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

Background: Multidimensional prognostic index (MPI) is useful as prognostic tool in hospitalized older patients, but our knowledge derived from retrospective studies. We therefore aimed to evaluate in a multi-center, longitudinal, cohort study whether the MPI at hospital admission is useful to identify groups with different mortality risk and whether MPI at discharge may predict institutionalization, re-hospitalization and use of homecare services during 12 months. Methods: This longitudinal study, carried-out between February 2015 and August 2017, included nine public hospitals in Europe and Australia...

The key objective of this work was to investigate the impact of young and old human lymphocyte secretomes on C2C12 myoblasts regeneration. Conditioned media (CMs) were harvested from isolated young and older lymphocytes treated with (activated AC), or without (non-activated NA), anti-CD3/CD28 activators for 4 days. AC conditioned media from older lymphocytes had decreased levels of amphiregulin (367±208pg/ml vs. 904±323pg/ml; p=0.018) and IGF-I (845±88ng/ml vs. 1100±48ng/ml; p=0.032) compared with younger AC...

We evaluated whether the marmoset, a nonhuman primate, can serve as a good model to study aging related changes in the kidney by employing healthy young and aged marmosets of both sexes. Aging was associated with glomerulosclerosis, interstitial fibrosis and arteriolosclerosis in both sexes; correspondingly, the content of matrix proteins was increased. Functionally, aging resulted in an increase in urinary albumin and protein excretion. There was a robust correlation between markers of fibrosis and functional changes...

Candidate gene studies and genome-wide association studies found that genetic variation in APOE is robustly associated with multiple age-related diseases and longevity. Apolipoprotein E (ApoE) is an apolipoprotein that plays an important role in triglyceride and cholesterol metabolism. In literature, especially the ApoE ɛ4 isoform has been associated with an increased risk of mortality and age-related diseases such as Alzheimer's disease (AD), cardiovascular diseases (CVD), as compared to the "neutral" ApoE ɛ3 isoform...

Background: Incidence rates of dementia appear to be declining in high-income countries according to several large epidemiological studies. We aimed to describe declining incident dementia rates across successive birth cohorts in a U.S. population-based sample and to explore the influences of sex and education on these trends. Methods: We pooled data from two community-sampled prospective cohort studies with similar study aims and contiguous sampling regions: the Monongahela Valley Independent Elders Survey (1987-2001) and the Monongahela-Youghiogheny Healthy Aging Team (2006-Ongoing)...

Background: The accumulation of advanced glycation end product (AGE) might exert deleterious effects on musculoskeletal properties. Our study aims to clarify this possible association in a large general population. Methods: This study investigated a general population of 9,203 patients (mean age, 57.8 years). Skeletal muscle mass was measured by bioelectrical impedance analysis, whereas accumulation of AGEs was assessed by skin autofluorescence (SAF-AGE). The muscle strength of upper and lower limbs and usual gait speed were measured in a portion of older (≥60 years of age) participants (n = 1,934)...

Background: Evidence pertaining to whether more recent born generations of adults reaching old age have better physical capability than previous generations is scarce and inconclusive. We aimed to investigate birth cohort differences in grip strength. Methods: The study comprised 5,595 individuals from the Tromsø study waves in 1994/1995, 2007/2008, and 2015/2016. Grip strength (bar) was measured using a Martin vigorimeter, and compared across three birth cohorts of 66- to 84-year-olds (born in: 1910-1929, 1923-1942, 1931-1949), as well as within narrower age bands to ensure nonoverlapping cohorts...

Background: Frailty is a key determinant of clinical outcomes. We sought to describe frailty among U.S. Veterans and its association with mortality. Methods: Nationwide retrospective cohort study of regular Veterans Affairs (VA) users, aged at least 65 years in 2002-2012, followed through 2014, using national VA administrative and Medicare/Medicaid data. A frailty index (FI) for VA (VA-FI) was calculated using the cumulative deficit method. Thirty-one age-related deficits in health from diagnostic and procedure codes were included and were updated biennially...

Mesenchymal stem cell (MSC) grafting is a highly promising alternative strategy for periodontal regeneration in periodontitis, which is one of the primary causes of tooth loss in the elderly. However, aging progressively decreases the proliferative and differentiation potential of MSCs and diminishes their regenerative capacity, which represents a limiting factor for their endogenous use in elderly patients. Therefore, tissue regeneration therapy with MSCs in this age group may require a cellular source without the physiological limitations that MSCs exhibit in aging...

The purpose of this study is to compare the effect of unpredictable (U) or predictable (P) food delivery on health and longevity in mice. From 2 months of age until end of life, singly-housed male C57BL/6 mice were fed a semisynthetic diet either ad libitum (AL), or as imposed meals delivered as small pellets at either P or U times, frequencies, or amounts. The total daily food consumed by all groups was the same. The AL group gained body weight faster than either P or U groups, and had ~12% shorter median life span compared with either P or U groups...

Background: The Short Physical Performance Battery (SPPB) is advocated as a screening tool in geriatric care for predicting future disability. We aimed to identify the leg neuromuscular attributes to be targeted in rehabilitative care among older adults with poor SPPB scores. Methods: Boston Rehabilitative Impairment Study of the Elderly (Boston RISE) participants (n = 430) underwent assessment of neuromuscular attributes (leg strength, leg velocity, trunk extensor endurance, knee flexion range of motion [ROM], ankle ROM, and foot sensation)...

The ribosome has a lateral stalk which consists of rpLP0, rpLP1, and rpLP2. One of these proteins, rpLP2, is decreased in translating ribosome when cellular senescence is induced. Y-box binding protein-1 (YB-1) is also reduced in polysomal fraction of senescent cells. We discovered that rpLP2 depletion in the ribosome can cause the detachment of YB-1 in polysomes and that it is linked to cellular senescence. Our results also revealed that a decrement of CK2α or GRK2 in senescent cells induced an increment of unphosphorylated rpLP2, resulting in release of YB-1 from polysomes...

Ageing is characterized by a progressive decline in immune function known as immunosenescence (IS). While the causes of IS are likely to be multi-factorial, an age-associated accumulation of senescent T-cells and decreased naïve T-cell repertoire are key contributors to the phenomenon. On the other hand, there is a growing consensus that physical exercise may improve immune response in ageing. However, the optimum training modality required to obtain beneficial adaptations in older subjects is lacking. Therefore, we aimed to investigate the effects of exercise modality on T-cell phenotypes in older women...

Background: The Late-Life Function and Disability Instrument (LLFDI) is a well-validated and frequently used patient-reported outcome for older adults. The aim of this study was to estimate the minimal clinically important difference of the LLFDI-Function Component (LLFDI-FC) and its subscales among community-dwelling older adults with mobility limitations. Methods: We performed a secondary analysis of the Boston Rehabilitative Impairment Study of the Elderly, a longitudinal cohort study of older adults with mobility limitations residing in the community...

Physical activity has positive effects on brain health and cognitive function throughout the life span. Thus far, few studies have examined the effects of physical activity on white matter microstructure and psychomotor speed within the same, population-based sample (critical if conclusions are to extend to the wider population). Here, using diffusion tensor imaging and a simple reaction time task within a relatively large population-derived sample (N = 399; 18-87 years) from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN), we demonstrate that physical activity mediates the effect of age on white matter integrity, measured with fractional anisotropy...

We evaluated effects of calorie restriction (CR: consuming 60-65% of ad libitum [AL] intake) initiated late-in-life with or without acute exercise on insulin-stimulated glucose uptake (ISGU) of skeletal muscle by studying 4 groups of 26-month-old rats: sedentary-AL, sedentary-CR (8-week duration), 3-hours post-exercise (3hPEX)-AL and 3hPEX-CR. ISGU was determined in isolated epitrochlearis muscles incubated ±insulin. Muscles were assessed for signaling proteins (immunoblotting) and lipids (mass spectrometry)...

Alzheimer's disease (AD) is the most widespread late-life dementia and involves the prefrontal cortex, a vulnerable brain region implicated in memory, emotion, cognition, and decision-making behavior. To understand the molecular differences between the effects of aging and AD on the prefrontal cortex, this study characterized the age-dependent changes in gene expression in Wistar rats (control) and OXYS rats (rodents that simulate key characteristics of sporadic AD) using RNA sequencing. We found that major altered biological processes during aging in Wistar rats were associated with immune processes...

Background: It is unknown whether observational studies evaluating the association between antidiabetic medications and mortality adequately account for frailty. Our objectives were to evaluate if frailty was a potential confounder in the relationship between antidiabetic medication regimen and mortality and how well administrative and clinical electronic health record (EHR) data account for frailty. Methods: We conducted a retrospective cohort study in a single Veterans Health Administration (VHA) healthcare system of 500 hospitalizations - the majority due to heart failure - of Veterans who received regular VHA care and initiated type 2 diabetes treatment from 2001-2008...

Background: We have previously shown that vitamin D supplementation increases telomerase activity, suggesting an anti-aging effect. In this study, we aim to test the hypothesis that vitamin D supplementation would slow down epigenetic aging, a new marker of biological aging. Methods: A randomized clinical trial was previously conducted among 70 overweight/obese African-Americans with serum 25-hydroxyvitamin D [25(OH)D]<50 nmol/L, who were randomly assigned into four groups of 600 IU/day, 2000 IU/day, 4000 IU/day of vitamin D3 supplements or placebo followed by 16-weeks interventions...

rTMS and MSCs transplantation both showed therapeutic effects on cognition impairment in vascular dementia model rats. However, whether these two therapies have synergistic effects and the molecular mechanisms remain unclear. In our present study, rats were randomly divided into six groups: control group, sham operation group, VD group, MSC group, rTMS group and MSC+rTMS group. The VD model rats were prepared using a modified 2VO method. rTMS treatment was implemented at a frequency of 5 Hz, the stimulation intensity for 0...