Journals of Gerontology Series A-Biological Sciences and Medical Sciences最新文献

Biological mechanisms that lead to multimorbidity are mostly unknown, and metabolomic profiles are promising to explain different pathways in the aging process. The aim of this study was to assess the prospective association between plasma fatty acids and other lipids, and multimorbidity in older adults. Data were obtained from the Spanish Seniors-ENRICA 2 cohort, comprising noninstitutionalized adults ≥65 years old. Blood samples were obtained at baseline and after a 2-year follow-up period for a total of 1 488 subjects. Morbidity was also collected at baseline and end of the follow-up from electronic health records. Multimorbidity was defined as a quantitative score, after weighting morbidities (from a list of 60 mutually exclusive chronic conditions) by their regression coefficients on physical functioning. Generalized estimating equation models were employed to assess the longitudinal association between fatty acids and other lipids, and multimorbidity, and stratified analyses by diet quality, measured with the Alternative Healthy Eating Index-2010, were also conducted. Among study participants, higher concentrations of omega-6 fatty acids [coef. per 1-SD increase (95% CI) = -0.76 (-1.23, -0.30)], phosphoglycerides [-1.26 (-1.77, -0.74)], total cholines [-1.48 (-1.99, -0.96)], phosphatidylcholines [-1.23 (-1.74, -0.71)], and sphingomyelins [-1.65 (-2.12, -1.18)], were associated with lower multimorbidity scores. The strongest associations were observed for those with a higher diet quality. Higher plasma concentrations of omega-6 fatty acids, phosphoglycerides, total cholines, phosphatidylcholines, and sphingomyelins were prospectively associated with lower multimorbidity in older adults, although diet quality could modulate the associations found. These lipids may serve as risk markers for multimorbidity.

Adequate sleep is essential for healthy physical, emotional, and cognitive functioning, including memory. However, sleep ability worsens with increasing age. Older adults on average have shorter sleep durations and more disrupted sleep compared with younger adults. Age-related sleep changes are thought to contribute to age-related deficits in episodic memory. Nonetheless, the nature of the relationship between sleep and episodic memory deficits in older adults is still unclear. Further complicating this relationship are age-related changes in circadian rhythms such as the shift in chronotype toward morningness and decreased circadian stability, which may influence memory abilities as well. Most sleep and cognitive aging studies do not account for circadian factors, making it unclear whether age-related and sleep-related episodic memory deficits are partly driven by interactions with circadian rhythms. This review will focus on age-related changes in sleep and circadian rhythms and evidence that these factors interact to affect episodic memory, specifically encoding and retrieval. Open questions, methodological considerations, and clinical implications for diagnosis and monitoring of age-related memory impairments are discussed.

Background: Adverse childhood experiences (ACEs) are associated with sleep impairment across the life span, but little is known about modifiable factors that may ameliorate this relationship, such as adaptive emotion regulation (ER) skills.

Methods: Data were obtained from an online questionnaire completed by a community sample of older adults (N = 278). The questionnaire included the Pittsburgh Sleep Quality Index, an Adverse Childhood Experiences questionnaire, the Cognitive Emotion Regulation Questionnaire (CERQ), and measures of health conditions, and other sample demographics. Moderation analyses were used to examine the interaction between ACEs and 5 adaptive ER skills of CERQ on sleep quality in older adults, while accounting for the effects of age, sex, income, body mass index, and health.

Results: ACEs were significantly associated with worse sleep quality in older adults, and this effect was moderated by positive reappraisal and refocusing on planning (all ps < .05). For individuals reporting greater use of these ER skills, ACEs had no effect on sleep quality, whereas for individuals reporting less frequent use of these ER skills, ACEs were associated with substantially worse sleep quality. This relationship remained significant after accounting for age, sex, income, body mass index, and health conditions in the model.

Conclusions: The effects of ACEs on sleep quality persist into older age; however, greater use of ER skills that focus on positively reframing negative events and identifying strategies for coping protect against sleep impairment in individuals with higher ACEs.

Aging is believed to induce insulin resistance in humans. However, when and how insulin sensitivity changes with aging remains unclear in both humans and mice. In this study, groups of male C57BL/6N mice at 9-19 weeks (young), 34-67 weeks (mature adult), 84-85 weeks (presenile), and 107-121 weeks of age underwent hyperinsulinemic-euglycemic clamp studies with somatostatin infusion under awake and nonrestrained conditions. The glucose infusion rates for maintaining euglycemia were 18.4 ± 2.9, 5.9 ± 1.3, 20.3 ± 7.2, and 25.3 ± 4.4 mg/kg/min in young, mature adult, presenile, and aged mice, respectively. Thus, compared with young mice, mature adult mice exhibited the expected insulin resistance. In contrast, presenile and aged mice showed significantly higher insulin sensitivity than mature adult mice. These age-related changes were mainly observed in glucose uptake into adipose tissue and skeletal muscle (rates of glucose disappearance were 24.3 ± 2.0, 17.1 ± 1.0, 25.5 ± 5.2, and 31.8 ± 2.9 mg/kg/min in young, mature adult, presenile, and aged mice, respectively). Epididymal fat weight and hepatic triglyceride levels were higher in mature adult mice than those in young and aged mice. Our observations indicate that, in male C57BL/6N mice, insulin resistance appears at the mature adult stage of life but subsequently improves markedly. These alterations in insulin sensitivity are attributable to changes in visceral fat accumulations and age-related factors.

Fat-free mass (FFM) is a heterogeneous compartment comprising body cell mass (BCM), intracellular water (ICW), extracellular solids, and extracellular water (ECW). The BCM/FFM and ECW/ICW ratios vary among individuals and decrease with age. This study aimed to determine whether BCM/FFM and ECW/ICW ratios are predictors of maximal oxygen uptake (V̇̇O2peak) independently of age, sex, and objectively measured physical activity (PA). A total of 115 Japanese males and females, aged 55.3 ± 8.0 years (mean ± standard deviation), were included in the study. Anthropometry, explosive leg muscle power, and V̇̇O2peak were measured, and BCM, FFM, ICW, and ECW were estimated. Step count and PA were objectively measured using a triaxial accelerometer. Blood flow volume was assessed using ultrasonography. BCM and ICW were negatively correlated with age, whereas FFM and ECW were not significantly correlated with age. FFM, ICW/ECW, BCM/FFM, step counts, moderate and vigorous PA, and leg muscle power were positively correlated with V̇̇O2peak, even after adjusting for age and sex (p < .05). Multiple regression analysis indicated that either BCM/FFM or ECW/ICW, leg power, and objectively measured PA were associated with V̇̇O2peak independent of age, sex, and FFM. Blood flow volume was significantly correlated with ECW (p < .05), but not with BCM. The BCM/FFM and ECW/ICW ratios were significant predictors of V̇̇O2peak, independent of age, sex, FFM, leg power, and objectively measured PA.

Chronic activation of inflammatory pathways (CI) and mitochondrial dysfunction are independently linked to age-related functional decline and early mortality. Interleukin 6 (IL-6) is among the most consistently elevated chronic activation of inflammatory pathways markers, but whether IL-6 plays a causative role in this mitochondrial dysfunction and physical deterioration remains unclear. To characterize the role of IL-6 in age-related mitochondrial dysregulation and physical decline, we have developed an inducible human IL-6 (hIL-6) knock-in mouse (TetO-hIL-6mitoQC) that also contains a mitochondrial-quality control reporter. Six weeks of hIL-6 induction resulted in upregulation of proinflammatory markers, cell proliferation and metabolic pathways, and dysregulated energy utilization. Decreased grip strength, increased falls off the treadmill, and increased frailty index were also observed. Further characterization of skeletal muscles postinduction revealed an increase in mitophagy, downregulation of mitochondrial biogenesis genes, and an overall decrease in total mitochondrial numbers. This study highlights the contribution of IL-6 to mitochondrial dysregulation and supports a causal role of hIL-6 in physical decline and frailty.

The aging process is complicated and involves diverse organ dysfunction; furthermore, the biomarkers that are able to reflect biological aging are eagerly sought after to monitor the system-wide decline associated with the aging process. To address this, we performed a metabolomics analysis using a longitudinal cohort study from Taiwan (N = 710) and established plasma metabolomic age using a machine learning algorithm. The resulting estimation of age acceleration among the older adults was found to be correlated with HOMA-insulin resistance. In addition, a sliding window analysis was used to investigate the undulating decrease in hexanoic and heptanoic acids that occurs among the older adults at different ages. A comparison of the metabolomic alterations associated with aging between humans and mice implied that ω-oxidation of medium-chain fatty acids was commonly dysregulated in older subjects. Among these fatty acids, sebacic acid, an ω-oxidation product produced by the liver, was significantly decreased in the plasma of both older humans and aged mice. Notably, an increase in the production and consumption of sebacic acid within the liver tissue of aged mice was observed, along with an elevation of pyruvate-to-lactate conversion. Taken together, our study reveals that sebacic acid and metabolites of ω-oxidation are the common aging biomarkers in both humans and mice. The further analysis suggests that sebacic acid may play an energetic role in supporting the production of acetyl-CoA during liver aging, and thus its alteration in plasma concentration potentially reflects the aging process.

Background: Evidence on sleep duration or quality and cognitive function in diverse older adults is limited. We examined prospective associations between subjective sleep measures and cognitive function, with modifying effects of sex and age (<65 vs ≥65 years).

Methods: Data are from the longitudinal Boston Puerto Rican Health Study, Waves 2 (n = 943) and 4 (n = 444), with mean follow-up of 10.5 years (range 7.2-12.8). Subjective measures of sleep duration (short <7, ref. 7, or long ≥8 hours) and insomnia symptoms (sum of difficulty falling asleep, waking up at night, and early morning awakening), were assessed at Wave 2. Linear regression models were used to assess changes in global cognition, executive function, memory, and Mini-Mental State Examination, and tested for modifying roles of sex and age.

Results: Significant 3-way interaction (sex × age × cognition) in fully adjusted models showed greater decline in global cognitive function in older men with short (β [95% confidence interval]: -0.67 [-1.24, -0.10]) or long sleep duration (-0.92 [-1.55, -0.30]), compared to women, younger men, and older men with 7 hours of sleep. Insomnia symptoms were associated with a greater decline in memory (-0.54, [-0.85, -0.22]) among older men, compared to women and younger men.

Conclusion: Sleep duration showed a U-shaped association with cognitive decline, and insomnia symptoms were associated with memory decline in fully adjusted models. Older men, versus women and younger men, were at relatively greater risk for cognitive decline associated with sleep factors. These findings are important for personalizing sleep interventions to support cognitive health.

Annual fishes of the genus Nothobranchius have been widely used in cognitive, behavioral, and genetic studies, and have become an excellent animal model for studying aging. However, the development and degeneration of immune organs in annual fishes and the antagonistic effects of resveratrol remain unclear. In the present study, the development of thymus and kidney was investigated systematically using Nothobranchius guentheri from larvae, juveniles, and young and old fish with hematoxylin and eosin staining. We found that thymus primordium was observed first in the larvae at 2 days after hatching (dah). After the lymphoid cells became evident at 5 dah, the thymus acquired an irregular shape at 7 dah. Then it formed a wedge shape at 15 dah. Thymus looked as homogeneous distribution of lymphocytes at 1 month old, and it differentiated into cortex and medulla approximately in 2-month-old fish. Combined with TUNEL and senescence-associated β-galactosidase (SA-β-gal) staining, it showed the degeneration of the thymus appeared in 4-month-old fish. Kidney primordium appeared on 1 dah, and the glomerulus was visible at 7 dah. The nephrogenic activity was most apparent in 1-month-old fish. A large hematopoietic tissue was arranged in the renal interstitium in 2- and 3-month-old fish. In 6-month-old fish, the kidney structure became less dense. By 12 months, the kidney exhibited the most pronounced histological characteristics of aging. Feeding resveratrol ameliorated renal fibrosis and SA-β-gal staining with age, increased SIRT1 and SIRT3 expression, and decreased the levels of NF-κB and inflammatory factors in thymus and kidney of the fish. We provided basic data for the development and degeneration of immune organs and resveratrol's anti-aging effects in short-lived fish.

Background: Understanding fall circumstances can help researchers better identify causes of falls and develop effective and tailored fall prevention programs. This study aims to describe fall circumstances among older adults from quantitative data using conventional statistical approaches and qualitative analyses using a machine learning approach.

Methods: The MOBILIZE Boston Study enrolled 765 community-dwelling adults aged 70 years and older in Boston, MA. Occurrence and circumstances of falls (ie, locations, activities, and self-reported causes of falls) were recorded using monthly fall calendar postcards and fall follow-up interviews with open- and close-ended questions during a 4-year period. Descriptive analyses were used to summarize circumstances of falls. Natural language processing was used to analyze narrative responses from open-ended questions.

Results: During the 4-year follow-up, 490 participants (64%) had at least 1 fall. Among 1 829 falls, 965 falls occurred indoors and 804 falls occurred outdoors. Commonly reported activities when the fall occurred were walking (915, 50.0%), standing (175, 9.6%), and going down stairs (125, 6.8%). The most commonly reported causes of falls were slip or trip (943, 51.6%) and inappropriate footwear (444, 24.3%). Using qualitative data, we extracted more detailed information on locations and activities, and additional information on obstacles related to falls and commonly reported scenarios such as "lost my balance and fell."

Conclusions: Self-reported fall circumstances provide important information on both intrinsic and extrinsic factors contributing to falls. Future studies are warranted to replicate our findings and optimize approaches to analyzing narrative data on fall circumstances in older adults.