Current translational geriatrics and experimental gerontology reports最新文献

As life expectancy in the United States continues to increase, the maintenance of physical independence among older Americans has emerged as a major clinical and public health priority. Therefore, there is an urgent need to identify interventions that can maintain or enhance cognitive and physical function with the goal of preventing or delaying the onset of disability. To date, caloric restriction (CR) is the only method that has been consistently found to increase lifespan and delay the onset of age-associated diseases such as cancer and diabetes across multiple species. The promise of calorie restriction as an intervention to improve health and/or maintain function in humans, however, only holds if individuals are able to adhere to this intervention over the long-term. Unfortunately, long-term adherence to CR regimens is notoriously poor likely due to complex interactions between behavioral, physiological, psychological, and environmental variables. Thus, a current challenge for both researchers and clinicians is to identify methods that can assist individuals in maintaining CR over the long-term.

Interventions to improve walking in older adults have historically been multifactorial (i.e. strengthening, endurance and flexibility programs) focusing on improving the underlying impairments. These impairment-based programs have resulted in only modest improvements in walking. In older adults, walking is slow, less stable, inefficient, and the timing and coordination of stepping with postures and phases of gait is poor. We argue the timing and coordination problems are evidence of the loss of motor skill in walking. Taking a lesson from the sports world and from neurorehabilitation, task-oriented motor learning exercise is an essential component of training to improve motor skill and may be a beneficial approach to improving walking in older adults. In this article we: 1) briefly review the current literature regarding impairment-based interventions for improving mobility, 2) discuss why the results have been only modest, and 3) suggest an alternative approach to intervention (i.e. task oriented motor learning).

Cardiac senescence and age-related disease development have gained general attention and recognition in the past decades due to increased accessibility and quality of health care. The advancement in global civilization is complementary to concerns regarding population aging and development of chronic degenerative diseases. Cardiac degeneration has been rigorously studied. The molecular mechanisms of cardiac senescence are on multiple cellular levels and hold a multilayer complexity level, thereby hampering development of unambiguous treatment protocols. In particular, the synergistic exchange of the senescence phenotype through a senescence secretome between myocytes and stem cells appears complicated and is of great future therapeutic value. The current review article will highlight hallmarks of senescence, cardiac myocyte and stem cell senescence, and the mutual exchange of senescent secretome. Future cardiac cell therapy approaches require a comprehensive understanding of myocardial senescence to improve therapeutic efficiency as well as efficacy.

Dementia with Lewy bodies (DLB) is the second most common form of dementia after Alzheimer disease (AD). DLB is characterized pathologically by Lewy body and Lewy neuritic pathology, often with variable levels of Alzheimer-type pathology. Core clinical features include fluctuating cognition, visual hallucinations, and parkinsonism resulting in greater impairments of quality of life, more caregiver burden, and higher health-related costs compared with AD. These issues, together with a high sensitivity to adverse events with treatment with antipsychotic agents, make the need for an early and accurate diagnosis of DLB essential. Unfortunately, current consensus criteria are highly specific but lack sufficient sensitivity. Use of composite risk scores may improve accuracy of clinical diagnosis. Imaging findings, particularly targeting dopaminergic systems have shown promise as potential markers to differentiate DLB from AD. A combination of non-pharmacologic treatments and pharmacotherapy interventions may maximize cognitive function and overall quality of life in DLB patients.

Gait and cognitive impairments in older adults mostly reflect the co-occurrence of two geriatric syndromes linked by common underlying brain substrates and pathologies. Gait control is predominately mediated by frontal subcortical circuits, which overlap with circuits controlling executive control and attention functions. These circuits are vulnerable to multiple age-related pathologies such as ischemia, inflammation, and neurodegeneration, which could ultimately cause cognitive, gait, or combined cognitive and gait impairments. The following review aims to describe various gait and cognitive classifications, gait based phenotypes, common underlying pathological processes, and provide a link between motor and cognitive impairments in an effort to predict the risk of dementia, as well as remediate impairments by applying appropriate interventions.

The purpose of this review is to highlight existing literature on the epidemiology, pathophysiology, and novel risk factors for vascular dementia. We further examine the evidence linking chronic brain hypoperfusion induced by a variety of cardiovascular diseases to the development of vascular dementia. In the elderly, in whom cerebral perfusion is diminished by the aging process, additional reduction in cerebral blood flow stemming from exposure to potentially modifiable vascular risk factors increases the probability of developing vascular dementia. Finally, we discuss the association between obstructive sleep apnea, an underrecognized risk factor for stroke, and vascular dementia. Obstructive sleep apnea is linked to cerebrovascular disease through many intermediary vascular risk factors and may directly cause cerebrovascular damage through microvacular disease. Insight into how cardiovascular risk factors induce vascular dementia offers an enhanced understanding of the multifactorial pathophysiology by this disorder and ways of preventing and managing the cerebrovascular precursors of vascular dementia. Many vital questions about the relation of obstructive sleep apnea with stroke and vascular dementia are still unanswered and await future well-designed studies.

Alzheimer's disease (AD) is a major cause of morbidity in the elderly. AD affects aver 5 million persons in the United States, but because it increases in incidence in the elderly, and the "graying" population, AD is projected to increase in prevalence by many-fold over the coming decades. AD causes progressive mental impairment, resulting in the inability of persons to care for themselves. As a consequence, AD results in enormous costs to society due to both lost productivity, and required care. Thus, improved management and treatment is essential. In this review we will briefly review current understanding of the disease, including roles of beta-amyloid and tau proteins. We will then discuss current therapies in use, including the evidence for treatments with supplements, established drugs, and investigational therapeutic strategies, recently completed and ongoing.