Palmer, Allyson K

Background/objectives: Falls are a leading cause of traumatic injury and hospitalization for adults over the age of 65. While common, bed-related falls are relatively understudied when compared to ambulatory falls. The aim of this study is to characterize the risk factors for the hospitalization of older adults presenting to U.S. emergency departments (EDs) after a fall from bed. Methods: This was a cross-sectional study using publicly available data from the U.S. Consumer Product Safety Commission’s National Electronic Injury Surveillance System (NEISS) from 2014 to 2023, including all adults over the age of 65 presenting to the NEISS’s participating EDs with bed-related fall injuries. We identified fall injuries using a keyword search of the NEISS narratives and determined how the fall occurred by manually reviewing a randomized 3% sample of the narratives. We summarized demographics and injury patterns with descriptive statistics. We constructed a multivariable logistic regression model to identify risk factors for hospitalization and used Poisson regression to assess temporal trends in fall incidence and hospital admissions. Results: An estimated average of 320,751 bed-related fall injuries presented to EDs annually from 2014 to 2023. ED visits increased by 2.85% per year, while hospital admissions rose by 5.67% per year (p < 0.001). The most common injury patterns were superficial injuries (contusions, abrasions, lacerations, avulsions, and punctures) (28.6%), fractures (21.7%), and internal injuries (including concussions) (21.6%). Most of the falls occurred while transitioning into or out of bed (34.4%) or falling out of bed (56.8%). Hospitalization was required in 34.1% of cases and was associated with male sex, medication use at time of injury, and fracture injuries. Conclusions: Bed-related falls and associated hospitalizations are increasing among older adults. ED providers should understand risk factors for hospitalization in these common injuries such as male sex, medication use at time of injury, and high-risk injury patterns. Additionally, prevention efforts should focus on helping older adults remain safely in bed and then assisting with transitions into or out of bed.

AbstractA robust and heterogenous secretory phenotype is a core feature of most senescent cells. In addition to mediators of age‐related pathology, components of the senescence associated secretory phenotype (SASP) have been studied as biomarkers of senescent cell burden and, in turn, biological age. Therefore, we hypothesized that circulating concentrations of candidate senescence biomarkers, including chemokines, cytokines, matrix remodeling proteins, and growth factors, could predict mortality in older adults. We assessed associations between plasma levels of 28 SASP proteins and risk of mortality over a median follow‐up of 6.3 years in 1923 patients 65 years of age or older with zero or one chronic condition at baseline. Overall, the five senescence biomarkers most strongly associated with an increased risk of death were GDF15, RAGE, VEGFA, PARC, and MMP2, after adjusting for age, sex, race, and the presence of one chronic condition. The combination of biomarkers and clinical and demographic covariates exhibited a significantly higher c‐statistic for risk of death (0.79, 95% confidence interval (CI): 0.76–0.82) than the covariates alone (0.70, CI: 0.67–0.74) (p < 0.001). Collectively, these findings lend further support to biomarkers of cellular senescence as informative predictors of clinically important health outcomes in older adults, including death.

Abstract The elderly population is increasing faster than other segments of the population throughout the world. Age is the leading predictor for most chronic diseases and disorders, multimorbidity, geriatric syndromes, and impaired ability to recover from accidents or illnesses. Enhancing the duration of health and independence, termed healthspan, would be more desirable than extending lifespan merely by prolonging the period of morbidity toward the end of life. The geroscience hypothesis posits that healthspan can be extended by targeting fundamental aging mechanisms, rather than attempting to address each age-related disease one at a time, only so the afflicted individual survives disabled and dies shortly afterward of another age-related disease. These fundamental aging mechanisms include, among others, chronic inflammation, fibrosis, stem cell/ progenitor dysfunction, DNA damage, epigenetic changes, metabolic shifts, destructive metabolite generation, mitochondrial dysfunction, misfolded or aggregated protein accumulation, and cellular senescence. These processes appear to be tightly interlinked, as targeting any one appears to affect many of the rest, underlying our Unitary Theory of Fundamental Aging Mechanisms. Interventions targeting many fundamental aging processes are being developed, including dietary manipulations, metformin, mTOR (mechanistic target of rapamycin) inhibitors, and senolytics, which are in early human trials. These interventions could lead to greater healthspan benefits than treating age-related diseases one at a time. To illustrate these points, we focus on cellular senescence and therapies in development to target senescent cells. Combining interventions targeting aging mechanisms with disease-specific drugs could result in more than additive benefits for currently difficult-to-treat or intractable diseases. More research attention needs to be devoted to targeting fundamental aging processes.

Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16INK4a promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span.

Senescent cells accumulate in fat with aging. We previously found genetic clearance of senescent cells from progeroid INK-ATTAC mice prevents lipodystrophy. Here we show that primary human senescent fat progenitors secrete activin A and directly inhibit adipogenesis in non-senescent progenitors. Blocking activin A partially restored lipid accumulation and expression of key adipogenic markers in differentiating progenitors exposed to senescent cells. Mouse fat tissue activin A increased with aging. Clearing senescent cells from 18-month-old naturally-aged INK-ATTAC mice reduced circulating activin A, blunted fat loss, and enhanced adipogenic transcription factor expression within 3 weeks. JAK inhibitor suppressed senescent cell activin A production and blunted senescent cell-mediated inhibition of adipogenesis. Eight weeks-treatment with ruxolitinib, an FDA-approved JAK1/2 inhibitor, reduced circulating activin A, preserved fat mass, reduced lipotoxicity, and increased insulin sensitivity in 22-month-old mice. Our study indicates targeting senescent cells or their products may alleviate age-related dysfunction of progenitors, adipose tissue, and metabolism.

Cellular senescence is a fundamental aging mechanism that has been implicated in many age-related diseases and is a significant cause of tissue dysfunction. Accumulation of senescent cells occurs during aging and is also seen in the context of obesity and diabetes. Senescent cells may play a role in type 2 diabetes pathogenesis through direct impact on pancreatic β-cell function, senescence-associated secretory phenotype (SASP)-mediated tissue damage, and involvement in adipose tissue dysfunction. In turn, metabolic and signaling changes seen in diabetes, such as high circulating glucose, altered lipid metabolism, and growth hormone axis perturbations, can promote senescent cell formation. Thus, senescent cells might be part of a pathogenic loop in diabetes, as both a cause and consequence of metabolic changes and tissue damage. Therapeutic targeting of a basic aging mechanism such as cellular senescence may have a large impact on disease pathogenesis and could be more effective in preventing the progression of diabetes complications than currently available therapies that have limited impact on already existing tissue damage. Therefore, senescent cells and the SASP represent significant opportunities for advancement in the prevention and treatment of type 2 diabetes and its complications.

AbstractEach year 610,000 cases of anogenital and oropharyngeal cancers caused by human papillomavirus (HPV) occur worldwide. HPV vaccination represents a promising opportunity to prevent cancer on a global scale. The vaccine's story dates back to discoveries in chickens at the beginning of the 20th century with evidence that a cell‐free filtrate could transmit the propensity to grow cancers. Later, studies with similarly derived filtrates from mammalian tumors showed that hosts could develop immunity to subsequent exposures. Epidemiologic studies linked cervical cancer to members of a family of viruses that cause papillomatosis and common warts. This led to work with DNA hybridization demonstrating a causal relationship. The formation of virus‐like particles from viral capsid proteins led to the development of models for safe and effective vaccines. While much work remains with the acceptance of universal vaccination, the HPV vaccines Gardasil and Cervarix thus represent a century of successful translational research.