1,077 pubs · 81,550 cites · h-index 140
The Journals of Gerontology Series ASemelka et al.cohort
Higher and increasing levels of pro-inflammatory senescence-associated secretory phenotype (SASP) biomarkers are associated with poorer baseline physical function and impaired functional recovery at 3 months in older adults hospitalized for acute decompensated heart failure.
The Journals of Gerontology Series ADubé et al.Cross-Sectional Study
BACKGROUND: Aging is accompanied by changes in body composition and cognition. Although adiposity has been linked to metabolic dysfunction and dementia risk, associations with specific cognitive domains in later life remain unclear. METHODS: This cross-sectional study examined associations between adiposity and cognitive performance in 769 community-dwelling, healthy older adults (70-94 years) from the Study of Muscle, Mobility and Aging (SOMMA). Adiposity was assessed using anthropometric measures (body mass index, waist circumference) and MRI-derived regional fat volumes, including visceral and abdominal subcutaneous adipose tissue. Cognitive performance was evaluated using a screening measure (Montreal Cognitive Assessment), processing speed (Digit Symbol Coding Test), executive function (Trail Making Test B), and memory (California Verbal Learning Test-II Short Form). Multivariable linear regression models were sequentially adjusted for demographic, cardiometabolic, psychosocial, and behavioral factors. RESULTS: Greater age was associated with lower adiposity and poorer cognitive performance (p < 0.05). Most adiposity measures were inversely associated with processing speed after adjustment for age, sex, race, and testing site (p < 0.05). These associations generally persisted after adjustment for cardiometabolic conditions and were attenuated after inclusion of education, depressive symptoms, and behavioral covariates. No significant associations were observed between adiposity and executive function. Memory outcomes showed modest, exploratory associations with abdominal subcutaneous adipose tissue measures only in fully adjusted models (p = 0.03-0.07). CONCLUSIONS: In healthy older adults, adiposity is most consistently related to processing speed, whereas associations with memory and executive function are weaker or absent. Processing speed may be especially sensitive to adiposity-related differences. Longitudinal studies are needed to clarify temporal relationships.
GeroScienceGuida et al.RCT
Pooled analysis of randomized trials shows caloric restriction slows biological aging in older adults, indicating benefits extend beyond simple weight loss.
JACCKalogeropoulos et al.cohort
Hypothesis-generating for inflammation in incident HF; leaves open whether targeting IL-6 or TNF-α alters risk in older adults.
Contemporary Clinical TrialsNeiberg et al.Original Research
BACKGROUND: To implement strategies for enhancing research participation across a broad range of personal characteristics, additional data are needed regarding the degree of underrepresentation of specific individuals in research. METHODS: This study analyzed data from 3671 older (mean age 69 yrs) individuals enrolled in 19 studies conducted from 2002 to 2023 at Wake Forest University School of Medicine. Study inclusion was limited to those with a minimum age eligibility of 50 years. Demographic data of enrolled participants were compared to 1) individuals phone screened for participation and 2) US Census data of older individuals residing in the zip codes of the catchment area. RESULTS: There were 11 studies with screening data available, and the overall enrollment yield was 11.1% (n = 2207 of n = 19,895 screened). Those enrolled were similar in age to those who screened out, and a greater proportion of males (14.5%) versus females (12.4%) and White (22.3%) versus Black participants (19.4%) were enrolled after screening. Compared to Census estimates of older adults, individuals that were 75+ years at enrollment were underrepresented (Census 29%, enrolled 18%; PPR = 0.6), older adults with at least some college education were overrepresented (Census 24%, enrolled 80%; PPR = 3.27) and individuals who specified Black or African American ethnicity were slightly overrepresented (Census 14%, enrolled 19%; PPR = 1.31). Older adults who were 65 years or older, female, or had White ethnicity had proportional representation at enrollment. CONCLUSIONS: The research participants included across these studies had underrepresentation of adults older than 75 years and overrepresentation of college-educated and Black or African American race.
Aging CellMcIntyre et al.Original Research
Life is a constant struggle against disorder. As we age, our ability to maintain internal order declines. In the healthy human brain, order is observable in the form of functionally segregated brain network communities that exhibit spatial consistency. These communities associate with distinct cognitive and physical functions. When mapped into the brain, they form a functional "landscape". We assessed the spatial disorder of these landscapes in older adults with a wide range of mobility using a spatial form of Shannon entropy. We found that compared to younger adults, older adults had significantly higher entropy in the sensorimotor cortex, basal ganglia, hippocampus, thalamus, and occipital lobe. Higher entropy in many of these regions was associated with worse physical function and higher body mass index in older adults. Findings suggest that spatial entropy in brain network landscapes may be a marker of declining physical function. Modifiable factors, such as losing excess weight, may help to ameliorate aging-related brain entropy increases in regions such as the sensorimotor cortex, which may in turn help to preserve physical function in older adults.
Mau et al.Original Research
Reveals that greater pain is linked to longer walk and stair climb time in older adults, indicating significant impacts on mobility.
Mao et al.Cohort Study
Cohort study links eating window to mortality in adults, suggesting optimal duration to lower risk.
Contemporary Clinical TrialsStowe et al.Original Research
Pilot study randomized older adults to caloric restriction or time restricted eating interventions, highlighting specialized recruitment strategies.
Journal of the American Geriatrics SocietyThompson et al.Meta-Analysis
We appreciate the opportunity to respond to the thoughtful points raised by Professors Al Hamad and Sathian in their letter entitled, “Limitations in the additive risk model linking visual impairment and poor mobility to mortality.” As we explained in our brief report [1], the proportional hazards model which tested for interaction did not detect a significant synergistic interaction on the log hazards scale between initial overall visual impairment and impaired mobility (assessed utilizing the short physical performance battery [SPPB]) for the outcome of mortality (aHR 1.47, 95% CI [1.29, 1.67] in those with SPPB ≥ 9; aHR 1.47, 95% CI [1.00, 2.17] in those with SPPB < 9; p = 0.98). Thus, the factors in this particular model remained additive on the log hazards scale, though were not synergistic (i.e., did not have an effect more than expected by summing their individual effects). Although Al Hamad and Sathian reference another study by Xu et al. (2025) which applied mediation analysis to examine the association between self-reported visual difficulty at baseline (no visual difficulty vs. visual difficulty) and self-reported recurrent falls in the last year on mortality in the National Health and Aging Trends Study [2], we do not agree that this means our findings are contradictory with theirs, as a performance-based measure such as low SPPB score is not the same term as self-reported recurrent falls. Self-reported visual difficulty also has been shown to be poorly predictive of performance-based visual impairment using eye charts and should not be used to substitute for an objective measure [3]. Thus, we had different measurements, objective versus subjective, and were not examining the same factors related to physical function. Moreover, we tested for interaction. We intentionally did not test for mediation because vision was only evaluated at a single time point in the Health, Aging and Body Composition (Health ABC) study, so it was our view that the use of structural equations models would have been suboptimal. There are also a myriad of criticisms in the literature about the assumptions that must be met to assume causality when applying mediation analysis in any observational, longitudinal study—for example, no unmeasured confounding—which would be difficult to verify [4]. An initial step in a potential mediation analysis would be to explore the total effect of the exposure (initial vision) on mortality without considering possible mediators; these are the results we have presented. We went one step further to investigate if this relationship was modified by an initial performance-based measure of physical function. For example, re-expressing the HRs associated with the antagonistic interaction with stereoacuity (Table S5 [1]), we find the sub-additive interaction in that model indicates that the relationship between poor vision and mortality may be present only in those who have better mobility at baseline (aHR 1.35, 95% CI [1.18, 1.54] in those with SPPB ≥ 9; aHR 0.91, 95% CI [0.66, 1.24] in those with SPPB < 9; p = 0.02). There can be any number of intermediate factors that may further mediate this relationship, including changes in vision, treatment for visual impairment, changes in mobility, falls, and so forth. To fully understand the relationship between vision and mortality, it is our view that a more in-depth analysis would require the availability of considerable additional longitudinal data, consideration of initial effect modifiers, and moving beyond a single mediator model. Our observations utilizing the Health ABC study data are associations warranting further exploration, and are not intended as proof of causality. The antagonistic interaction between stereoacuity and poor mobility was not expected. Although we posit some explanations, whether this observation is reproducible in other appropriate datasets should be explored. In general, longitudinal measurements in large, diverse cohorts would be helpful in elucidating the complex relationship of changing vision and changing mobility over time with mortality and other outcomes. We agree that more severe visual impairment can be associated with greater risk of mortality, as has also been observed in the meta-analysis by Ehrlich et al. (2021) [5]. In the Health ABC study, we similarly observed, in comparison to those with visual acuity of 20/40 or better, that older adults with visual acuity worse than 20/60 had a higher adjusted hazard ratio for mortality (aHR 1.60, 95% CI [1.34, 1.90]) than those with visual acuity worse than 20/40 up to 20/60 (aHR 1.23, 95% CI [1.08, 1.39] see Table S6a [1]). As explained in the methods, Cox proportional hazards models were used to generate the hazards ratios in our study. Such models assume proportional hazards through time, but do not assume a constant hazard across time. While our Cox models explicitly model the hazard function over time, it is unclear to us what the authors mean by “time dimension…does not occur in the study design and analysis of the present study.” If this is referencing the lack of multiple measures of vision over time, we agree that this is a limitation of this study as well as prior studies. This underscores the need for longitudinal studies with repeated measures of vision. Our analysis was not designed to test for the effect of any vision or mobility intervention on mortality risk. Future studies should consider whether such interventions could be beneficial and the target population. Currently the literature is quite mixed on the impact of vision correction on falls, for example [6-12], and the effect may differ depending on the specific intervention or characteristics of the cohort including their co-morbid mobility status. As we noted, “whether interventions that address both poor vision and poor mobility can help improve survival should be studied in future work.” We agree that the Health ABC study by design intentionally enrolled individuals who were functionally healthier at baseline. However, we used data that started in the third year of the study, which is when vision was measured. In general, the cohort was not meant to be representative of the entire population. Rather, the study provides a unique opportunity to identify older adults who were initially quite functional and examined the role of initial vision on the hazard ratios for mortality. In the future, being able to identify older adults who are otherwise quite functional but may have subtle risk factors for adverse outcomes, such as mild visual impairment or mobility dysfunction, will be important when designing upstream interventions that can make a meaningful impact on their risk of disability and death. A.C.T. prepared the original draft of the letter. J.R., M.E.M., and S.B.K. reviewed and edited the letter. All authors approved the final version of the letter. The authors have nothing to report. The authors have nothing to report. The authors declare no conflicts of interest. Data sharing is not applicable as no new data was generated; the article describes existing research.
JAMAKritchevsky et al.Original Research
Observational studies highlight caloric restriction and senolytics may improve longevity in aging adults, suggesting new therapeutic strategies.
Blood AdvancesKlepin et al.Pilot Study
Interventions to maintain physical function during treatment may improve outcomes for older adults with acute myeloid leukemia (AML). We tested the feasibility of a randomized physical activity (PA) intervention among older adults (aged ≥60 years) receiving induction chemotherapy for newly diagnosed AML, and estimated the effect on physical function, quality of life (QOL), and symptoms. Intervention participants were offered PA sessions 5 days per week, tailored daily to symptoms during the induction hospitalization, along with weekly behavioral counseling sessions that continued monthly by phone for 6 months. The primary outcome was feasibility (recruitment, retention, and participation). The key secondary outcome of interest was the Short Physical Performance Battery (SPPB). SPPB score was assessed at baseline, weekly during hospitalization, and at 3 and 6 months. Among 96 eligible patients, 70 enrolled (mean age, 72.1 ± 6.3 years [range, 60-88]). Primary feasibility targets were met, with a recruitment rate of 72%, adherence of 74%, and average participation of 3 sessions per week. Among survivors, the retention rates were 96% and 95% at 3 (n = 51/53) and 6 (n = 42/44) months, respectively. In exploratory analyses, SPPB scores were maintained or improved in 38% of intervention participants vs 25% of controls at end of induction (n = 66; P = .21). There were no differences between groups in QOL or symptoms. A PA intervention with behavioral counseling during induction was feasible for older adults receiving intensive therapy for AML. This trial was registered at www.ClinicalTrials.gov as #NCT01519596.
Aperture NeuroLaurienti et al.Original Research
Cognitive and physical function are interrelated in aging. Co-occurring impairments in both domains can be debilitating and lead to increased risk of developing dementia. Amyloid beta (Aβ) deposition in the brain is linked to cognitive decline and is also associated with poorer physical function in older adults. However, significant inter-individual variability exists with respect to the influence of increased brain Aβ concentrations on cognitive and physical outcomes. Identifying factors that explain inter-individual variability in associations between Aβ and clinical outcomes could inform interventions designed to delay declines in both cognitive and physical function. Cognitive reserve (CR) is considered a buffer that allows for cognitive performance that is better than expected for a given level of brain injury or pathology. Although the neural mechanisms underlying CR remain unknown, there is growing evidence that resting-state brain networks may serve as a neural surrogate for CR. The current study utilized a statistical interaction model to evaluate if functional brain networks moderated associations between brain Aβ and cognitive and physical function in community-dwelling older adults from the Brain Networks and Mobility (B-NET) study. Significant moderations were found between Aβ levels and both the central executive and subcortical networks with cognitive and physical function. The findings suggest that brain networks serve as a buffer against the influence of Aβ accumulation on cognitive and physical function indicating that the network integrity could one of the neural mechanisms supporting CR.
The Journals of Gerontology Series AKarere et al.Cross-Sectional Study
BACKGROUND: Peak oxygen consumption during exercise (VO2peak), is a direct measure of cardiorespiratory fitness (CF), a key indicator of physical function and overall health. However, the molecular changes that underpin VO2peak variation are not clear. Our objective is to understand the microRNA (miRNA) signatures that relate to VO2peak variation, which could provide insights to novel mechanisms that contribute to low VO2peak. METHODS: We used small RNA sequencing to analyze baseline, cross-sectional serum samples from 72 participants (70- to 91-year old). We analyzed samples from individuals with low or high VO2peak (N = 18/group) as well as samples from 36 randomly selected participants spanning the entire spectrum of VO2peak. We used LIMMA analysis package for regression analysis and to identify differentially expressed miRNAs. RESULTS: We identified 1055 miRNAs expressed in all serum samples. Expression of 65 miRNAs differed between participants with low and high VO2peak (P < .05). After P-value adjustment, expression of 5 miRNAs (miR-1301-3p, -431-5p, -501-5p, -519a-3p, and -18a-3p) remained significantly different (FDR = 0.05). The Area Under the Curve for the five miRNAs ranged from 0.77 to 0.84. The optimal sensitivity and specificity ranged from 70% to 80% and 80% to 90%, respectively. After adjustment for age and sex covariates, 46 miRNAs significantly correlated with VO2peak (P < .05) and miR-519a-3p remained significant based on adjusted P-values. CONCLUSIONS: We identified a miRNA signature of VO2peak in older individuals that might provide insights to novel mechanisms that drive low VO2peak. Future studies will validate the findings in a larger, longitudinal study cohort.
Journal of Alzheimer s Disease ReportsHetrick et al.Original Research
Background: In healthy older adults (OA), the effects of amyloid-β (Aβ) deposition on cognitive functions involved in learning are unclear. Objective: This study aimed to determine how age, practice, and neuropsychological test performance are associated with performance change during the learning of three cognitive tasks, and if Aβ deposition impacts performance change in OA. Performance change was analyzed as change in accuracy and reaction time from the first to second and the first to third practice trials using linear mixed effect models. The basic model included age group and performance change, with neuropsychological test covariates. The second basic model mimicked the first but included Aβ deposition, instead of age group. Results: In the basic model, more practice resulted in a larger performance change for SGNT and SGRT, but not NBT. In the second basic model, after two NBT practice trials, performance change increased with greater amounts of Aβ deposition and worse information processing speed but, after three practice trials, decreased with greater amounts of Aβ deposition and worse information processing speed. Across the three tasks, greater Aβ deposition tended (non-significant trend) to be associated with smaller improvements after more practice. Conclusions: These results suggest that the ability to learn a cognitive task is maintained with age but is negatively impacted by Aβ deposition.
Molecular MetabolismAhn et al.Original Research
Cohort study reveals adipose tissue-secreted proteins linked to physical and cognitive decline in older adults, highlighting endocrine crosstalk across muscle and brain.
Current Developments in NutritionShea et al.Original Research
ABSTRACT As the global population of older adults increases, identifying strategies that modify biological aging has become an increasing priority for improving health span and lifespan. When coupled with the growing epidemic of overweight and obesity, nutritional strategies have garnered considerable research attention due to their potential to modulate both aging and metabolism at the cellular and molecular levels. Several key nutritional influences are currently being studied for their effects on aging biology, including caloric restriction, protein restriction, time-restricted eating, ketosis, and the gut microbiome. Of particular relevance is the role of dietary interventions in older adults with obesity, which must carefully balance the cardiometabolic benefits of weight loss with the unintended musculoskeletal losses, including muscle and bone mass. To discuss these critical issues, the Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop bringing together basic, clinical, and translational scientists in the fields of nutrition and aging biology. This meeting included sessions on calorie and protein restriction, timing of food intake, the gut microbiome, and obesity treatment for older adults. The agenda and recordings are archived at https://www.rccn-aging.org/nutrition-and-aging-biology. Here we describe the workshop's themes and discussions and highlight research gaps that, if filled, will considerably advance our understanding of the role of nutrition in healthy aging. Statement of Significance As the global population of older adults increases, identifying strategies that modify biological aging has become an increasing priority for improving health span and lifespan. When coupled with the growing epidemic of overweight and obesity, nutritional strategies have garnered considerable research attention due to their potential to modulate both aging and metabolism at the cellular and molecular levels. This article summarizes proceedings from a workshop on nutrition and the biology of aging and provides recommendations for future research to fill critical knowledge gaps.
Journal of the American Geriatrics SocietyThompson et al.Original Research
BACKGROUND: Older adults with visual impairment (VI) have a greater risk of mortality, but the reasons are poorly understood. We have shown that older adults with VI are more likely to have poor mobility performance on the short physical performance battery (SPPB). In this analysis, we examined whether VI predicted mortality over 10 years and if this was related to poor baseline mobility (SPPB < 9). METHODS: We analyzed 2457 older adults (mean age 75.6 (±2.8) years, 38.5% black, 51.9% female) who completed vision testing at the year 3 visit in the Health, Aging and Body Composition study. Cox proportional hazards models for mortality were right-censored at 10 years and adjusted for demographic and clinical comorbidities. VI (visual acuity < 20/40 or log contrast sensitivity < 1.55 or stereoacuity > 85) and SPPB < 9 were tested as main predictors and their interaction was tested. RESULTS: In separate multivariable models, VI (HR 1.511, 95% CI [1.335-1.709], p < 0.0001) and SPPB < 9 (HR 1.442, 95% CI [1.210-1.717], p < 0.0001) each predicted mortality. When including both poor mobility and vision variables as main effects, both poor mobility and impaired vision remained significant predictors of mortality in all models (all p < 0.001). When adding poor mobility (as a main effect and interaction with VI) and using unimpaired vision and mobility as the reference, those with only VI (HR 1.467, 95% CI [1.287-1.672], p < 0.0001) or only poor mobility (HR 1.380, 95% CI [0.963-1.979], p = 0.0792) had similar HRs, while those with both VI and poor mobility had an increased mortality risk (HR 2.035, 95% CI [1.643-2.522], p < 0.0001), but the interaction was not significant (p = 0.981). CONCLUSIONS: Older adults with both VI and poor mobility are at an additive increased risk of mortality. Future interventions may want to target older adults with both VI and poor mobility to improve survival.
GeroScienceMiller et al.Cohort Study
Using multiple sources, we provide the conceptual justification and statistical support for a multimorbidity outcome associated with obesity-related conditions, which we term the Health Conditions Index (HCI). This index was designed to capture the health effects of multi-year studies of caloric restriction for older adults with BMIs in the overweight or obesity classification. We used a subset of participants in the Health, Aging and Body Composition Cohort Study to evaluate multiple aspects of the index and its components over 5 years of follow-up. The 937 participants in the subset had an average age of 73 years and a BMI of 30.7 kg/m 2 ; 53% were female and 43% were Black; 80% were hypertensive and 14% had type 2 diabetes. Results demonstrated that the components of the index were consistently related to initial BMI and percent body fat on cohort entry, generally showed an increasing prevalence over the 5-year follow-up, and, as a composite index, exhibited an association between faster progression and higher initial levels of age, BMI, and percent body fat. Further, the initial HCI was associated with a statistically significant increase in the rate of mortality over 5 years of follow-up (hazard ratio = 1.22, 95% CI 1.04 to 1.44). By using outcomes like the HCI, clinical trials of caloric restriction in older adults may gain a better understanding of how intentional weight loss relates to future risk of multiple chronic conditions associated with aging.
Clinical Kidney JournalNeyra et al.Original Research
Background and hypothesis: Higher magnesium (Mg) intake is associated with a lower risk of stroke, heart failure and mortality, while there are limited data with kidney disease outcomes. We hypothesized that higher dietary Mg intake would be associated with a lower incidence of cardiovascular disease (CVD), chronic kidney disease (CKD) and kidney function decline. Methods: and at least 1 mL/min/year decline from baseline. Incident CVD was defined as incident coronary disease, heart failure, stroke or cardiovascular mortality. Multivariable Poisson regression and Cox proportional hazards models were used to evaluate the association of Mg intake with kidney and cardiovascular outcomes, respectively. Results: After excluding missing data, 2682 individuals were available for analysis. The median daily dietary Mg intake was 278 mg/day (11.4 mmol/day) (25th-75th percentile: 214-350 mg/day). Among 1871 individuals without baseline CKD, 522 developed incident CKD, while within the whole cohort, 394 (14.7%) had a ≥30% decline in eGFR over 10 years. Higher Mg intake was independently associated with lower risk of 30% eGFR decline [incidence rate ratio (IRR) per standard deviation (SD) higher Mg intake = 0.79 (95% confidence interval 0.66, 0.93)] and with a lower risk of incident CKD [IRR per SD higher Mg intake = 0.84 (95% confidence interval 0.73, 0.96)]. Among 1968 individuals without baseline CVD, 634 developed incident CVD. There was no association between Mg intake and overall incident CVD [adjusted hazard ratio 0.98 (95% confidence interval 0.85, 1.13)]. Conclusions: Higher Mg intake was associated with a lower risk of 30% decline in eGFR and incident CKD but not with incident CVD in a large cohort of older adults. The impact of Mg supplementation on kidney outcomes warrants further investigation.
