Abstract Bradykinesia is the most important feature contributing to motor difficulties in Parkinson’s disease (PD). However, the pathophysiology underlying bradykinesia is not fully understood. One ...important aspect is that PD patients have difficulty in performing learned motor skills automatically, but this problem has been generally overlooked. Here we review motor automaticity associated motor deficits in PD, such as reduced arm swing, decreased stride length, freezing of gait, micrographia and reduced facial expression. Recent neuroimaging studies have revealed some neural mechanisms underlying impaired motor automaticity in PD, including less efficient neural coding of movement, failure to shift automated motor skills to the sensorimotor striatum, instability of the automatic mode within the striatum, and use of attentional control and/or compensatory efforts to execute movements usually performed automatically in healthy people. PD patients lose previously acquired automatic skills due to their impaired sensorimotor striatum, and have difficulty in acquiring new automatic skills or restoring lost motor skills. More investigations on the pathophysiology of motor automaticity, the effect of L-dopa or surgical treatments on automaticity, and the potential role of using measures of automaticity in early diagnosis of PD would be valuable.
Declines in both physical and cognitive function are associated with increasing age. Understanding the physiological link between physical frailty and cognitive decline may allow us to develop ...interventions that prevent and treat both conditions. Although there is significant epidemiological evidence linking physical frailty to cognitive decline, a complete understanding of the underpinning biological basis of the two disorders remains fragmented. This narrative review discusses insights into the potential roles of chronic inflammation, impaired hypothalamic-pituitary axis stress response, imbalanced energy metabolism, mitochondrial dysfunction, oxidative stress, and neuroendocrine dysfunction linking physical frailty with cognitive decline. We highlight the importance of easier identification of strategic approaches delaying the progression and onset of physical frailty and cognitive decline as well as preventing disability in the older population.
Our understanding of how aging affects the cellular and molecular components of the vasculature and contributes to cardiovascular diseases is still limited. Here we report a single-cell ...transcriptomic survey of aortas and coronary arteries in young and old cynomolgus monkeys. Our data define the molecular signatures of specialized arteries and identify eight markers discriminating aortic and coronary vasculatures. Gene network analyses characterize transcriptional landmarks that regulate vascular senility and position FOXO3A, a longevity-associated transcription factor, as a master regulator gene that is downregulated in six subtypes of monkey vascular cells during aging. Targeted inactivation of FOXO3A in human vascular endothelial cells recapitulates the major phenotypic defects observed in aged monkey arteries, verifying FOXO3A loss as a key driver for arterial endothelial aging. Our study provides a critical resource for understanding the principles underlying primate arterial aging and contributes important clues to future treatment of age-associated vascular disorders.
Background/Objectives
Frailty in older adults predicts dependence and mortality and is a major challenge for healthcare systems in countries with rapidly aging populations. Little is known about ...frailty in China. We investigated the prevalence and associated risk factors of frailty in older adults in China.
Design
Cross‐sectional.
Setting
Data were obtained from the China Comprehensive Geriatric Assessment Study, conducted in 2011–12, which was the first uniform comprehensive assessment system adopted in China.
Participants
Older adults from 7 cities were selected based on well‐established cluster, stratification, and random selection statistical sampling techniques (N = 5,844).
Measurements
The Comprehensive Geriatric Assessment‐Frailty Index was measured based on demographic characteristics, physical health, physical function, living behavior and social function, mental health, and cognitive function.
Results
The overall weighted prevalence of frailty was 9.9%: 12.7% in southwestern China, 11.0% in northern China, 5.9% in northwestern China, 5.0% in south‐central China, 2.5% in eastern China, and 2.3% in northeastern China. The prevalence of frailty increased with age and was significantly higher in women and those living in rural areas. After adjusting for sex, age, area, region, and education, activity of daily living impairment was the strongest risk factor for frailty. Chronic diseases, depression, poor lifestyle, and geriatric syndromes were also independent risk factors.
Conclusion
Our study provides epidemiological characteristics and the risk factors of frailty in China; the findings indicate greater regional disparities. Efforts to promote physical, psychological, and social health in older adults are a core objective of health policy, especially in women and those living in rural areas.
Aging is a major risk factor for many diseases, especially in highly prevalent cardiopulmonary comorbidities and infectious diseases including Coronavirus Disease 2019 (COVID-19). Resolving cellular ...and molecular mechanisms associated with aging in higher mammals is therefore urgently needed. Here, we created young and old non-human primate single-nucleus/cell transcriptomic atlases of lung, heart and artery, the top tissues targeted by SARS-CoV-2. Analysis of cell type-specific aging-associated transcriptional changes revealed increased systemic inflammation and compromised virus defense as a hallmark of cardiopulmonary aging. With age, expression of the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) was increased in the pulmonary alveolar epithelial barrier, cardiomyocytes, and vascular endothelial cells. We found that interleukin 7 (IL7) accumulated in aged cardiopulmonary tissues and induced ACE2 expression in human vascular endothelial cells in an NF-κB-dependent manner. Furthermore, treatment with vitamin C blocked IL7-induced ACE2 expression. Altogether, our findings depict the first transcriptomic atlas of the aged primate cardiopulmonary system and provide vital insights into age-linked susceptibility to SARS-CoV-2, suggesting that geroprotective strategies may reduce COVID-19 severity in the elderly.
To develop Clinical Practice Guidelines for the screening, assessment and management of the geriatric condition of frailty.
An adapted Grading of Recommendations, Assessment, Development, and ...Evaluation approach was used to develop the guidelines. This process involved detailed evaluation of the current scientific evidence paired with expert panel interpretation. Three categories of Clinical Practice Guidelines recommendations were developed: strong, conditional, and no recommendation.
Strong recommendations were (1) use a validated measurement tool to identify frailty; (2) prescribe physical activity with a resistance training component; and (3) address polypharmacy by reducing or deprescribing any inappropriate/superfluous medications. Conditional recommendations were (1) screen for, and address modifiable causes of fatigue; (2) for persons exhibiting unintentional weight loss, screen for reversible causes and consider food fortification and protein/caloric supplementation; and (3) prescribe vitamin D for individuals deficient in vitamin D. No recommendation was given regarding the provision of a patient support and education plan.
The recommendations provided herein are intended for use by healthcare providers in their management of older adults with frailty in the Asia Pacific region. It is proposed that regional guideline support committees be formed to help provide regular updates to these evidence-based guidelines.
Accumulating evidence indicates an association between the circadian clock and the aging process. However, it remains elusive whether the deregulation of circadian clock proteins underlies stem cell ...aging and whether they are targetable for the alleviation of aging-associated syndromes. Here, we identified a transcription factor-independent role of CLOCK, a core component of the molecular circadian clock machinery, in counteracting human mesenchymal stem cell (hMSC) decay. CLOCK expression was decreased during hMSC aging. In addition, CLOCK deficiency accelerated hMSC senescence, whereas the overexpression of CLOCK, even as a transcriptionally inactive form, rejuvenated physiologically and pathologically aged hMSCs. Mechanistic studies revealed that CLOCK formed complexes with nuclear lamina proteins and KAP1, thus maintaining heterochromatin architecture and stabilizing repetitive genomic sequences. Finally, gene therapy with lentiviral vectors encoding CLOCK promoted cartilage regeneration and attenuated age-related articular degeneration in mice. These findings demonstrate a noncanonical role of CLOCK in stabilizing heterochromatin, promoting tissue regeneration, and mitigating aging-associated chronic diseases.
Molecular mechanisms of ovarian aging and female age-related fertility decline remain unclear. We surveyed the single-cell transcriptomic landscape of ovaries from young and aged non-human primates ...(NHPs) and identified seven ovarian cell types with distinct gene-expression signatures, including oocyte and six types of ovarian somatic cells. In-depth dissection of gene-expression dynamics of oocytes revealed four subtypes at sequential and stepwise developmental stages. Further analysis of cell-type-specific aging-associated transcriptional changes uncovered the disturbance of antioxidant signaling specific to early-stage oocytes and granulosa cells, indicative of oxidative damage as a crucial factor in ovarian functional decline with age. Additionally, inactivated antioxidative pathways, increased reactive oxygen species, and apoptosis were observed in granulosa cells from aged women. This study provides a comprehensive understanding of the cell-type-specific mechanisms underlying primate ovarian aging at single-cell resolution, revealing new diagnostic biomarkers and potential therapeutic targets for age-related human ovarian disorders.
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•Single-cell transcriptomic roadmap of NHP ovarian aging•Molecular signatures revealed for NHP oocytes at stepwise developmental stages•Cell-type-specific inactivation of antioxidant genes in aged monkey and human ovaries
Single-cell transcriptomic analysis in ovaries of young and old cynomolgus monkeys identifies aging-associated and cell-type-specific dysregulation of antioxidative pathways.
Aim
Obesity is found to be associated with frailty. Body mass index (BMI) and waist circumference (WC) are the commonly used measures for obesity, the former is more closely related to general ...obesity and body weight; the latter can more accurately reflect abdominal obesity and is more closely associated with metabolic disorders. In this study, we intend to study the relationship between frailty, BMI and WC among older people.
Methods
Data were derived from the Beijing Longitudinal Study on Aging II Cohort, which included 6320 people 65 years or older from three urban districts in Beijing. A Frailty Index derived from 33 items was developed according to Rockwood’s cumulative deficits method. A Frailty Index ≥ 0.25 was used as the cut-off criteria. BMI was classified as underweight, normal, overweight, or obese (< 18.5, 18.5–< 24.0, 24.0–27.9, ≥ 28.0 kg/m
2
, respectively). High WC was defined as WC ≥ 85 cm in men and ≥ 80 cm in women.
Results
People with a larger BMI (≥ 28.0 kg/m
2
, 22.6%) or a larger WC (18.5%) were more likely to be frail. People with normal BMI and overweight people do not suffer from higher prevalence for frailty. In comparison with individuals with normal BMI (18.5–< 24.0 kg/m
2
) and normal WC (< 85 cm in men, <80 cm in women), the risk of frailty was higher among individuals who have normal BMI and large WC (odds ratio 1.68; 95% CI 1.33–2.12), have overweight and large WC (odds ratio 1.58; 95% CI 1.23–1.96), or have obesity and large WC (odds ratio 2.28; 95% CI 1.79–2.89). In people with normal WC, only those who are underweight have a higher risk for frailty (odds ratio 1.65, 95% CI 1.08–2.52). In comparison with BMI, the relation of WC with the risk for frailty was much closer.
Conclusions
Abdominal obesity is more closely associated with incidence of frailty than general obesity in the elderly. Older adults with large waist circumference are more likely to be frail. Frailty in the elderly might be more closely related to metabolic disorders. WC might be a better measurement to detect frailty than BMI, given its relationship with metabolic disorders.
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