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

Novel wide array blood biomarkers of multisystem dysregulation, compared to conventional clinical and blood biomarkers, are potentially able to provide more accurate prognostic information of long-term mortality risks. We identified biomarker signatures of all-cause and disease-specific mortality from a comprehensive range of analytes related to six major physiological functions: cytokine, chemokine, and growth factors; glucose metabolism regulators and adipokines; adhesion molecules; acute phase response; pathogen-specific antibodies; and bone remodeling...

Background: Frailty is an important geriatric syndrome, but little is known about its development in the years preceding onset of the syndrome. The aim of this study was to examine the progression of frailty and compare the trajectories of each frailty component prior to frailty onset. Methods: Repeat data were from two cohort studies: the Longitudinal Aging Study Amsterdam (n = 1440) with a 15-year follow-up and the InCHIANTI Study (n = 998) with a 9-year follow-up...

Senescent cells are characterized by an increased secretion of inflammatory and growth factors, known as the "senescence-associated secretory phenotype" (SASP), producing a pro-tumoral and pro-angiogenic microenvironment. The present work proposes chronic resveratrol treatment (5 µM for 5 weeks, termed R5) of senescent MRC5 fibroblasts as a mean to mimic and target the angiogenic trait of stromal fibroblast SASP. Senescent fibroblast conditioned medium (CM sen) was effective in enhancing the angiogenic properties of endothelial colony forming cells (ECFC), i...

Depression is estimated to affect over 6.5 million Americans 65 years of age and older and compared to Non-Latino Whites older US Latinos have a greater incidence and severity of depression, warranting further investigation of novel risk factors for depression onset among this population. We used data on 771/1789 individuals ≥ 60 years of age from the Sacramento Area Latino Study on Aging (1998-2008) who were tested for cytomegalovirus (CMV), herpes simplex virus, varicella zoster, Helicobacter pylori, Toxoplasma gondii, and C-reactive protein (CRP) and interleukin-6 (IL-6) level...

Although the effects of physical exercise (PE) on cognitive function in dementia and mild cognitive impairment (MCI) have been largely studied, its biochemical effect is still poorly explored. The aim of this systematic review is to investigate the effects of PE on inflammatory, oxidative and neurotrophic biomarkers of subjects with MCI or dementia. Six electronic databases, (Pubmed, Cochrane Central, Embase, PEDro, PsycINFO and SportDiscus) were searched for randomized controlled trials assessing the effects of PE on serum/plasma biomarkers of elderly with MCI or dementia...

Background: The Drug Burden Index (DBI) calculates the total sedative and anticholinergic load of prescribed medications, and is associated with functional decline and hip fractures in older adults. However, it is unknown if confounding factors influence the relationship between the DBI and hip fractures. The objective of this study is to evaluate the association between the DBI and hip fractures, after correcting for mortality and multiple potential confounding factors. Methods: A competing risk regression analysis conducted on a prospectively recruited New Zealand community-dwelling older population who had a standardized (interRAI) assessment between 1 September 2012 and 31 October 2015, the study's end date...

We assembled a collection of 28,297 participants from 7 studies of longevity and healthy aging comprising New England Centenarian, Long Life Family, Longevity Gene Population, Southern Italian Centenarian, Japanese Centenarian, the Danish Longevity and the Health and Retirement Studies to investigate the association between the APOE alleles ɛ2, ɛ3 and ɛ4 and extreme human longevity and age at death. By using 3 different genetic models and two definitions of extreme longevity based on either a threshold model or age at death, we show that ɛ4 is associated with a substantially decreased odds for extreme longevity, and increased risk for death that persists even beyond ages reached by less than 1% of the population...

Background: Finding ways to quantify resilience as a predictor of a person's resistance to health challenges is important to improve healthy aging. This study investigated a unique sample of high-functioning older persons in whom traditional markers of frailty and functional decline are largely absent. Translating complex dynamical systems theory to humans, dynamical indicators of resilience (DIORs) in postural balance time series may sensitively discriminate levels of resilience. Methods: This study investigated 240 high-functioning older adults (mean age 83...

Background: Muscle weakness, as measured by handgrip strength, is associated with cardiovascular and all cause-mortality; however, there are wide inconsistences in the magnitude of these effects due to divergent definitions used to define muscle weakness across studies. Therefore, the objective of this study was to examine the relationship between previously defined sex- and race-specific cutpoints of clinical muscle weakness and early mortality. Methods: Data come from the 2006-2014 Health and Retirement Study...

Background: The beneficial effect of nut consumption preventing cardio-metabolic diseases and cancer suggests that nuts might also protect from physical function impairment in older people, since aging-related functional decline shares biological pathways with these chronic diseases. The objective was to examine the association between nut consumption and impairment of physical function in older adults. Methods: Prospective study with 3,289 individuals aged ≥60 years from the Seniors-ENRICA cohort...

We aimed to examine cellular and molecular changes in skeletal muscle of recreationally active older women in response to 24 weeks of combined resistance training and N-3 PUFA-rich healthy diet. Sixty-three women (65-70 years) were randomized into resistance training and healthy diet rich in N-3PUFAs (RT-HD), resistance training only (RT) and controls (CON). Fiber type-specific morphological characteristics and gene expression of inflammatory biomarkers and regulators of muscle mass were analyzed in m. vastus lateralis biopsies obtained before the intervention and 4 days after the last training session...

Human mesenchymal cells can become pluripotent by the addition of Yamanaka factors OCT3/4, SOX2, c-MYC, KLF4. We have recently reported that centenarians overexpress BCL-xL, which has been shown to improve pluripotency, thus we aimed to determine the expression of pluripotency-related genes in centenarians. We recruited 22 young, 32 octogenarian and 47 centenarian individuals and determined the mRNA expression of Yamanaka factors and other stemness-related cell surface marker genes (VIM, BMP4, NCAM, BMPR2) in peripheral blood mononuclear cells by reverse transcription polymerase chain reaction...

Polyphenols are promising nutritional bioactives exhibiting beneficial effect on age-related cognitive decline. The present study evaluated the effect of a polyphenol-rich extract from grape and blueberry (PEGB) on memory of healthy elderly subjects (60-70 years-old). A bicentric, randomized, double-blind, placebo-controlled trial was conducted with 215 volunteers receiving 600 mg/day of PEGB (containing 258 mg flavonoids) or a placebo for 6 months. The primary outcome was the CANTAB Paired Associate Learning (PAL), a visuospatial learning and episodic memory test...

Background: It is unclear whether older men with osteopenia/osteoporosis and sarcopenia (so called "osteosarcopenia") are at greater risk of falls and fractures than those with either condition alone. Methods: 1,575 community-dwelling men aged ≥70 years had appendicular lean mass, total hip and lumbar spine bone mineral density (BMD) determined by dual-energy X-ray absorptiometry, and completed hand grip strength and gait speed tests. Osteopenia/osteoporosis was defined as a T-score at any site ≤-1...

Background: We describe the recruitment of participants for Strategies to Reduce Injuries and Develop Confidence in Elders (STRIDE), a large pragmatic cluster randomized trial that is testing the effectiveness of a multifactorial intervention to prevent serious fall injuries. Eligible persons were 70 years or older, community-living, and at increased risk for serious fall injuries. The modified goal was to recruit 5,322 participants over 20 months from 86 primary care practices within 10 diverse health care systems across the United States...

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Peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) is a potent transcription factor for mitochondrial function, lipid metabolism, and detoxification in a variety of tissues. PGC1α also promotes brain cell proliferation and memory. However, how PGC1α is involved in aging is not well known. In brain endothelial cells, we found that PGC1α knockdown accelerated DNA damage-induced senescence, evidenced by an increase in senescence-associated γ-galactosidase-positive cells and a decrease in cell proliferation and ATP production...

Background: The Lifestyle Interventions and Independence for Elders (LIFE) clinical trial demonstrated that a structured program of physical activity (PA) reduced mobility-disability in older adults by up to 28%. It remains unknown whether the benefits of LIFE PA can be translated to older adults at risk for mobility-disability in real-world community-based settings. To address this knowledge gap, we conducted the ENGAGE pilot study and examined the safety, feasibility and preliminary effectiveness of translating LIFE PA to a community-based senior center...

Background: The relationship between levels of extracellular matrix (ECM) turnover and mortality is currently unknown. The study aimed to determine if levels of ECM turnover are predictors of all-cause mortality in a large cohort of post-menopausal women. Methods: 5,855 postmenopausal Danish women enrolled in the Prospective Epidemiologic Risk Factor (PERF) study. Baseline demographics and serum were collected at registration. Dates of death were obtained from the Danish Death Registry...

Background: Biologic age may better reflect an individual's rate of aging than chronologic age. Methods: We conducted a transcriptome-wide association study with biologic age estimated with clinical biomarkers, which included: systolic blood pressure, forced expiratory volume at one second (FEV1), total cholesterol, fasting glucose, C-reactive protein, and serum creatinine. We assessed the association between the difference between biologic age and chronologic age (∆age) and gene expression in whole blood measured using the Affymetrix Human Exon 1...