The journals of gerontology. Series A, Biological sciences and medical sciences最新文献

Background: Current multimorbidity measures often oversimplify complex disease interactions by assuming a merely additive impact of diseases on health outcomes. This oversimplification neglects clinical observations that certain disease combinations can exhibit synergistic effects. Thus, we aimed to incorporate simultaneous higher-order disease interactions into the validated ICD-coded multimorbidity-weighted index, to assess for model improvement.

Methods: Health and Retirement Study participants with linked Medicare data contributed ICD-9-CM claims, 1991-2012. Top 20 most prevalent and impactful conditions (based on associations with decline in physical functioning) were assessed through higher-order interactions (2-way, 3-way). We applied the least absolute shrinkage and selection operator and bootstrapping to identify and retain statistically significant disease interactions. We compared model fit in multimorbidity-weighted index with and without disease interactions in linear models.

Results: We analyzed 73 830 observations from 18 212 participants (training set N = 14 570, testing set N = 3 642). Multimorbidity-weighted index without interactions produced an overall R2 = 0.26. Introducing 2-way interactions for the top 10 most prevalent and impactful conditions resulted in a R2 = 0.27, while expanding to top 20 most prevalent and impactful conditions yielded a R2 = 0.26. When adding 3-way interactions, the same top 10 conditions produced a R2 = 0.26, while expanding to top 20 conditions resulted in a R2 = 0.24.

Conclusions: We present novel insights into simultaneous higher-order disease interactions for potential integration into multimorbidity measurement. Incorporating 2-way disease interactions for the top 10 most prevalent and impactful conditions showed a minimal improvement in model fit. A more precise multimorbidity index may incorporate both the main effects of diseases and their significant interactions.

Background: Denture use may contribute to maintaining cognitive function by addressing the masticatory difficulties caused by tooth loss. However, reports on the association between tooth loss and cognitive impairment have been inconsistent. The impact of changes in tooth number and denture use on the development of cognitive impairment in older adults remains unclear. This study aimed to evaluate these impacts among community-dwelling older adults.

Methods: This 7-year longitudinal prospective cohort study included 64 520 community-dwelling Taiwanese older adults aged ≥65 years without cognitive impairment at baseline. The primary outcome was cognitive impairment assessed using the Short Portable Mental Status Questionnaire.

Results: Older adults with 10-19, 1-9, and 0 teeth, including natural teeth and dentures, had higher risks of developing cognitive impairment than those with ≥20 teeth, with adjusted odds ratios (ORs) of 1.40 (95% confidence intervals [CIs], 1.14-1.71), 1.85 (95% CI, 1.40-2.43), and 2.56 (95% CI, 1.74-3.76), respectively. Furthermore, among those with 10-19 teeth (OR, 0.71; 95% CI, 0.52-0.98) or 1-9 teeth (OR, 0.43, 95% CI, 0.27-0.68) at baseline, an increase of more than 1 level in tooth number during follow-up (eg, from 10-19 to ≥ 20 teeth and dentures through the acquisition of dental prosthetics such as dentures, bridges, or implants) was associated with a lower risk of developing cognitive impairment compared with those with a stable tooth number.

Conclusions: Our findings suggest that prompt denture use and maintaining >20 teeth (including natural teeth and dentures) mitigate the risk of cognitive impairment associated with tooth loss among community-dwelling older adults.

Integrating antiretroviral therapy into HIV care dramatically extended the lifespan for people living with HIV. Improving the health span requires understanding aging, HIV, associated comorbid conditions, and concurrent treatments. The 14th annual International Workshop on HIV and Aging on October 26-27, 2023 included podium presentations on: Sarcopenia: Biology, Pathophysiology, Prevention and Treatment; Long-acting ART; Central Nervous System (CNS) complications; Asymptomatic Neurocognitive Impairment (ANI); Mental Health; Loneliness; and Resilience. Presentations highlighted persistent concerns for people living with HIV including sarcopenia and frailty, mental health, loneliness, and cognition. Presenters encouraged prioritizing mental health treatment, reducing social isolation, and research on resiliency.

Vascular aging, a common pathogenesis of senile chronic diseases, significantly increases morbidity and mortality in older adults; its intricate cellular and molecular mechanisms necessitate further investigation. Lumican (LUM) and integrin α2β1 are profibrotic extracellular matrix proteins and vital cell regulatory receptors, respectively. However, their roles in vascular aging remain unclear. This study sought to elucidate the connection between LUM and vascular aging as well as the biological mechanism of LUM/integrin α2β1 in this process. Using an enzyme-linked immunosorbent assay, we discovered that plasma LUM was elevated in vascular aging individuals and was positively correlated with brachial-ankle pulse wave velocity. Additionally, immunohistochemical and Western blot analyses confirmed LUM upregulation in arteries of older adults and aged mice, as well as in senescent vascular smooth cells (VSMCs). Wild-type and LUM semiknockout (Lum-/+) mice, along with primary VSMCs extracted from these mice, were exposed to angiotensin II to induce a stress-induced senescence model. LUM semiknockout mitigated angiotensin II-induced arteriosclerosis, hypertension, vascular aging, and remodeling in mice. Both in vitro and in vivo studies revealed that LUM deficiency suppressed p53, p21, collagen 1, and collagen 3 upregulation and synthetic phenotype formation in VSMCs stimulated by angiotensin II. Treating VSMCs with an integrin α2β1 antagonist reversed the aforementioned changes triggered by LUM proteins. Briefly, LUM functions as a potential marker and risk factor for vascular aging and promotes pathological changes by affecting integrin α2β1 in VSMCs. This study introduces a novel molecular target for the early diagnosis and treatment of vascular aging and age-related vascular diseases.

Background: Physiological networks are highly complex, integrating connections among multiple organ systems and their dynamic changes underlying human aging. It is unknown whether individual-level network could serve as robust biomarkers for health and aging.

Methods: We used personalized network analysis to construct a single-sample network and examine the associations between network properties and functional disability in the Rugao Longevity and Aging Study (RuLAS), the China Health and Retirement Longitudinal Study (CHARLS), the Chinese Longitudinal Healthy Longevity Survey (CLHLS), and the National Health and Nutrition Examination Survey (NHANES).

Results: We observed impairments in interconnected physiological systems among long-lived adults in RuLAS. Single-sample network analysis was applied to reflect the co-occurrence of these multisystem impairments at the individual level. The activities of daily living (ADL)-disabled individuals' networks exhibited notably increased connectivity among various biomarkers. Significant associations were found between network topology and functional disability across RuLAS, CHARLS, CLHLS, and NHANES. Additionally, network topology served as a novel biomarker to capture risks of incident ADL disability in CHARLS. Furthermore, these metrics of physiological network topology predicted mortality across 4 cohorts. Sensitivity analysis demonstrated that the prediction performance of network topology remained robust, regardless of the chosen biomarkers and parameters.

Conclusions: These findings showed that metrics of network topology were sensitive and robust biomarkers to capture risks of functional disability and mortality, highlighting the role of single-sample physiological networks as novel biomarkers for health and aging.

Background: Social risk factors are linked to adverse health outcomes, but their total impact on long-term quality of life is obscure. We hypothesized that a higher burden of social risk factors is associated with greater decline in quality of life over 10 years.

Methods: We examined associations between social risk factors count and decline >5 points in (i) physical component summary, and (ii) mental component summary scores from the Short Form-12 among Black and White participants in the Reasons for Geographic and Racial Differences in Stroke study (n = 14 401).

Results: For physical component summary, White participants with 1 social risk factor had relative risk (RR) for decline of 1.14 [95% confidence intervals (CI): 1.07-1.12]. Those with ≥2 social risk factors had RR of 1.26 [95% CI: 1.17-1.35], after adjusting for baseline demographics, health behaviors, medical conditions, medications, and physiological variables. Black participants with 1 social risk factor had RR of 1.03 [95% CI: 0.93-1.15]. Those with ≥2 social risk factors had RR of 1.24 [95% CI: 1.13-1.36]. For mental component summary, White participants with 1 social risk factor had RR for decline of 1.19 [95% CI: 1.04-1.37]. Those with ≥2 social risk factors had RR of 1.47 [95% CI: 1.28-1.68]. Black participants with 1 social risk factor had RR of 1.18 [95% CI: 0.96-1.45]. Those with ≥2 social risk factors had RR of 1.38 [95% CI: 1.14-1.66].

Conclusions: More social risk factors increased the risk of decline of quality of life for Black and White individuals, especially impacting mental health.

Normal aging is associated with significant deleterious cerebrovascular changes; these have been implicated in disease pathogenesis and increased susceptibility to ischemic injury. Although these changes are well documented in the brain, few studies have been conducted in the spinal cord. Here, we utilize specialized contrast-enhanced ultrasound (CEUS) imaging to investigate age-related changes in cervical spinal vascular anatomy and hemodynamics in male Fisher 344 rats, a common strain in aging research. Aged rats (24-26 months, N = 6) exhibited significant tortuosity in the anterior spinal artery and elevated vascular resistance compared to adults (4-6 months, N = 6; tortuosity index 2.20 ± 0.15 vs 4.74 ± 0.45, p < .05). Baseline blood volume was lower in both larger vessels and the microcirculation in the aged cohort, specifically in white matter (4.44e14 ± 1.37e13 vs 3.66e14 ± 2.64e13 CEUS bolus area under the curve, p < .05). To elucidate functional differences, animals were exposed to a hypoxia challenge, whereas adult rats exhibited significant functional hyperemia in both gray matter (GM) and white matter (WM) (GM: 1.13 ± 0.10-fold change from normoxia, p < .05; WM: 1.16 ± 0.13, p < .05), aged rats showed no response. Immunohistochemistry revealed reduced pericyte coverage and activated microglia behavior in aged rats, which may partially explain the lack of vascular response. This study provides the first in vivo description of age-related hemodynamic differences in the cervical spinal cord.

Background: Fall-related head impact is the leading cause of traumatic brain injury in older adults. There is limited understanding of factors related to fall-related head impact. This investigation examined characteristics of upper limb movements during standing-height falls and examined their association with fall-related head impact in older adults at risk for falls.

Methods: Older adults (n = 29) at risk for fall-related injuries underwent experimentally induced falls in multiple directions (backwards and sideways). To characterize the upper limb movements and their association with head impact, a standardized analysis tool was used to analyze a total of 164 video-recorded falls. The association between upper limb movements (and their characteristics) and head impact was analyzed through logistic regression.

Results: Nearly 80% of falls involved upper limb movements. Absence of upper limb movements significantly increased head impact odds by approximately 4-fold. The odds of head impact were reduced in falls with energy absorption at the forearm (0.013-fold) and upper arm (0.018-fold), compared to falls without upper limb energy absorption. Backwards falls showed significantly higher odds of head impact (more than 4-fold).

Conclusions: Upper limb movements are common during fall descent and are associated with lower odds of experiencing head impact. Energy absorption with the upper limb seems to be an important protective mechanism. Future work should explore if these movements can be augmented with targeted training.

Background: Biomarkers for sarcopenia are lacking. We examined the diagnostic power of serum creatinine to cystatin C ratio for identifying low magnetic resonance imaging-muscle volume and low grip strength in a large observational study of UK Biobank older adults.

Methods: Serum creatinine and cystatin C were measured via immunoassays (Beckman Coulter AU5800 and Siemens Advia 1800, respectively) and grip strength by hydraulic hand dynamometer at baseline visit (2008-2010). magnetic resonance imaging-thigh fat-free muscle volume and DXA-derived appendicular lean mass were measured at imaging visit (2014-2018). Extreme outliers were removed, and covariates (demographic, lifestyle, and clinical factors, as well as time elapsed between baseline-imaging visit) were adjusted for in statistical models.

Results: 12 873 older adults (mean age: 63.5 ± 2.7 years, 44.2% women) were included for fat-free muscle volume and appendicular lean mass/body mass index; 149 707 older adults (mean age: 64.0 ± 2.9 years, 50.5% women) for grip strength. Despite significant associations (p < .05), in fully adjusted models, creatinine to cystatin C showed poor to acceptable diagnostic power for identifying low fat-free muscle volume when using cutpoints of 20th percentile (area under the curve: 0.577 men; 0.622 women) and T scores of -2 (area under the curve: 0.596 men; 0.659 women) and -2.5 (area under the curve: 0.609 men; 0.722 women). In fully adjusted model, creatinine to cystatin C showed poor diagnostic power (area under the curves: <0.70) for identifying low appendicular lean mass/body mass index or low grip strength, irrespective of the cutpoint used.

Conclusions: Creatinine to cystatin C may not be a suitable biomarker for identifying low muscle volume or low strength in older adults. This finding, drawn from a large sample size and the use of advanced medical imaging, marks an important contribution to the sarcopenia field.