Advances in geriatric medicine and research最新文献

The global population of 80 years and older is predicted to reach 437 million by 2050. As overall brain structure and function progressively degrades, older and younger adults show differences in sensorimotor performance and brain activity in the sensorimotor regions. Oral sensorimotor functions are an important area of focus in natural aging and Alzheimer's Disease (AD) because oral health issues are commonly found in both elderly and AD populations. While human behavioral studies on changes in oral sensorimotor functions abound, very little is known about their neuronal correlates in normal and pathological aging.

Cellular senescence has been found to have beneficial roles in development, tissue regeneration, and wound healing. However, in aging senescence increases, and the ability to properly repair and heal wounds significantly declines across multiple tissues. This age-related accumulation of senescent cells may cause loss of tissue homeostasis leading to dysregulation of normal and timely wound healing processes. The delays in wound healing of aging have widespread clinical and economic impacts, thus novel strategies to improve wound healing in aging are needed and targeting senescence may be a promising area.

The health of a cell requires proper functioning, regulation, and quality control of its organelles, the membrane-enclosed compartments inside the cell that carry out its essential biochemical tasks. Aging commonly perturbs organelle homeostasis, causing problems to cellular health that can spur the initiation and progression of degenerative diseases and related pathologies. Here, we discuss emerging evidence indicating that age-related defects in organelle homeostasis stem in part from dysfunction of the autophagy-lysosome system, a pivotal player in cellular quality control and damage clearance. We also highlight natural examples from biology where enhanced activity of the autophagy-lysosome system might be harnessed to erase age-related organelle damage, raising potential implications for cellular rejuvenation.

Similar to female reproductive health, male reproductive health declines with increasing age, albeit in a more gradual way. In the US, the average age of first-time fathers has been steadily increasing since 1980. This is concerning because increasing paternal age is positively correlated with reduced sperm chromatin quality and higher numbers of DNA strand breaks (DNA sb), which negatively affects pregnancy outcome and child development. While underlying reasons are not well understood, one of the well-known hallmarks of aging is a significant decline of body nicotinamide adenine dinucleotide (NAD) levels. We propose that low body-wide NAD levels provide a plausible explanation for metabolic alterations that are associated with declining hormonal production and testicular volume, as well as reduced sperm quality in aging men.

Frailty is a condition marked by greater susceptibility to adverse outcomes, including disability and mortality, which affects up to 50% of those 80 years of age and older. Concurrently, serum vitamin D insufficiency and deficiency, for which as many as 70% of older adults may be at risk, potentially play an important role in frailty onset and progression. Large population driven studies have uncovered associations between low serum vitamin D levels and higher incidence of frailty. However, attempts to apply vitamin D therapeutically to treat and/or prevent frailty have not yielded consistent support for benefits. Given the complexity and inconsistency arising from human studies involving vitamin D, our research group has recently published on animal models of vitamin D insufficiency. Combining our model with the emerging development of animal frailty assessment, we identified that higher than standard levels of vitamin D supplementation may delay frailty in mice. In this viewpoint article, we will discuss current knowledge regarding the importance of vitamin D in frailty progression, the emerging significance of animal models in addressing these relationships, and the future for pre-clinical and clinical research.

The eye and brain share common mechanisms of aging and disease, thus the retina is an essential source of accessible information about neurodegenerative processes occurring in the brain. Advances in retinal imaging have led to the discovery of many potential biomarkers of Alzheimer's disease, although further research is needed to validate these associations. Understanding the mechanisms of retinal disease in the context of aging will extend our knowledge of AD and may enable advancements in diagnosis, monitoring, and treatment.

Naïve T cells are critical for protection against emerging viral and bacterial infections. However, the ability of these cells to elicit effective long-term immune responses declines with age and contributes to increased disease susceptibility in older individuals. This decline has been linked with the breakdown of cellular quiescence that causes partial differentiation of naïve T cells with age, but the underlying mediators of this breakdown are unclear. Comparisons to stem cell quiescence in mice and man offer insight into naïve T cells and aging. However, the utilization of single cell technologies in combination with advances in the biology of human tissue aging is needed to provide further understanding of naïve T cell complexity and quiescence breakdown with age.

Women with chronic HIV infection (WWH) living in the United States, experience a disproportionately high rate of obesity compared to uninfected populations. Both overweight and obesity, particularly central obesity, are major contributors to insulin resistance, hypertension, and dyslipidemia-the major components of metabolic syndromes, including type 2 diabetes, and leading to increased cardiovascular risk, including coronary heart disease, and cerebrovascular diseases. Notably, declining physical performance and frailty co-occur with vascular morbidities as well as changes in bone. These factors tend to exacerbate each other and accelerate the aging trajectory, leading to poorer quality of life, cognitive impairments, dementia, and eventually, death. In WWH, persistent HIV infection, sustained treatment for HIV infection, and concomitant obesity, may accelerate aging-related morbidities and poorer aging outcomes. Furthermore, health disparities factors common among some WWH, are independently associated with obesity and higher vascular risk. The purpose of this review is to describe the constellation of obesity, cardio- and cerebrovascular diseases, bone health and frailty among aging WWH, a 21st century emergence.

Background: Options for Clostridioides difficile infection (CDI) refractory to conventional therapy are limited. Fecal microbiota transplant (FMT) is considered safe and effective treatment for recurrent CDI and could be a treatment option for refractory CDI. We investigated the efficacy and safety of FMT in hospitalized patients who were not responding to standard treatments for CDI.

Methods: Electronic medical records of patients who received FMT inpatient for refractory CDI were reviewed as part of quality improvement efforts to evaluate safety and efficacy of FMT in inpatient setting.

Results: Between July 2014 and December 2019, 9 patients (age 60-96) received FMT for CDI as inpatient for refractory or fulminant CDI. Most (7 of 9) of these patients had pseudomembranous colitis and underwent multiple FMTs (mean 2.15, range 1 to 3). Five patients had complete resolution and one patient had diarrhea that was C. difficile-negative. There was one recurrent CDI and two deaths, one of which may have been related to FMT or CDI. Compared to recurrent CDI at diagnosis, patients with refractory CDI had higher WBC and neutrophil counts, which decreased after FMT. The overall cure rate of FMT in refractory cases was 66.7%.

Conclusions: This study shows moderate efficacy of FMT for treatment of refractory CDI although multiple FMT treatment may need to be administered in the presence of pseudomembranous colitis. Inpatient FMT may be an alternative strategy for managing refractory CDI in this population of patients who may not have any effective medical treatment available.

As of December 2020, there were more than 900,000 COVID-19 hospitalizations in the US with about 414,000 among individuals aged 65 years and older. Recent evidence suggests a growing number of older patients continue to suffer serious neurological comorbidities including polyneuropathy, cerebrovascular disease, central nervous system infection, cognitive deficits, and fatigue following discharge. Studies suggest that complaints manifest late in disease and persist beyond resolution of acute COVID-19 symptoms. Recent research reports that neurocognitive symptoms are correlated with severe disease, older age, male gender, and comorbidities including hypertension, renal failure, and neoplastic disease. The underlying causes are unclear, but current hypotheses include hypoxic-ischemic brain injury, immunopathological mechanisms, and neurotropism of SARS-CoV-2 infection. There is a pressing need for more research into the underlying mechanisms of post-COVID-19 neurological sequela, particularly in the elderly, a population already burdened with neurocognitive disorders.