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1.
Nutrients ; 12(10)2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33036360

RESUMO

Resting metabolic rate (RMR) declines with aging and is related to changes in health status, but how specific health impairments impact basal metabolism over time has been largely unexplored. We analyzed the association of RMR with 15 common age-related chronic diseases for up to 13 years of follow-up in a population of 997 participants to the Baltimore Longitudinal Study of Aging. At each visit, participants underwent measurements of RMR by indirect calorimetry and body composition by DEXA. Linear regression models and linear mixed effect models were used to test cross-sectional and longitudinal associations of RMR and changes in disease status. Several diseases were associated with higher RMR at baseline. Independent of covariates, prevalent COPD and cancer, as well as incident diabetes, heart failure, and CKD were associated with a steeper decline in RMR over time. Chronic diseases seem to have a two-phase association with RMR. Initially, RMR may increase because of the high cost of resiliency homeostatic mechanisms. However, as the reserve capacity becomes exhausted, a catabolic cascade becomes unavoidable, resulting in loss of total and metabolically active mass and consequent RMR decline.

2.
Mech Ageing Dev ; 192: 111357, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32949594

RESUMO

There is a great deal of debate on the question of whether or not we know what ageing is (Ref. Cohen et al., 2020). Here, we consider what we believe to be the especially confused and confusing case of the ageing of the human immune system, commonly referred to as "immunosenescence". But what exactly is meant by this term? It has been used loosely in the literature, resulting in a certain degree of confusion as to its definition and implications. Here, we argue that only those differences in immune parameters between younger and older adults that are associated in some definitive manner with detrimental health outcomes and/or impaired survival prospects should be classed as indicators of immunosenescence in the strictest sense of the word, and that in humans we know remarkably little about their identity. Such biomarkers of immunosenescence may nonetheless indicate beneficial effects in other contexts, consistent with the notion of antagonistic pleiotropy. Identifying what could be true immunosenescence in this respect requires examining: (1) what appears to correlate with age, though generality across human populations is not yet confirmed; (2) what clearly is part of a suite of canonical changes in the immune system that happen with age; (3) which subset of those changes accelerates rather than slows aging; and (4) all changes, potentially population-specific, that accelerate agig. This remains an immense challenge. These questions acquire an added urgency in the current SARS-CoV-2 pandemic, given the clearly greater susceptibility of older adults to COVID-19.

3.
Free Radic Biol Med ; 160: 680-689, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32911084

RESUMO

BACKGROUND: Peripheral artery disease (PAD) is associated with mitochondrial dysfunction in calf skeletal muscle and a greater abundance of mitochondrial DNA (mtDNA) heteroplasmy. However, it is unknown whether calf skeletal muscle mtDNA of PAD participants harbors a greater abundance of mitochondrial DNA 4977-bp common deletion (mtDNA4977), strand breaks and oxidative damage (i.e., oxidized purines) compared to non-PAD participants and whether these mtDNA abnormalities are associated with poor walking performance in participants with PAD. METHODS: Calf muscle biopsies were obtained from 50 PAD participants (ankle-brachial index (ABI) < 0.95) and 25 non-PAD participants (ABI = 0.99-1.40) matched by age, sex, and race. The abundance of mtDNA copy number, mtDNA4977 deletion, strand breaks, and oxidized purines in selected mtDNA regions coding for electron transport chain (ETC) constituents and the non-coding D-Loop region was determined in calf muscle. All participants completed measurement of 6-min walk and usual and fast-paced 4-m walking velocity test. RESULTS: Participants with PAD (mean age = 65.4 years, SD = 6.9; 14 (28%) women, 38 (76%) black) and without PAD (mean age = 65.2 years, SD = 6.7; 7 (28%) women, 16 (64%) black) did not differ in the abundance of calf muscle mtDNA4977 deletion, mtDNA strand breaks, and oxidized purines. Though, a greater abundance of mtDNA strand breaks within ND4/5 genes was significantly associated with poorer 6-min walk distance, lower usual-paced 4-m walking velocity, and lower fast-paced 4-m walking velocity in non-PAD participants. Significant associations were also found in the density of strand break damage (i.e., damage per mtDNA copy) within ND1/2, ND4/5 and COII/ATPase 6/8 region with 6-min walk distance, usual-paced 4-m walking velocity and fast-paced 4-m walking velocity in non-PAD participants. Significant interactions were found between PAD presence vs. absence and density of strand break damage within ND1/2, ND4/5, COII/ATPase 6/8 regions for the associations with 6-min walk distance, usual-paced 4-m walking velocity, fast-paced 4-m walking velocity. Conversely, of the three walking performance measures only the usual-paced 4-m walking velocity showed a significant, although modest, negative association with the abundance of oxidized purines in the D-Loop (P = 0.031) and ND4/5 (P = 0.033) regions in the calf skeletal muscle of people with PAD. CONCLUSION: Overall, these data suggest that the abundance of calf muscle mtDNA strand breaks and mtDNA4977 common deletion are not associated with walking performance in people with PAD and may not be directly involved in the pathophysiology of PAD. Conversely, strand breaks in specific mtDNA regions may contribute to poor walking performance in people without PAD. Further study is needed to confirm whether usual-paced 4-m walking velocity is associated significantly with a greater abundance of oxidized purines in the D-loop, a "mutational hotspot" for oxidative damage, and why this association may differ from the association with 6-min walk distance and fast-paced 4-m walking velocity.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32941606

RESUMO

BACKGROUND: Multidimensional Prognostic Index (MPI) is recognized as prognostic tool in hospitalized patients, but data on the value of MPI in community-dwelling older persons are limited. Using data from a representative cohort of community-dwelling persons, we tested the hypothesis that MPI explains mortality, over 15 years of follow-up. METHODS: A standardized comprehensive geriatric assessment was used to calculate the MPI and to categorize participants in low-, moderate-, and high-risk classes. The results were reported as hazard ratios (HRs) and the accuracy was evaluated with the AUC (area under the curve), with 95% confidence intervals (CIs) and the C-index. We also reported the median survival time by standard age groups. RESULTS: All 1,453 participants (mean age 68.9 years, women=55.8%) enrolled in the InCHIANTI study at baseline were included. Compared to low risk group, participants in moderate (HR=2.10; 95%CI: 1.73-2.55) and high MPI risk group (HR=4.94; 95%CI: 3.91-6.24) had significantly higher mortality risk. The C-index of the model containing age, sex, and MPI was 82.1, indicating a very good accuracy of this model in explaining mortality. Additionally, the time-dependent AUC indicated that the accuracy of the model incorporating MPI to age and sex was excellent (>85.0) during the whole follow-up period. Compared to participants in the low-risk MPI group across different age-groups, those in medium- and high-risk groups survived 2.9 to 7.0 years less and 4.3 to 8.9 years less, respectively. CONCLUSIONS: In community-dwelling individuals, higher MPI values are associated with higher risk of all-cause mortality with a dose-response effect.

5.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120313831, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32938218

RESUMO

This brief review summarizes current evidence regarding lower extremity peripheral artery disease (PAD) and lower extremity skeletal muscle pathology. Lower extremity ischemia is associated with reduced calf skeletal muscle area and increased calf muscle fat infiltration and fibrosis on computed tomography or magnetic resonance imaging. Even within the same individual, the leg with more severe ischemia has more adverse calf muscle characteristics than the leg with less severe ischemia. More adverse computed tomography-measured calf muscle characteristics, such as reduced calf muscle density, are associated with higher rates of mobility loss in people with PAD. Calf muscle in people with PAD may also have reduced mitochondrial activity compared with those without PAD, although evidence is inconsistent. Muscle biopsy document increased oxidative stress in PAD. Reduced calf muscle perfusion, impaired mitochondrial activity, and smaller myofibers are associated with greater walking impairment in PAD. Preliminary evidence suggests that calf muscle pathology in PAD may be reversible. In a small uncontrolled trial, revascularization improved both the ankle-brachial index and mitochondrial activity, measured by calf muscle phosphocreatine recovery time. A pilot clinical trial showed that cocoa flavanols increased measures of myofiber health, mitochondrial activity, and capillary density while simultaneously improving 6-minute walk distance in PAD. Calf muscle pathological changes are associated with impaired walking performance in people with PAD, and interventions that both increase calf perfusion and improve calf muscle health are promising therapies to improve walking performance in PAD.

6.
Aging Cell ; : e13229, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32930491

RESUMO

Epigenetic clocks, developed using DNA methylation data, have been widely used to quantify biological aging in multiple tissues/cells. However, many existing epigenetic clocks are weakly correlated with each other, suggesting they may capture different biological processes. We utilize multi-omics data from diverse human tissue/cells to identify shared features across eleven existing epigenetic clocks. Despite the striking lack of overlap in CpGs, multi-omics analysis suggested five clocks (Horvath1, Horvath2, Levine, Hannum, and Lin) share transcriptional associations conserved across purified CD14+ monocytes and dorsolateral prefrontal cortex. The pathways enriched in the shared transcriptional association suggested links between epigenetic aging and metabolism, immunity, and autophagy. Results from in vitro experiments showed that two clocks (Levine and Lin) were accelerated in accordance with two hallmarks of aging-cellular senescence and mitochondrial dysfunction. Finally, using multi-tissue data to deconstruct the epigenetic clock signals, we developed a meta-clock that demonstrated improved prediction for mortality and robustly related to hallmarks of aging in vitro than single clocks.

7.
Neuroimage ; 223: 117289, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32835822

RESUMO

Investigation of relationships between age-related changes in regional brain volumes and changes in domain-specific cognition could provide insights into the neural underpinnings of individual differences in cognitive aging. Domain-specific cognition (memory, verbal fluency, visuospatial ability) and tests of executive function and attention (Trail-Making Test Part A and B) and 47 brain volumes of interest (VOIs) were assessed in 836 Baltimore Longitudinal Study of Aging participants with mean follow-up of 4.1 years (maximum 23.1 years). To examine the correlation between changes in domain-specific cognition and changes in brain volumes, we used bivariate linear mixed effects models with unstructured variance-covariance structure to estimate longitudinal trajectories for each variable of interest and correlations among the random effects of these measures. Higher annual rates of memory decline were associated with greater volume loss in 14 VOIs primarily within the temporal and occipital lobes. Verbal fluency decline was associated with greater ventricular enlargement and volume loss in 24 VOIs within the frontal, temporal, and parietal lobes. Decline in visuospatial ability was associated with volume loss in 3 temporal and parietal VOIs. Declines on the attentional test were associated with volume loss in 4 VOIs located within temporal and parietal lobes. Greater declines on the executive function test were associated with greater ventricular enlargement and volume loss in 10 frontal, parietal, and temporal VOIs. Our findings highlight domain-specific patterns of regional brain atrophy that may contribute to individual differences in cognitive aging.

8.
J Gerontol B Psychol Sci Soc Sci ; 75(8): e198-e203, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32835364

RESUMO

OBJECTIVES: Most studies of aging cognition have focused on risk factors for worse performance and on either genetic or environmental factors. In contrast, we examined whether 2 factors known to individually benefit aging cognition may interact to produce better cognition: environment-based positive age beliefs and the APOE ε2 gene. METHOD: The sample consisted of 3,895 Health and Retirement Study participants who were 60 years or older at baseline and completed as many as 5 assessments of cognition over 8 years. RESULTS: As predicted, positive age beliefs amplified the cognitive benefit of APOE ε2. In contrast, negative age beliefs suppressed the cognitive benefit of APOE ε2. We also found that positive age beliefs contributed nearly 15 times more than APOE ε2 to better cognition. DISCUSSION: This study provides the first known evidence that self-perceptions can influence the impact of a gene on cognition. The results underscore the importance of combined psychosocial and biological approaches to understanding cognitive function in older adults.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32766816

RESUMO

BACKGROUND: The operational definition of resilience is elusive and resilient people are difficult to identify. We used self-reported "major health event" (srMHE) to identify resilience and evaluate the functional and mortality trajectories associated with this condition. METHODS: We selected from the InCHIANTI study persons aged 65 or more who could perform the Short Physical Performance Battery at baseline and attended the three-years follow-up visit. We identified four groups: Controls:no srMHE and no decline in physical function; Decliners:no srMHE and decline in physical function; Resilient:srMHE and no decline in physical function; Non resilient:srMHE and decline in physical function. Linear mixed models and Cox regression were used to analyze changes in activities of daily living (ADL) score over 9 years and 10-years mortality across groups, respectively. RESULTS: The 313 participants that reported a srMHE had worse perceived health status and higher number of GP visits and prescribed drugs at baseline. Of these, 78 were Resilient and 235 Non resilient; of the remaining, 136 were Controls and 277 Decliners. Compared to the Controls, Resilient had similar change of ADL score over time (ß:-0.03,P:0.92) and mortality (HR:1.31, 0.76-2.23), while Decliners and Non resilient showed significantly higher mortality and, the latter, worsening of ADL score. Additional srMHE during follow-up affected the rate of change of ADL score and mortality more in the Controls group than in the Resilient group. CONCLUSIONS: A srMHE along with repeated evaluation of physical function may be used to identify resilience in older people, and may complement the standard functional evaluation of geriatric patients.

10.
Artigo em Inglês | MEDLINE | ID: mdl-32803242

RESUMO

BACKGROUND: Previous work has shown that poorer mitochondrial function is associated with age-related perceived fatigability. However, whether glucose oxidation and anaerobic metabolism are intermediate factors underlying this association remains unclear. METHODS: The total cross-sectional association between mitochondrial function and perceived fatigability was examined in 554 adults aged 22-99 years. Mitochondrial function was assessed by skeletal muscle oxidative capacity (kPCr) using 31P magnetic resonance spectroscopy. Perceived fatigability was measured by rating of perceived exertion after a 5-minute (0.67 m/s) treadmill walk. The intermediate role of glucose oxidation (measured by the rate of change of respiratory exchange ratio (RER change rate) during the 5-minute treadmill walk) and anaerobic metabolism (measured by ventilatory threshold (VeT) during a maximal treadmill test) was evaluated by examining their cross-sectional associations with kPCr and perceived exertion. RESULTS: For each 0.01/s lower kPCr, perceived fatigability was 0.47-point higher (p = 0.002). A 0.01/s lower kPCr was also associated with 8.3 L/min lower VeT (p < 0.001). Lower VeT was associated with higher fatigability at lower levels of kPCr but not at higher kPCr levels (ß for interaction = 0.017, p = 0.002). kPCr and RER change rate were not significantly associated (p = 0.341), but a 0.01/min higher RER change rate was associated with 0.12-point higher fatigability (p = 0.001). CONCLUSION: Poorer mitochondrial function potentially contributes to higher perceived fatigability through higher glucose oxidation and higher anaerobic metabolism. Future studies to further explore the longitudinal mechanisms between these metabolic changes and fatigability are warranted.

11.
JCI Insight ; 5(16)2020 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-32814718

RESUMO

Chronic inflammation is associated with physical frailty and functional decline in older adults; however, the molecular mechanisms of this linkage are not understood. A mouse model of chronic inflammation showed reduced motor function and partial denervation at the neuromuscular junction. Metabolomic profiling of these mice and further validation in frail human subjects showed significant dysregulation in the tryptophan degradation pathway, including decreased tryptophan and serotonin, and increased levels of some neurotoxic kynurenines. In humans, kynurenine strongly correlated with age, frailty status, TNF-αR1 and IL-6, weaker grip strength, and slower walking speed. To study the effects of elevated neurotoxic kynurenines on motor neuronal cell viability and axonal degeneration, we used motor neuronal cells treated with 3-hydroxykynurenine and quinolinic acid and observed neurite degeneration in a dose-dependent manner and potentiation of toxicity between 3-hydroxykynurenine and quinolinic acid. These results suggest that kynurenines mediate neuromuscular dysfunction associated with chronic inflammation and aging.

12.
Exp Gerontol ; 140: 111048, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32755612

RESUMO

OBJECTIVE: This study investigated associations of markers of oxidative stress and mitochondrial function in calf muscle biopsies with walking performance in people with and without lower extremity peripheral artery disease (PAD). METHODS: Participants with PAD (ankle-brachial index (ABI) <0.90) and without PAD (ABI: 0.90-1.50) underwent calf muscle biopsy and measurement of 6-min walk and four-meter walking velocity. PARP1 (Poly (ADP-Ribose) Polymerase 1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), silent information regulator 1 (SIRT1) and 4-hydroxynonenal (4HNE) expression were measured in calf muscle using western blot. RESULTS: Among 15 participants with PAD mean age: 66.8 years (standard deviation (SD): 6.4) and six without PAD (age: 64.4 years, SD: 5.9), mean PARP1-abundance in calf muscle was 1.16 ± 0.92 AU and 0.96 ± 0.38 AU, respectively (P = 0.61). Among participants with PAD after adjustment with ABI, a greater abundance of PARP1 was associated with poorer 6-min walking distance (r = -0.65, P = 0.01), usual-paced 4-m walking velocity (r = -0.73, P = 0.003) and slower fast-paced four-meter walking velocity (r = -0.51, P = 0.07). Among participants with PAD, ABI was not associated with PARP1 abundance in calf muscle (r = 0.02, P = 0.93). Among participants without PAD, skeletal muscle PARP1 abundance was not significantly associated with 6-min walk distance (r = -0.58; P = 0.22), usual-paced walking velocity (r = -0.26; P = 0.62), or fast-paced walking velocity (r = -0.21; P = 0.69), perhaps due to lack of statistical power. There were no associations of remaining calf muscle measures with walking performance. CONCLUSIONS: These findings are consistent with the hypothesis that calf skeletal muscle characteristics are related to walking performance, independently of severity of lower extremity arterial obstruction in people with PAD.

13.
Mech Ageing Dev ; 191: 111316, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32693105

RESUMO

At a recent symposium on aging biology, a debate was held as to whether or not we know what biological aging is. Most of the participants were struck not only by the lack of consensus on this core question, but also on many basic tenets of the field. Accordingly, we undertook a systematic survey of our 71 participants on key questions that were raised during the debate and symposium, eliciting 37 responses. The results confirmed the impression from the symposium: there is marked disagreement on the most fundamental questions in the field, and little consensus on anything other than the heterogeneous nature of aging processes. Areas of major disagreement included what participants viewed as the essence of aging, when it begins, whether aging is programmed or not, whether we currently have a good understanding of aging mechanisms, whether aging is or will be quantifiable, whether aging will be treatable, and whether many non-aging species exist. These disagreements lay bare the urgent need for a more unified and cross-disciplinary paradigm in the biology of aging that will clarify both areas of agreement and disagreement, allowing research to proceed more efficiently. We suggest directions to encourage the emergence of such a paradigm.

14.
Geroscience ; 42(5): 1377-1385, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32671621

RESUMO

A few studies report that parental longevity is associated with preserved cognition and physical function and lower risk of Alzheimer's disease. However, data on structural neuroimaging correlates of parental longevity and its spatial distribution are limited. This study aims to examine relationships of parental longevity with regional brain structure and to explore sex differences. We identified 12,970 UK Biobank participants (mean age = 64.4, 51.5%women) with data on parental longevity, regional gray matter volumes, and white matter microstructure. Participants were categorized based on whether at least one parent lived to age 85 or older or neither parent survived to age 85. Associations of parental longevity, maternal, and paternal longevity with each neuroimaging marker of interest were examined using linear regression, adjusted for demographics, APOE e4 status, lifestyle, and cardiometabolic conditions. Compared to participants whose both parents died before 85 (43%), those with at least one parent surviving to 85 (57%) had greater volumes in hippocampus, parahippocampal gyrus, middle temporal lobe, and primary sensorimotor cortex and had lower mean diffusivity in posterior thalamic radiation and uncinate fasciculus. Associations were prominent with maternal longevity. Adjustment for cardiometabolic conditions did not affect observed associations except mean diffusivity in posterior thalamic radiation. There were no structural differences in other areas. Parental longevity is associated with preserved brain structure localized in primary sensorimotor cortex and temporal areas including hippocampus. These relationships are prominent with maternal longevity. Longitudinal studies are needed to determine whether changes in these brain structures account for the association between parental longevity and dementia.

15.
Aging (Albany NY) ; 12(14): 14092-14124, 2020 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-32697766

RESUMO

DNA methylation has fundamental roles in gene programming and aging that may help predict mortality. However, no large-scale study has investigated whether site-specific DNA methylation predicts all-cause mortality. We used the Illumina-HumanMethylation450-BeadChip to identify blood DNA methylation sites associated with all-cause mortality for 12, 300 participants in 12 Cohorts of the Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium. Over an average 10-year follow-up, there were 2,561 deaths across the cohorts. Nine sites mapping to three intergenic and six gene-specific regions were associated with mortality (P < 9.3x10-7) independently of age and other mortality predictors. Six sites (cg14866069, cg23666362, cg20045320, cg07839457, cg07677157, cg09615688)-mapping respectively to BMPR1B, MIR1973, IFITM3, NLRC5, and two intergenic regions-were associated with reduced mortality risk. The remaining three sites (cg17086398, cg12619262, cg18424841)-mapping respectively to SERINC2, CHST12, and an intergenic region-were associated with increased mortality risk. DNA methylation at each site predicted 5%-15% of all deaths. We also assessed the causal association of those sites to age-related chronic diseases by using Mendelian randomization, identifying weak causal relationship between cg18424841 and cg09615688 with coronary heart disease. Of the nine sites, three (cg20045320, cg07839457, cg07677157) were associated with lower incidence of heart disease risk and two (cg20045320, cg07839457) with smoking and inflammation in prior CHARGE analyses. Methylation of cg20045320, cg07839457, and cg17086398 was associated with decreased expression of nearby genes (IFITM3, IRF, NLRC5, MT1, MT2, MARCKSL1) linked to immune responses and cardiometabolic diseases. These sites may serve as useful clinical tools for mortality risk assessment and preventative care.

16.
J Am Geriatr Soc ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32618359

RESUMO

BACKGROUND/OBJECTIVES: Anemia is a common condition in older adults for which fatigue, the primary symptom, often goes unrecognized as individuals typically equilibrate their activity to avoid fatigue. Whether assessing fatigability (i.e., susceptibility to fatigue) facilitates identification of anemia is unknown. This study examines the association between fatigability and prevalent, incident, and persistent subclinical and clinical anemia in well-functioning older adults. DESIGN, SETTING, PARTICIPANTS: Longitudinal analysis of 905 well-functioning men and women aged 60 to 89 years and followed for 1 to 5 years from the Baltimore Longitudinal Study of Aging conducted at the National Institute on Aging, Clinical Research Unit, Baltimore, MD. MEASUREMENTS: Perceived fatigability was assessed as a rating of perceived exertion (RPE) from 6 to 20 following a 5-minute treadmill walk at 1.5 mph (.67 m/s); fatigue was assessed as reported unusual tiredness in the past month. Clinical anemia was defined using World Health Organization hemoglobin cutpoints of below 13 g/dL and below 12 g/dL for men and women, respectively, and subclinical anemia was defined as 13.0 to 13.9 g/dL and 12.0 to 12.9 g/dL, respectively. RESULTS: Overall, 14% of participants had clinical and 30% had subclinical anemia at baseline. Each increment (1 RPE) of fatigability was associated after covariate adjustment with 14% (95% confidence interval [CI] = 5-25%, P = .005) and 8% (CI = 1-17%; P = .031), respectively, greater likelihood of prevalent clinical and subclinical anemia. An average of 2.2 years later, each 1 RPE increment in baseline fatigability predicted an 11% (CI = 2-20%; P = .016) higher likelihood of incident and/or persistent subclinical and clinical anemia. Reports of unusual tiredness were associated with prevalent subclinical anemia only. CONCLUSION: This study provides evidence that perceived fatigability may help identify well-functioning older adults with borderline to clinical anemia who are on a trajectory of persistently suboptimal or worsening hemoglobin status. Assessing fatigability may facilitate earlier diagnosis of health conditions that underlie persistent suboptimal hemoglobin status.

17.
J Gerontol A Biol Sci Med Sci ; 75(9): e95-e102, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32502253

RESUMO

BACKGROUND: Poor sleep may increase the likelihood of fatigue, and both are common in later life. However, prior studies of the sleep-fatigue relationship used subjective measures or were conducted in clinical populations; thus, the nature of this association in healthier community-dwelling older adults remains unclear. We studied the association of actigraphic sleep parameters with perceived fatigability-fatigue in response to a standardized task-and with conventional fatigue symptoms of low energy or tiredness. METHODS: We studied 382 cognitively normal participants in the Baltimore Longitudinal Study of Aging (aged 73.1 ± 10.3 years, 53.1% women) who completed 6.7 ± 0.9 days of wrist actigraphy and a perceived fatigability assessment, including rating of perceived exertion (RPE) after a 5-minute treadmill walk or the Pittsburgh Fatigability Scale (PFS). Participants also reported non-standardized symptoms of fatigue. RESULTS: After adjustment for age, sex, race, height, weight, comorbidity index, and depressive symptoms, shorter total sleep time (TST; <6.3 hours vs intermediate TST ≥6.3 to 7.2 hours) was associated with high RPE fatigability (odds ratio [OR] = 2.56, 95% confidence interval [CI] = 1.29, 5.06, p = .007), high PFS physical (OR = 1.88, 95% CI = 1.04, 3.38, p = .035), and high mental fatigability (OR = 2.15, 95% CI = 1.02, 4.50, p = .044), whereas longer TST was also associated with high mental fatigability (OR = 2.19, 95% CI = 1.02, 4.71, p = .043). Additionally, longer wake bout length was associated with high RPE fatigability (OR = 1.53, 95% CI = 1.14, 2.07, p = .005), and greater wake after sleep onset was associated with high mental fatigability (OR = 1.14, 95% CI = 1.01, 1.28, p = .036). CONCLUSION: Among well-functioning older adults, abnormal sleep duration and sleep fragmentation are associated with greater perceived fatigability.

18.
19.
Neurobiol Aging ; 94: 81-88, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32593031

RESUMO

A high hippocampal volume polygenic predictor score (HV-PPS), computed based on GWAS summary statistics (n = 33,536), could be protective against declines in brain volume and cognition in older adults. Linear mixed-effects models with random intercepts and slopes were used to estimate associations of HV-PPS with baseline and annual rate of change in both brain volumes (n = 508) and cognitive performance (n = 1041) in Caucasian Baltimore Longitudinal Study of Aging participants. Higher HV-PPS was associated with greater baseline volumes of the hippocampus and parahippocampal gyrus, and slower rates of ventricular enlargement and volume loss in frontal and parietal white matter, all adjusted for intracranial volume. In addition, higher HV-PPS was associated with better executive function performance and slower rates of decline in verbal fluency scores over time. Individuals with a genetic predisposition toward larger hippocampal volumes show better baseline executive function, slower decline in verbal fluency performance, and slower rates of longitudinal brain atrophy.

20.
Geroscience ; 42(4): 1175-1182, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32572752

RESUMO

Although a persistent inflammatory state has long been associated with aging and negative health outcomes, the underlying mechanisms remain unclear. Mitochondrial dysfunction has been proposed as a cause of inflammaging, but evidence of an association in humans is lacking. In this study, we analyzed the cross-sectional association between inflammatory biomarkers and mitochondrial oxidative capacity in skeletal muscle, assessed as post-exercise phosphocreatine recovery time constant by phosphorus magnetic resonance spectroscopy, in a population of 669 adults (mean age 67 years) from the Baltimore Longitudinal Study of Aging. We observed that participants with lower mitochondrial oxidative capacity exhibited hallmarks of inflammation, specifically markedly higher levels of interleukin-6 and C-reactive protein, as well as increased erythrocyte sedimentation rate when compared with participants with better oxidative capacity, independent of age and sex. We speculate that this association reflects the observation that products of damaged mitochondria, such as mitochondrial DNA, activate multiple pathways that lead to inflammation. Furthermore, excess production of oxidative species (ROS) by dysfunctional mitochondria could trigger inflammation either directly via NF-κB or through oxidative damage to proteins, lipids, and nucleic acids. Longitudinal studies are necessary to ascertain whether and through which mechanisms mitochondrial dysfunction activate inflammation or whether both these phenomena derive from a common root.

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