to 2018, 955 participants were eligible: 367 in their 70s, 304 in their 80s, and 284 in their 90s. The diagnostic components of sarcopenia, including "low muscle mass, plus low muscle strength, and/or low physical performance," were evaluated using the bioelectrical impedance analysis-measured skeletal muscle mass index (SMI), handgrip strength, and short physical performance battery (SPPB) score, respectively, in accordance with the Asia Working Group for Sarcopenia 2019 criteria. Separate analyses were performed between each component and CCR, adjusting for sex, body mass index, and other blood biomarkers in each group. The relationship between CCR and sarcopenia components was significant for handgrip strength (β = 0.21, 0.13, 0.19, and P < 0.0001, =0.0088, <0.0001, for the 70s, 80s, and 90s age groups, respectively); however, it was limited for SMI (β = 0.14; P = 0.0022, only for the 90s) and not significant for the SPPB score. CCR is a limited indicator of sarcopenia in late-stage older adults. Although its association with muscle strength was significant, its relationship with muscle mass and physical performance was less pronounced. Geriatr Gerontol Int 2024; 24: 529-536.

Effect of number of medications on the risk of falls among community-dwelling older adults: A 3-year follow-up of the SONIC study.

This study examined the association between the number of prescribed medications and falls among community-dwelling older adults. We conducted a geriatric comprehensive health-checkup on community-dwelling adults aged 69-91 years who participated in the Septuagenarians, Octogenarians, and Nonagenarians Investigation with Centenarians study. The final analysis of this study included 1,076 participants with complete data. The participants were divided into four groups based on the number of medications at baseline: 0, 1, 2-4, and ≥5. At the 3-year follow-up, the participants were asked whether they had fallen in the past year. Multivariable logistic regression analysis was performed to assess the relationship between the number of medications taken and falls after adjusting for confounding factors. The prevalence rates of falls were 10.5%, 18.2%, 18.3%, and 19.8% in the no-medication, one-medication, comedication, and polypharmacy groups, respectively. In the one-medication prescription group, 59% of prescriptions were for fall-risk-increasing drugs (FRID). Multivariable analysis showed a significantly higher incidence of falls in the one-medication group (adjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.04-3.54), co-medication (OR, 1.89; 95% CI, 1.09-3.29), and polypharmacy groups (OR, 1.94; 95% CI, 1.09-3.45) than in the no-medication group. The study showed that polypharmacy, as well as just taking one medication, can affect the occurrence of falls. This suggests that in addition to the number of medications and polypharmacy, the type of medication, such as FRID, affects the risk of falls. Therefore, pharmacotherapy should consider the risk of falls in older adults when prescribing medications. Geriatr Gerontol Int 2024; 24: 306-310.

INTRODUCING CENTENARIAN STUDIES IN AN AGING WORLD

Abstract Centenarian studies have come of age. With the first comprehensive centenarian studies conducted more than 35 years ago, there are now centenarian databases in the United States, in Europe, and in Asian countries. The major focus of these studies has been on genetic and family longevity factors, on support systems, personality, and on health behaviors. Another emphasis has been on various health components, such as physical health, mental health, frailty, and psychological well-being. In recent years, a second generation of centenarian studies has been initiated, comparing earlier born cohorts with later born cohorts. Among the first studies conducting a cohort comparison, the Danish centenarian studies, the Georgia centenarian studies, and the Tokyo centenarian studies showed inconsistent results. Whereas some studies indicated that later born cohorts enjoyed higher levels of functioning (e.g., Denmark, U.S. Georgia), other studies showed poorer performance (e.g., Japan). The current symposium sheds additional light on cohort comparisons with recently collected data from the second Hong Kong Centenarian Study, the Kyotango centenarian cohort, and the Health and Retirement Study. This presentation summarizes major findings from centenarian studies conducted around the world and highlights activities of the International Consortium of Centenarian Studies (ICC).

PROFILES OF TWO COHORTS OF NEAR-CENTENARIANS AND CENTENARIANS: FINDINGS FROM HONG KONG CENTENARIAN STUDY 1 AND 2

Abstract Hong Kong launched its first centenarian study in 2011 when there were just over 3,600 centenarians, and subsequently, the second phase in 2021/22 when the population of centenarians tripled. Both studies investigated the multidimensional well-being of local older adults of Chinese ethnicity aged 95 or above (near centenarians and centenarians, NCCs). A comparison of the two cohorts of community dwelling NCCs who lived with their family (2011: N=77; 2021/22: N=151) indicates a substantial drop in sensory functions (2011 vs 2021/22: intact vision: 94.8% vs 40.4%; intact hearing: 93.5% vs 53.6%), social activities (weekly or more: 48.1% vs 40.4%), outdoor activities (weekly or more: 75.3% vs 45.3%), and independence in activities of daily living (ADL) (no. of dependent task: 0.79 vs 2.79). Although the prevalence of comorbidities was comparable (Charlson age-adjusted comorbidity index: Mean = 2.7 vs 3.5), the frailty and pre-frailty was considerably more common in the 2021/22 cohort (55.3%; 39.0%) than the 2011 cohort (50.6%; 23.4%). We also found disparate predictors for health evaluations. Among the 2011 cohort, being male and having better psychological well-being were related to more favorable assessments of health compared to their peers. Among the 2021/22 cohort, favorable peer-compared health assessments were related to fewer ADL dependent tasks, better psychological well-being, higher age and being female. Despite the impact by COVID on the 2021/22 cohort, our findings alert policy makers and practitioners worldwide to the growing number of community-dwelling adults of advanced age with considerable personal care and health needs.

GETTING BETTER OR GETTING WORSE: MARKERS OF LONGEVITY ACROSS COHORTS AND COUNTRIES

Abstract The expansion of life expectancy and the lengthening of the human life span are extraordinary achievements observed over the last century. Among those accomplishments is the increasing number of centenarians in many countries. However, it is not clear whether new cohorts of centenarians are in better health when compared to earlier born cohorts of centenarians. The purpose of this symposium is to compare centenarian cohorts across different countries. Two centenarian cohorts each from Hong Kong, Japan, and the United States are included in the analyses. Results provide different perspectives across countries. The Hong Kong Centenarian Studies compared current centenarians to those who participated at an earlier time and noted that proxies in the second study rated centenarians in worse health when compared to centenarian self-ratings. The Kyotango study assessed living conditions, care need level, ADL, IADL, and cognitive function by gender and noted cognitive improvement for men. Finally, later cohorts of the U.S. Health and Retirement Study were in worse health when compared to the earlier born cohort. The results provide an indication for policy makers and practitioners who will prepare for a larger number of centenarians in need of additional support. Although some improvement for later born cohorts is noticeable, it is obvious that more care provision will also be needed as centenarians around the world will survive with more health conditions. Additional research should evaluate centenarians in other parts of the world.

CHALLENGES OF VERY LATE LIFE: PHYSICAL AND MENTAL HEALTH, CAREGIVING, AND AGING PERCEPTIONS

Abstract The very old are the fastest growing population in developed countries, yet research on this age group remains limited. There are, however, specific challenges of very old age that differ from those in earlier late life phases. Very old individuals and their families may thus have unique needs and may require adapted services. In this symposium, we address selected challenges associated with reaching very old age, including physical and mental health issues, as well as implications of both receiving and providing care. Ribeiro and colleagues report on centenarians’ health and morbidity profiles using the Portuguese census, by comparing individuals aged 100 years old in 2011 and 2021. Jopp and colleagues present findings from the first national Swiss centenarian study on centenarians’ health, cognition, and well-being. Gomes da Rocha and colleagues investigate depressive symptoms in Swiss centenarians during the COVID-19 pandemic, showing notably elevated scores. Kim and colleagues focus on aging perceptions and their correlates among dyads of very old parents and their old children from South Korea, highlighting the impact of the care experience for both dyad members. Gallagher and colleagues examine how old children of very old parents with dementia manage behavioral and psychological symptoms through specific strategies, offering insights on how to better support family care givers of very old dementia patients. In sum, this symposium offers novel insights on specific challenges encountered in very old age, by the individual and their families, and proposes potential pathways towards better understanding and handling of such challenges.

SERUM METABOLOMICS SIGNATURES OF EXTREME OLD AGE AND LONGEVITY

Abstract A total of 1,495 chemicals including 1,213 compounds of known identity and 282 compounds of unknown structural identity were profiled in serum samples collected at enrollment at Metabolon, Inc. from the blood serum of 213 subjects, including centenarians (n=80), offspring (n=70), and controls (n=63), mean ages of 105, 70, and 70, respectively, enrolled in the New England Centenarian Study (NECS). We performed metabolite- and metabolite module-based regression analyses on age, differential analyses comparing centenarian to offspring and control, and Cox proportional hazard-based survival analyses. We annotated the derived signatures by enrichment analysis using metabolite sets curated by Metabolon, RefMet, and Pathbank, among others. We identified 323 (436) metabolites that change with age at an FDR-corrected q-value of 0.01 (0.05), and 298 (407) metabolites differentially abundant between centenarians, their younger offspring, and controls. Our results confirm and expand upon previous metabolomics-based studies of aging, including decreased abundance with age of Tryptophan, DHEA-S, Pregnenolone, Glutathione, and Androgen, among others, and increased abundance of Amino acids (Tyrosines), Phenylacetylglutamine, Ornithine, Urea, Kynurenine, and Creatine, among others. To distinguish metabolites associated with longevity from those associated with extreme old age, we performed age-adjusted survival analysis, and rank-based enrichment analysis identified several metabolites significantly associated with survival independent of age, including secondary and primary (C 24) bile acids, and multiple classes of steroids (androgens, pregnenolone, progestin), among others. Additional analyses are ongoing to further annotate and characterize these findings. If validated, these results could contribute to the identification of novel healthy aging therapeutics.

Clinical research on extreme longevity: The FACET experience

People with extreme longevity represent a unique model to study the biology of aging. Unfortunately, their inclusion in research projects is challenging with the consequent lack of evidence and the need to rely on small convenience samples. Given the growing global aging population, especially in the segment of the oldest old (i.e., aged 90 and older), research in this population has become crucial. Furthermore, by studying the characteristics of extremely longeval persons, it might be possible to 1) better understand the mechanisms of aging, and 2) identify endogenous or exogenous factors contributing to a long life. The design and implementation of research activities in the oldest people need special consideration and a pragmatic approach. Possible implementable solutions and suggestions are provided from experience gained during the conduction of the FAtigue in CEnTenarians (FACET) study.