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Cellular senescence is a plausible mediator of age-associated declines in physical performance. To test this premise, we examined cross-sectional associations between circulating components of the senescence-associated secretory phenotype (SASP) and measures of physical function and muscle strength in 1377 older adults. We showed significant associations between multiple SASP proteins and the short physical performance battery (SPPB), its subcomponents (gait speed, balance, chair rise time), and 400-m walk time. Activin A, ICAM1, MMP7, VEGFA, and eotaxin showed strong associations based on gradient boost machine learning (GBM), and, when combined with other proteins, effectively identified participants at the greatest risk for mobility disability (SPPB score ≤7). Senescence biomarkers were also associated with lower grip strength, and GBM identified PARC, ADAMTS13, and RANTES as top candidates in females, and MMP2, SOST, and MCP1 in males. These findings highlight an association between senescence biomarkers and physical performance in older adults. ClinicalTrials.gov Identifier: NCT01072500.

Objective: The objective of the study was to investigate functional performance and pain intensity outcomes for associations with negative cognitive orientations, avoidance behaviors, and fear of pain in older Black men with low back pain (LBP). Methods: Sixty Black men aged 60 and older (70 years$\pm 6$\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\pm 6$$\end{document}) with LBP completed the Short Physical Performance Battery (SPPB), the 400-m walk test, and subjective measures of avoidance behaviors, back performance, pain intensity, and pain catastrophizing (i.e., rumination, magnification, and helplessness). Multiple regression models were used to examine associations. Results: Higher helplessness scores were associated with worse back performance (ß= 0.55, p= 0.02), slower walking speed (ß= 0.30, p= 0.02), and higher average pain intensity (ß= 0.22, \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$\mathrm{API},$$\end{document}p= 0.03). Higher rumination scores were associated with better back performance (ß=  − 0.36, p= 0.04). Avoidance behaviors, fear of pain, and magnification were not significantly associated with any of the variables included in the tested models. Conclusion: Negative cognitive internalization is associated with limitations in functional performance in older Black men with LBP. Additional research is needed to further examine the cognitive orientations for understanding experienced pain and function in this population. Such research may inform the development of interventions for improving functional performance outcomes of older Black men with LBP.

Prostate-specific antigen (PSA) changes during testosterone treatment of older hypogonadal men have not been rigorously evaluated.

Declines in walking speed are associated with a variety of poor health outcomes including disability, comorbidity, and mortality. While genetic factors are putative contributors to variability in walking, few genetic loci have been identified for this trait. We examined the role of mitochondrial genomic variation on walking speed by sequencing the entire mitochondrial DNA (mtDNA). Data were meta-analyzed from 1758 Lifestyle Interventions and Independence for Elders (LIFE) Study and replication data from 730 Health, Aging, and Body Composition (HABC) Study participants with baseline walking speed information. Participants were 69+ years old of diverse racial backgrounds (African, European, and other race/ethnic groups) and had a wide range of mean walking speeds [4–6 m (0.78–1.09 m/s) and 400 m (0.83–1.24 m/s)]. Meta-analysis across studies and racial groups showed that m.12705C>T, ND5variant was significantly associated (p< 0.0001) with walking speed at both short and long distances. Replication and meta-analysis also identified statistically significant walking speed associations (p< 0.0001) between the m.5460.G>A, ND2and m.309C>CT, HV2 variants at short and long distances, respectively. All results remained statistically significant after multiple comparisons adjustment for 499 mtDNA variants. The m.12705C>T variant can be traced to the beginnings of human global migration and that cells carrying this variant display altered tRNA expression. Significant pooled effects related to stopping during the long-distance walk test were observed across OXPHOS complexes I (p= 0.0017) and III (p= 0.0048). These results suggest that mtDNA-encoded variants are associated with differences in walking speed among older adults, potentially identifying those at risk of developing mobility impairments.

The Physical Function Trial (PFT) was one of seven Testosterone Trials (TTrials), the aim of which was to assess the effect of testosterone on mobility, self-reported physical function, falls, and patient global impression-of-change (PGIC) in older men with low testosterone concentrations, self-reported mobility limitation, and walking speed of less than 1·2 m/s. Using data from the PFT and the overall TTrials study population, we also aimed to identify whether the effect of testosterone on mobility differed according to baseline walking speed, mobility limitation, or other participant-level factors.

Sarcopenia, the degenerative loss of skeletal muscle mass, quality and strength, lacks early diagnostic tools and new therapeutic strategies to prevent the frailty-to-disability transition often responsible for the medical institutionalization of elderly individuals. Herein we report that production of the endogenous peptide apelin, induced by muscle contraction, is reduced in an age-dependent manner in humans and rodents and is positively associated with the beneficial effects of exercise in older persons. Mice deficient in either apelin or its receptor (APLNR) presented dramatic alterations in muscle function with increasing age. Various strategies that restored apelin signaling during aging further demonstrated that this peptide considerably enhanced muscle function by triggering mitochondriogenesis, autophagy and anti-inflammatory pathways in myofibers as well as enhancing the regenerative capacity by targeting muscle stem cells. Taken together, these findings revealed positive regulatory feedback between physical activity, apelin and muscle function and identified apelin both as a tool for diagnosis of early sarcopenia and as the target of an innovative pharmacological strategy to prevent age-associated muscle weakness and restore physical autonomy.

The Testosterone Trials (TTrials) were a coordinated set of seven placebo-controlled, double-blind trials in 788 men with a mean age of 72 years to determine the efficacy of increasing the testosterone levels of older men with low testosterone. Testosterone treatment increased the median testosterone level from unequivocally low at baseline to midnormal for young men after 3 months and maintained that level until month 12. In the Sexual Function Trial, testosterone increased sexual activity, sexual desire, and erectile function. In the Physical Function Trial, testosterone did not increase the distance walked in 6 minutes in men whose walk speed was slow; however, in all TTrial participants, testosterone did increase the distance walked. In the Vitality Trial, testosterone did not increase energy but slightly improved mood and depressive symptoms. In the Cognitive Function Trial, testosterone did not improve cognitive function. In the Anemia Trial, testosterone increased hemoglobin in both men who had anemia of a known cause and in men with unexplained anemia. In the Bone Trial, testosterone increased volumetric bone mineral density and the estimated strength of the spine and hip. In the Cardiovascular Trial, testosterone increased the coronary artery noncalcified plaque volume as assessed using computed tomographic angiography. Although testosterone was not associated with more cardiovascular or prostate adverse events than placebo, a trial of a much larger number of men for a much longer period would be necessary to determine whether testosterone increases cardiovascular or prostate risk.The Testosterone Trials were conducted to determine if testosterone treatment would benefit older men with low testosterone. This report describes the Trials’ development and results and the lessons learned.

Clinical trials of older adults are increasingly common, but risks of serious adverse events (SAE) may vary. We describe the incidence of SAE in two randomized trials, one community-based and one nursing home-based.

Studies of the possible cardiovascular risk of testosterone treatment are inconclusive.

Skeletal muscle mitochondrial function declines with age and is a key factor in the maintenance of physical function among older adults. Research studies from animals and humans have consistently demonstrated that exercise improves skeletal muscle mitochondrial function in early and middle adulthood. However, mitochondrial adaptations to both acute and chronic exercise are attenuated in late life. Thus, there is an important need to identify adjuvant therapies capable of augmenting mitochondrial adaptations to exercise (e.g. improved mitochondrial respiration, muscle mitochondria biogenesis) among older adults. This study is investigating the potential of resveratrol supplementation for this purpose. The objective of this randomized, double-masked pilot trial is to evaluate the efficacy of resveratrol supplementation combined with a comprehensive supervised exercise program exercise for improving physical function among older adults. Moderately functioning, sedentary participants aged ≥60 years will perform 24 sessions (2 day/wk for 12 weeks) of center-based walking and resistance training and are randomly assigned to receive either (1) 500 mg/day resveratrol (2) 1000 mg/day resveratrol or (3) placebo. Study dependent outcomes include changes in 1) knee extensor strength, 2) objective measures of physical function (e.g. 4 m walk test, Short Physical Performance Battery), 3) subjective measures of physical function assessed by Late Life Function and Disability Instrument, and 4) skeletal muscle mitochondrial function. This study will provide novel information regarding the therapeutic potential of resveratrol supplementation combined with exercise while also informing about the long-term clinical viability of the intervention by evaluating participant safety and willingness to engage in the intervention.

IMPORTANCE: In one-third of older men with anemia, no recognized cause can be found. OBJECTIVE: To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone levels and unexplained anemia would increase their hemoglobin concentration. DESIGN, SETTING, AND PARTICIPANTS: A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≤12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. INTERVENTIONS: Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES: The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. RESULTS: The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. CONCLUSIONS AND RELEVANCE: Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617

Greater hippocampal volume is observed in healthy older adults after short-term structured exercise. Whether long-term exposure to real-world physical activity (PA) programs has similar effects for sedentary older adults with impaired mobility and comorbid conditions is not known.

Sarcopenia, the age-dependent loss of muscle mass and function, is a common condition among older adults, and is associated with several adverse health outcomes. Owing to the impact of sarcopenia on quality of life, disability and mortality, a greater awareness is necessary in order to correctly identify the condition both in community and geriatric settings. Research on sarcopenia prevention and treatment is developing quickly, but many questions are still unanswered. The core of the sarcopenia condition involves quantitative and qualitative losses of skeletal muscle. These two dimensions should therefore be considered when designing and testing preventive and therapeutic interventions. The recently released operationalization of sarcopenia by the Foundation for the National Institutes of Health (FNIH) Sarcopenia Project allows for the framing of an objective, standardized, and clinically relevant condition, which should facilitate its translation into the clinical arena as well as its adoption by public health and regulatory agencies. Such a conceptualization might eventually encourage key stakeholders to combine their efforts in approaching the sarcopenia condition. Bearing these considerations in mind, the “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies” project has operationalized a specific condition, named physical frailty and sarcopenia (PF&S), characterized by the combination of low physical performance (based on the Short Physical Performance Battery) and low muscle mass (according to the FNIH cut-points). A randomized controlled trial will be conducted to evaluate the efficacy of a multi-component intervention for preventing mobility disability and other adverse health outcomes in older adults with PF&S.

In the present article, the rationale that guided the operationalization of the theoretical concept of physical frailty and sarcopenia (PF&S), the condition of interest for the “Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies” (SPRINTT) trial, is presented. In particular, the decisions lead to the choice of the adopted instruments, and the reasons for setting the relevant thresholds are explained. In SPRINTT, the concept of physical frailty is translated with a Short Physical Performance Battery score of ≥3 and ≤9. Concurrently, sarcopenia is defined according to the recent definitions of low muscle mass proposed by the Foundation for the National Institutes of Health—Sarcopenia Project. Given the preventive purpose of SPRINTT, older persons with mobility disability (operationalized as incapacity to complete a 400-m walk test within 15 min; primary outcome of the trial) at the baseline are not included within the diagnostic spectrum of PF&S.

The sustainability of health and social care systems is threatened by a growing population of older persons with heterogeneous needs related to multimorbidity, frailty, and increased risk of functional impairment. Since disability is difficult to reverse in old age and is extremely burdensome for individuals and society, novel strategies should be devised to preserve adequate levels of function and independence in late life. The development of mobility disability, an early event in the disablement process, precedes and predicts more severe forms of inability. Its prevention is, therefore, critical to impede the transition to overt disability. For this reason, the Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment strategies (SPRINTT) project is conducting a randomized controlled trial (RCT) to test a multicomponent intervention (MCI) specifically designed to prevent mobility disability in high-risk older persons. SPRINTT is a phase III, multicenter RCT aimed at comparing the efficacy of a MCI, based on long-term structured physical activity, nutritional counseling/dietary intervention, and an information and communication technology intervention, versus a healthy aging lifestyle education program designed to prevent mobility disability in 1500 older persons with physical frailty and sarcopenia who will be followed for up to 36 months. The primary outcome of the SPRINTT trial is mobility disability, operationalized as the inability to walk for 400 m within 15 min, without sitting, help of another person, or the use of a walker. Secondary outcomes include changes in muscle mass and strength, persistent mobility disability, falls and injurious falls, disability in activities of daily living, nutritional status, cognition, mood, the use of healthcare resources, cost-effectiveness analysis, quality of life, and mortality rate. SPRINTT results are expected to promote significant advancements in the management of frail older persons at high risk of disability from both clinical and regulatory perspectives. The findings are also projected to pave the way for major investments in the field of disability prevention in old age.

The identification of cost-effective interventions that improve the health status and prevent disability in old age is one of the most important public health challenges. Regular physical activity is the only intervention that has consistently been shown to improve functional health and energy balance and to reduce the risk of cardiovascular disease, stroke, diabetes, several cancers, depression and falls. In advanced age, physical activity is also effective at mitigating sarcopenia, restoring robustness, and preventing/delaying the development of disability. On the other hand, physical inactivity is recognized as one of the leading causes of several chronic degenerative diseases and is also a major contributing factor to sarcopenia and functional disability. This compelling evidence has prompted the World Health Organization to recommend engaging in regular physical activity throughout one’s life course. The present review summarizes the available evidence in support of physical activity as a remedy against physical frailty and sarcopenia. The relevant pathways through which the benefits of physical activity are conveyed are also discussed.

IMPORTANCE: Whether sustained physical activity prevents cardiovascular disease (CVD) events in older adults is uncertain. OBJECTIVE: To test the hypothesis that cardiovascular morbidity and mortality would be reduced in participants in a long-term physical activity program. DESIGN, SETTING, AND PARTICIPANTS: The Lifestyle Interventions and Independence for Elders (LIFE) study was a multicenter, randomized trial. Participants were recruited at 8 centers in the United States. We randomized 1635 sedentary men and women aged 70 to 89 years with a Short Physical Performance Battery (SPPB) score of 9 or less but able to walk 400 m. INTERVENTIONS: The physcial activity (PA) intervention was a structured moderate-intensity program, predominantly walking 2 times per week on site for 2.6 years on average. The successful aging intervention consisted of weekly health education sessions for 6 months, then monthly. MAIN OUTCOMES AND MEASURES: Total CVD events, including fatal and nonfatal myocardial infarction, angina, stroke, transient ischemic attack, and peripheral artery disease, were adjudicated by committee, and silent myocardial infarction was assessed by serial electrocardiograms. A limited outcome of myocardial infarction, stroke, and CVD death was also studied. Outcome assessors and adjudicators were blinded to intervention assignment. RESULTS: The 1635 LIFE study participants were predominantly women (67%), with a mean (SD) age of 78.7 (5.2) years; 20% were African-American, 6% were Hispanic or other race or ethnic group, and 74% were non-Latino white. New CVD events occurred in 121 of 818 PA participants (14.8%) and 113 of 817 successful aging participants (13.8%) (HR, 1.10; 95% CI, 0.85-1.42). For the more focused combined outcome of myocardial infarction, stroke, or cardiovascular death, rates were 4.6% in PA and 4.5% in the successful aging group (HR, 1.05; 95% CI, 0.67-1.66). Among frailer participants with an SPPB score less than 8, total CVD rates were 14.2% in PA vs 17.7% in successful aging (HR, 0.76; 95% CI, 0.52-1.10), compared with 15.3% vs 10.5% among those with an SPPB score of 8 or 9 (HR, 1.59; 95% CI, 1.09-2.30) (P for interaction = .006). With the limited end point, the interaction was not significant (P = .59), with an HR of 0.94 (95% CI, 0.50-1.75) for an SPPB score less than 8 and an HR of 1.20 (95% CI, 0.62-2.34) for an SBBP score of 8 or 9. CONCLUSIONS AND RELEVANCE: Among participants in the LIFE Study, an aerobically based, moderately intensive PA program was not associated with reduced cardiovascular events in spite of the intervention’s previously documented ability to prevent mobility disability. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00116194.

Context:The Testosterone Trials are a coordinated set of seven trials to determine the efficacy of T in symptomatic men ≥65 years old with unequivocally low T levels. Initial results of the Sexual Function Trial showed that T improved sexual activity, sexual desire, and erectile function.Objective:To assess the responsiveness of specific sexual activities to T treatment; to relate hormone changes to changes in sexual function; and to determine predictive baseline characteristics and T threshold for sexual outcomes.Design:A placebo-controlled trial.Setting:Twelve academic medical centers in the United States.Participants:A total of 470 men ≥65 years of age with low libido, average T <275 ng/dL, and a partner willing to have sexual intercourse at least twice a month.Methods:Men were assigned to take T gel or placebo for 1 year. Sexual function was assessed by three questionnaires every 3 months: the Psychosexual Daily Questionnaire, the Derogatis Interview for Sexual Function, and the International Index of Erectile Function.Results:Compared with placebo, T administration significantly improved 10 of 12 measures of sexual activity. Incremental increases in total and free T and estradiol levels were associated with improvements in sexual activity and desire, but not erectile function. No threshold T level was observed for any outcome, and none of the 27 baseline characteristics predicted responsiveness to T.Conclusions:In older men with low libido and low T levels, improvements in sexual desire and activity in response to T treatment were related to the magnitude of increases in T and estradiol levels, but there was no clear evidence of a threshold effect.

Context:The optimal frequency for on-treatment serum T measurement used for dose adjustment after transdermal T gel application is unknown, especially in older men with thinner skin and slower metabolic clearance.Objectives:The objectives of the study was to determine the variability of postgel application serum T concentrations and assess whether single levels are reflective of average serum T concentrations over 24 hours (Cavg0–24).Design:This was a double-blinded, placebo-controlled randomized trial.Setting:The study was conducted at five academic centers.Participants:Forty-seven symptomatic men 65 years old or older with an average of two morning T concentration less than 275 ng/dL participated in the study.Intervention(s):Transdermal T or placebo gel was applied for 120 ± 14 days. Monthly dose adjustments were made if necessary to target serum T between 400 and 500 to 800 ng/dL.Main Outcome Measures:Variability of serum T 2 hours after the gel application on two outpatient visits and at multiple time points over 24 hours during the inpatient day was measured.Results:On-treatment T levels varied substantially on the 2 ambulatory days and over 24 hours during the inpatient day. Ambulatory 2-hour postapplication T levels did not correlate significantly with either 2-hour postapplication serum T or Cavg0–24measured during the inpatient day. Only 22.2% of men receiving T had a Cavg0–24within the target range of 500–800 ng/dL; 81.5% had a Cavg0–24within the broader 300–1000 ng/dL range.Conclusion:Large within-individual variations in serum T after T gel application render ambulatory 2-hour postapplication T level a poor indicator of average serum T on another day. Our data point out the limitations of dose adjustments based on a single postapplication serum T measurement.

To examine the association between snoring and incident cardiovascular disease (CVD).

ObjectiveTo determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia.DesignEvaluator blinded, randomised controlled trial.Setting16 clinical sites across 11 European countries, January 2016 to 31 October 2019.Participants1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls).InterventionsThe multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months.Main outcome measuresThe primary outcome was mobility disability (inability to independently walk 400 m in <15 minutes). Persistent mobility disability (inability to walk 400 m on two consecutive occasions) and changes from baseline to 24 and 36 months in physical performance, muscle strength, and appendicular lean mass were analysed as pre-planned secondary outcomes. Primary comparisons were conducted in participants with baseline SPPB scores of 3-7 (n=1205). Those with SPPB scores of 8 or 9 (n=314) were analysed separately for exploratory purposes.ResultsMean age of the 1519 participants (1088 women) was 78.9 (standard deviation 5.8) years. The average follow-up was 26.4 (SD 9.5) months. Among participants with SPPB scores of 3-7, mobility disability occurred in 283/605 (46.8%) assigned to the multicomponent intervention and 316/600 (52.7%) controls (hazard ratio 0.78, 95% confidence interval 0.67 to 0.92; P=0.005). Persistent mobility disability occurred in 127/605 (21.0%) participants assigned to the multicomponent intervention and 150/600 (25.0%) controls (0.79, 0.62 to 1.01; P=0.06). The between group difference in SPPB score was 0.8 points (95% confidence interval 0.5 to 1.1 points; P<0.001) and 1.0 point (95% confidence interval 0.5 to 1.6 points; P<0.001) in favour of the multicomponent intervention at 24 and 36 months, respectively. The decline in handgrip strength at 24 months was smaller in women assigned to the multicomponent intervention than to control (0.9 kg, 95% confidence interval 0.1 to 1.6 kg; P=0.028). Women in the multicomponent intervention arm lost 0.24 kg and 0.49 kg less appendicular lean mass than controls at 24 months (95% confidence interval 0.10 to 0.39 kg; P<0.001) and 36 months (0.26 to 0.73 kg; P<0.001), respectively. Serious adverse events occurred in 237/605 (39.2%) participants assigned to the multicomponent intervention and 216/600 (36.0%) controls (risk ratio 1.09, 95% confidence interval 0.94 to 1.26). In participants with SPPB scores of 8 or 9, mobility disability occurred in 46/155 (29.7%) in the multicomponent intervention and 38/159 (23.9%) controls (hazard ratio 1.25, 95% confidence interval 0.79 to 1.95; P=0.34).ConclusionsA multicomponent intervention was associated with a reduction in the incidence of mobility disability in older adults with physical frailty and sarcopenia and SPPB scores of 3-7. Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people.Trial registrationClinicalTrials.gov NCT02582138.

The relationship between low socioeconomic status (SES) and depressive symptoms is well described, also in older persons. Although studies have found associations between low SES and unhealthy lifestyle factors, and between unhealthy lifestyle factors and depressive symptoms, not much is known about unhealthy lifestyles as a potential explanation of socioeconomic differences in depressive symptoms in older persons.

Introduction:The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Methods:Narrative review. Results:Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urokinase-type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Conclusions:Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the future.

Introduction:The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age‐related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Methods:Narrative review. Results:Plasminogen activator inhibitor‐1 (PAI‐1) is a member of the superfamily of serine‐protease inhibitors (or serpins), and the principal inhibitor of both the tissue‐type and the urokinase‐type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI‐1 in a number of age‐related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Conclusions:Despite some controversial and unclear issues, PAI‐1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age‐related conditions in the future.

Background and aims: A fall is a common and traumatic event in the life of older persons. This study aims: 1) to explore the relationship between recent falls and measures of physical function in elders, and 2) to examine the role played by habitual physical activity in the relationship between recent falls and physical function. Methods: We used baseline data from 361 community-dwelling persons aged ≥80 years (mean age 85.9 yrs) enrolled in the “Invecchiamento e Longevità nel Sirente (ilSIRENTE)” study. Physical performance was assessed using the Short Physical Performance Battery (SPPB) and usual gait speed. Muscle strength was measured by hand grip strength. Functional status was assessed by the Basic (ADL) and Instrumental Activities of Daily Living (IADL) scales. Self-reported recent falls over the previous three months were recorded. Analyses of covariance were performed to evaluate the relationship between recent fall events and physical function measures. Results: Fifty participants (13.9%) reported at least one recent fall. Physically active participants had fewer falls and significantly higher physical function compared with sedentary subjects, regardless of recent falls. Significant interactions for physical activity were found in the relationships of usual gait speed and SPPB with recent fall history (p for interaction terms <0.01). A difference in usual gait speed and SPPB according to history of recent falls was found only in physically active subjects. Conclusions: Physical performance measures are negatively associated with recent falls in physically active, but not sedentary, participants. Physical activity is associated with better physical function, independently of recent fall history.

As evidence of the involvement of inflammation and oxidative damage in pathogenesis of age-related chronic diseases is growing, epidemiologists need to develop measures of both conditions to study their relationships in human populations. One way of searching for appropriate biomarkers is to examine correlations between different inflammatory markers and oxidative indices. We examined cross-sectional correlations between two inflammatory markers, serum C-reactive protein (CRP) and interleukin (IL)-6, and three oxidative indices, plasma levels of α-tocopherol and β-carotene, and urinary levels of 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP), in 60 individuals at high risk of cardiovascular disease. Correlations between the biomarkers were examined graphically and using the Pearson correlation coefficient. No correlation was found between plasma levels of α-tocopherol and either of the inflammatory markers. Plasma β-carotene inversely correlated with IL-6 (r=-0.46, p=0.0002) and CRP (r=-0.41, p=0.001). Although urinary F2-IsoP did not correlate with IL-6, this biomarker positively correlated with CRP (r=0.31, p=0.002). As only urinary F2-IsoP levels have been validated against known oxidative assaults, their positive association with CRP levels is interpreted as evidence of an interconnection between low-level inflammation and oxidative status. Urinary levels of F2-IsoP and serum levels of CRP represent appropriate biomarkers for future studies of inflammation and oxidative status in humans.