Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Aging of the organism is associated diminished response to external stimuli including weakened immune function, resulting in diseases that impair health and lifespan. Several dietary restriction modalities have been reported to improve health and lifespan in different animal models, but it is unknown whether any of the lifespan extending dietary treatment could be combined to achieve an additive effect. Here we investigated the effects of halving amino acids components in the HUNTaa diet, a synthetic medium known to extend lifespan in Drosophila...

Alzheimer's disease (AD) is a progressive, age-related neurodegenerative disorder that affects a large proportion of the elderly population. It currently lacks effective treatments, placing a heavy burden on patients, families, healthcare systems, and society. This is mainly due to our limited comprehension of the pathophysiology of AD progression, as well as the lack of effective drug targets and intervention timing to address the underlying pathology. AD is a multifactorial condition, and emerging evidence suggests that abnormalities in the gut microbiota play a significant role as environmental and multifaceted contributors to AD, although the exact mechanisms are yet to be fully explored...

Cellular senescence is a biological aging process that is exacerbated by obesity and leads to inflammation and age- and obesogenic-driven chronic diseases including type 2 diabetes. Caloric restriction (CR) may improve metabolic function in part by reducing cellular senescence and the pro-inflammatory senescence-associated phenotype (SASP). We conducted an ancillary investigation of an 18-week randomized controlled trial (RCT) of CR (n=31) or Control (n=27) in 58 middle-aged/older adults (57.6±5.8 years; 75% Women) with obesity and prediabetes...

BACKGROUND: Falls are a common cause of injury, hospitalisation, functional decline, and residential care admission among older adults. Cardiovascular disorders are recognised risk factors for falls. This systematic review assesses the association between cardiovascular disorders and falls in older adults. METHODS: Systematic searches were conducted on MEDLINE and EMBASE, encompassing all literature published prior to 31/12/2022. Included studies addressed persons aged 50 years and older, and assessed the association between cardiovascular disorders and falls or the efficacy of cardiovascular based interventions to reduce falls...

BACKGROUND: Consistent and reproducible estimates of the underlying true level of frailty are essential for risk stratification and monitoring of health changes. The purpose of this study is to examine the reliability of the frailty index (FI). METHODS: 426 community-dwelling older adults from the FRequent health Assessment In Later life (FRAIL70+) study in Austria were interviewed biweekly up to 7 times. Two versions of the FI, one with 49 deficits (baseline), another with 44 (follow-up) were created...

BACKGROUND: Age is the greatest risk factor for lower urinary tract symptoms attributed to benign prostatic hyperplasia (LUTS/BPH). While LUTS/BPH can be managed with pharmacotherapy, treatment failure has been putatively attributed to numerous pathological features of BPH (e.g., prostatic fibrosis, inflammation). Mitochondrial dysfunction is a hallmark of aging, however its impact on the pathological features of BPH remains unknown. METHODS: Publicly available gene array data was analyzed...

The appendicular extracellular-to-intracellular water ratio (A-E/I) is a potential marker of skeletal muscle quality, reflecting the balance of water distribution between the extracellular and intracellular compartments of the appendicular limb regions. A-E/I has been increasingly used in recent studies; however, its association with adverse outcomes remains unclear. This study investigated the potential association between A-E/I and all-cause mortality. A prospective cohort study of 8015 middle-aged and older adults (comprised of 4755 women, aged 45-74 years) residing in a Japanese community was conducted...

BACKGROUND: This study aims to examine temporal trends in frailty state transitions, and years spent frail, in older Swedish adults. METHODS: We followed Swedish National study on Aging and Care in Kungsholmen (SNAC-K) participants from baseline (2001-2004) for 15 (median: 9.6) years. A 40-deficit frailty index (FI) was constructed to identify three frailty states: robust (FI ≤ 0.125), mild frailty (0.125 < FI ≤ 0.25), and moderate and severe frailty (FI > 0...

BACKGROUND: We examined the relationship between Global Positioning System (GPS) indicators of community mobility and incident hospitalizations, emergency department (ED) visits, and falls over one year in community-dwelling older adults. METHODS: We performed a secondary analysis of a randomized trial investigating a physical therapy intervention to improve mobility in older adults. 148 participants (mean age: 76.9±6.2 years; 65% female) carried a GPS device following the post-intervention visit...

BACKGROUND: Antimicrobial peptides (AMPs) are key effectors of urinary tract innate immunity. Identifying differences in urinary AMP levels between younger and older adults is important in understanding older adults' susceptibility and response to urinary tract infections (UTI) and AMP use as diagnostic biomarkers. We hypothesized that uninfected older adults have higher urinary human neutrophil peptides 1-3 (HNP 1-3), human alpha-defensin-5 (HD-5), and human beta-defensin-2 (hBD-2), but lower urinary cathelicidin (LL-37) than younger adults...

While several antidepressants have been identified as potential geroprotectors, the effect and mechanism of fluoxetine, a representative selective serotonin reuptake inhibitor, on longevity have not been fully elucidated. Here, we found that fluoxetine promoted longevity in Caenorhabditis elegans (C. elegans) with a concomitant extension of a healthy lifespan as indicated by increasing mobility, reducing fertility and lipofuscin accumulation, and enhanced resistance to different abiotic stresses. Fluoxetine increased the level of reactive oxygen species (ROS), and antioxidant N-acetylcysteine abolished ROS elevation and the pro-longevity effect of fluoxetine...

Human society is aging, and the percentage of the population that is aged is increasing at an unprecedent rate. It is increasingly appreciated that social behaviors change with aging. One such example is the possible aging-related reduction in dominance status. This change has been thought to underlie aged adults' peculiar vulnerability to fraud, which has become a major challenge in the present aging society. However, whether this change is an inherent physiological process, and, if so, its underlying microscopic physiological mechanism, is not known...

BACKGROUND: Subjective cognitive decline (SCD) has gained recent interest as a potential harbinger of neurodegenerative diseases such as Alzheimer's disease (AD) and cerebrovascular disease (CVD). In addition, SCD can be related to depressive symptomatology. However, the association between AD and CVD biomarkers, depressive symptomatology, and SCD is still unclear. We investigated the association of AD and CVD biomarkers and depressive symptomatology with SCD in individuals with subjective memory complaints (SCD-memory group) and individuals with subjective concentration complaints (SCD-concentration group)...

Dynamic measures of resilience-the ability to resist and recover from a challenge-may be informative of the rate of aging before overt manifestations such as chronic disease, disability, and frailty. From this perspective mid-life resilience may predict longevity and late-life health. To test this hypothesis, we developed simple, reproducible, clinically relevant challenges and outcome measures of physical resilience that revealed differences between and within age groups of genetically heterogeneous mice, and then examined associations between mid-life resilience and both lifespan and late-life measures of physiological function...

This is the first known comparative assessment of the associations of epigenetic age estimates with the prevalence of rheumatoid arthritis. We used data available in Gene Expression Omnibus (GSE42861) from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study. Information regarding RA diagnosis and 450K DNA methylation (DNAm) of 18-to-70-year-old participants was available. Utilizing Horvath's online DNAm Age Calculator, we determined the DNAm estimate of Telomere length (DNAmTL), Hannum's epigenetic age, Horvath's 2013 and 2018 epigenetic ages, PhenoAge, GrimAge, and the respective age-acceleration measures...

BACKGROUND: Lower urinary tract symptoms (LUTS) and mobility limitations are bidirectionally associated among older adults, but the role of skeletal muscle remains unknown. We evaluated cross-sectional associations of muscle health and physical performance with LUTS. METHODS: We used data from 377 women and 264 men age>70 years in the Study of Muscle, Mobility and Aging (SOMMA). LUTS and urinary bother were assessed using the LURN Symptom Index-10 (SI-10;higher=worse symptoms)...

BACKGROUND: The relationship between amino acids (AA), B-vitamins, and their metabolites with D3-creatine dilution (D3Cr) muscle mass, a more direct measure of skeletal muscle mass, has not been investigated. We aimed to assess associations of plasma metabolites with D3Cr muscle mass, as well as muscle strength and physical performance in older men from the Osteoporotic Fractures in Men (MrOS) cohort study. METHODS: Out of 1,425 men (84.2±4.1yrs), men with the lowest D3Cr muscle mass (n=100), slowest walking speed (n=100), lowest grip strength (n=100), and a random sample (n=200) serving as a comparison group to the low groups were included...

Males and females rarely express the same length of life. Here we studied how socio-sexual exposure shapes male and female age-specific mortality rates in Drosophila melanogaster. We maintained focal females and males within large, replicated cohorts throughout life with individuals of the same or opposite sex. Consistent with previous works, we found that females kept throughout their lives with males had only half the lifespan of those maintained throughout life at the same density in same-sex cohorts. In contrast, only a small lifespan decrease was observed in the corresponding male treatments and the reduction in male lifespan following exposure throughout life to other males or to females was similar...

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BACKGROUND: Physical function and its decline in older age may be connected to treatable vascular risk factors in mid-life. This study aimed to evaluate whether these factors affect the underlying rate of decline. METHODS: This prospective cohort included 5,481 older adults aged 67 to 91 in the Atherosclerosis Risk in Communities (ARIC) Study (mean [SD] age=75.8 [5.0], 58% women, 21% Black race) without a history of stroke. The main outcome was rate of Short Physical Performance Battery (SPPB) decline over a median late-life follow-up of 4...