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Background and purpose Although combining classical resistance (RT) and power training (PT) might be an efficient strategy to achieve optimal enhancements in body composition and physical function in older adults, the most effective approach to combine these different types of exercise training is still unknown. Periodization, an organizational model that refers to a succession of cycle that will vary in exercise intensity and/or volume to allow for the training stimulus to remain biologically challenging and effective, may represent an interesting approach. Among the different types of periodization, daily undulating periodization (DUP) has attracted considerable attention given its superiority in comparison to nonperiodized (NP) RT programs to elicit neuromuscular improvements in young adults. However, whether a DUP program combining PT and traditional RT can produce similar or greater improvements in body composition and physical function in older adults than a NP RT program has not yet been established. Therefore, the present study compared the effects of a DUP and NP programs on body composition and physical function in healthy community-dwelling older women. Methods Forty-two older women (60–79 years) were randomized into one of the three experimental groups: NP, DUP, and control group (CG). Body composition and physical function were assessed at baseline and after the intervention. The sessions of exercises were performed twice a week over 22 weeks. In NP, the two exercise sessions were based on three sets of 8–10 repetitions at a “difficult” intensity (i.e., 5–6) prescribed based on the Rating of Perceived Exertion (RPE) scale. In DUP, the first session was based on PT (three sets of 8–10 repetitions at a “moderate” intensity, i.e., 3, performed as fast as possible), while the second session was similar to the NP. Results There were no significant changes in body composition in any of the groups. Relative to baseline, participants assigned to NP showed significant improvements in countermovement jump (+55.7%), timed “Up and Go” (TUG) test (−43.2%, faster), walking speed (+12.0%), and one-leg-stand (+154.5%). In contrast, DUP only improved TUG performance (−53.2%, faster). Conclusion NP and DUP improved physical function in community-dwelling older women, with greater improvements in physical parameters only observed after NP.

Cardiovascular disease is highly prevalent among older adults and poses a huge burden on morbidity, disability, and mortality. The age-related increased vulnerability of the cardiovascular system towards stressors is a pathophysiological trait of cardiovascular disease. This has been associated with a progressive deterioration of blood vessels and decline in heart function during aging. Cardiomyocytes rely mostly on oxidative metabolism for deploying their activities and mitochondrial metabolism is crucial to this purpose. Dysmorphic, inefficient, and oxidant-producing mitochondria have been identified in aged cardiomyocytes in association with cardiac structural and functional alterations. These aberrant organelles are thought to arise from inefficient mitochondrial quality control, which has therefore been place in the spotlight as a relevant mechanism of cardiac aging. As a result of alterations in mitochondrial quality control and redox dyshomeostasis, mitochondrial damage accumulates and contributes to cardiac frailty. Herein, we discuss the contribution of defective mitochondrial quality control pathways to cardiac frailty. Emerging findings pointing towards the exploitation of these pathways as therapeutic targets against cardiac aging and cardiovascular disease will also be illustrated.

The present study included two related investigations that explored the acute and chronic effects of high-speed resistance training (HSRT) on blood pressure (BP) in older adults.The first study involved a randomized crossover study that compared the acute effects of traditional resistance exercise (TRT) and high-speed resistance training (HSRT) on hemodynamic parameters in frail older adults. Sixteen institutionalized frail older adults were recruited. BP was recorded before, over 1 h, and 24 h after the end of the experimental session. Participants performed 4 resistance exercises involving 4-8 sets with 4-10 repetitions at moderate intensity. The second study was a systematic review and meta-analysis of experimental studies that investigated the acute and chronic effects of HSRT on BP in older adults. Crossover, quasi-experimental, and randomized controlled trials that examined the effects of HSRT on BP in people aged 60+ years as a primary or secondary outcome were included. Studies were retrieved from MEDLINE, SPORTDiscuss, CINAHL, SCOPUS and AgeLine databases from inception through December 31, 2021. The risk of bias was evaluated using the Newcastle - Ottawa Quality Assessment Scale (NOS). A pooled effect size was calculated based on standard mean differences (SMD).In study 1, we observed that both TRT and HSRT caused post-exercise hypotension (PEH). However, systolic BP (SBP) was significantly lowered for up to 60 min after TRT, while it was only reduced 30 and 50 min after HSRT. There was no difference in SBP between resistance exercise protocols. A reduction in mean arterial pressure was only observed after TRT. In study 2, 1114 articles were identified, and 8 were included in the meta-analysis. Pooled analyses indicated that HSRT did not cause significant PEH. However, a significant reduction in SBP was observed after HSRT programs in comparison to controls (SMD = 0.61, P = 0.009) and baseline values (SMD = 2.03, P = 0.04).In study one, we observed that both TRT and HSRT caused systolic PEH in comparison to baseline in frail older adults. However, specific patterns were observed according to each type of RT. Indeed, a longer PEH in comparison to baseline was observed after TRT, whereas HSRT had greater reductions in comparison to CS. In addition, TRT had exclusive reductions in MAP. These results were not supported by our meta-analysis, given that no significant effects of an acute session of HSRT on office and ambulatorial BP were observed. On the other hand, our findings suggest that HSRT might significantly reduce SBP in older adults.

Aim The present study investigated whether hypertension, blood pressure, and antihypertensive therapy were associated with frailty status in community-dwelling older adults. In addition, we tested whether such associations were consistent across different frailty instruments. Material and methods Two-hundred older adults were enrolled in the study. Participant frailty status was determined according to a modified physical frailty phenotype (mFP), the FRAIL scale, and the Study of Osteoporotic Fracture (SOF) index. Blood pressure was assessed three times, in three different days, and mean values were used in the final analysis. Information pertaining to disease conditions and antihypertensive therapy were collected by two researchers through self-report and careful review of medical charts. Results No significant differences in hemodynamic parameters, hypertension diagnosis, and antihypertensive therapy were observed across frailty statuses, regardless of the frailty assessment tool used. Conclusion Findings of the present study indicate that hypertension, blood pressure levels and antihypertensive medication were not cross-sectionally associated with frailty status in cognitively preserved community-dwelling older adults with low prevalence of comorbidities, regardless of the tool used for frailty identification.

Publisher's version (útgefin grein), Background:The ongoing “Sarcopenia and Physical fRailty IN older people: multi-componenT Treatment stra-tegies (SPRINTT)” randomized controlled trial (RCT) is testing the efficacy of a multicomponent intervention inthe prevention of mobility disability in older adults with physical frailty & sarcopenia (PF&S). Here, we describethe procedures followed for PF&S case finding and screening of candidate participants for the SPRINTT RCT. Wealso illustrate the main demographic and clinical characteristics of eligible screenees.Methods:The identification of PF&S was based on the co-occurrence of three defining elements: (1) reducedphysical performance (defined as a score on the Short Physical Performance Battery between 3 and 9); (2) lowmuscle mass according to the criteria released by the Foundation for the National Institutes of Health; and (3)absence of mobility disability (defined as ability to complete the 400-m walk test in 15 min). SPRINTT wasadvertised through a variety of means. Site-specific case finding strategies were developed to accommodate thevariability across centers in catchment area characteristics and access to the target population. A quick “parti-cipant profiling” questionnaire was devised to facilitate PF&S case finding.Results:During approximately 22 months, 12,358 prescreening interviews were completed in 17 SPRINTT sitesresulting in 6710 clinic screening visits. Eventually, 1566 candidates were found to be eligible for participatingin the SPRINTT RCT. Eligible screenees showed substantial physical function impairment and comorbidityburden. In most centers, project advertisement through mass media was the most rewarding case findingstrategy.Conclusion:PF&S case finding in the community is a challenging, but feasible task. Although largely autonomousin daily life activities, older adults with PF&S suffer from significant functional impairment and comorbidity.This subset of the older population is therefore at high risk for disability and other negative health-relatedevents. Key strategies to consider for successfully intercepting at-risk older adults should focus on mass com-munication methods., The present work was funded by a grant from the InnovativeMedicines Initiative - Joint Undertaking (IMI-JU 115621). The workwas also partly supported by the nonprofit research foundation “CentroStudi Achille e Linda Lorenzon” and by intramural research grants fromthe Università Cattolica del Sacro Cuore (D3.2 2013 and D3.2 2015).The authors thank all the participants and the staff involved in thetrial for the enthusiastic participation and dedication.

Background Cardiac structure and function change with age. The higher prevalence of left ventricular hypertrophy (LVH) with concentric remodeling is indicative of a typical geometric pattern of aging associated with a higher cardiovascular (CV) risk and diseases. The recent associations found between low left ventricular and skeletal mass in older patients with frailty and sarcopenia have raised great interest in investigating cardiac characteristics and determinants of left ventricular mass (LVM) in this population. Design Cross-sectional study. Methods We evaluated 100 sarcopenic and physically frail outpatients, 33 men (M), 67 women (F), aged ≥70 years (mean age 79 ± 5) and enrolled in the Parma site of European multicenter SPRINTT population. Results All male and female participants showed LVH, assessed as indexed LVM to body surface area (LVM/BSA) (M = 128 ± 39 g/m2; F = 104 ± 26 g/m2), and were more prone to have concentric geometry, as demonstrated by relative wall thickness value (0.41 in both sexes). After backward regression analysis, including covariates such as age, sex, office or ABPM systolic blood pressure (SBP), heart rate, BSA, use of β blockers, ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, diuretics, physical activity, hemoglobin level, and Mini Mental State examination - the most powerful determinants of LVM were clinical SBP (β = 1.51 ± 0.31, p = 0.0005), BSA (β = 165.9 ± 41.4, p = 0.0001), while less powerful determinants were 24 h, daily and nightly SBP (p = 0.02, p = 0.002, p = 0.004 respectively). Conclusions Older sarcopenic and physically frail patients showed LVH with a tendency towards concentric geometry. The main determinant of LVM was SBP, highlighting the key role that hemodynamic condition plays in determining LVH in this population.

Mitochondrial dysfunction is involved in the loss of muscle featuring both aging and cancer cachexia (CC). Whether mitochondrial quality control (MQC) is altered in skeletal myocytes of old patients with CC is unclear. The present investigation therefore sought to preliminarily characterize MQC pathways in muscle of old gastric cancer patients with cachexia. The study followed a case-control cross-sectional design. Intraoperative biopsies of the rectus abdominis muscle were obtained from 18 patients with gastric adenocarcinoma (nine with CC and nine non-cachectic) and nine controls, and assayed for the expression of a set of MQC mediators. The mitofusin 2 expression was reduced in cancer patients compared with controls, independent of CC. Fission protein 1 was instead up-regulated in CC patients relative to the other groups. The mitophagy regulators PTEN-induced putative kinase 1 and Parkin were both down-regulated in cancer patients compared with controls. The ratio between the protein content of the lipidated and non-lipidated forms of microtubule-associated protein 1 light chain 3B was lower in CC patients relative to controls and non-cachectic cancer patients. Finally, the expression of autophagy-associated protein 7, lysosome-associated membrane protein 2, peroxisome proliferator-activated receptor-γ coactivator-1α, and mitochondrial transcription factor A was unvarying among groups. Collectively, our findings indicate that, in old patients with gastric cancer, cachexia is associated with derangements of the muscular MQC axis at several checkpoints: mitochondrial dynamics, mitochondrial tagging for disposal, and mitophagy signaling. Further investigations are needed to corroborate these preliminary findings and determine whether MQC pathways may become target for future interventions.

Background The construct of physical frailty and sarcopenia (PF&S) identifies an age-related pre-disability condition defined by reduced physical performance and low muscle mass. Whether PF&S is characterized by perturbations of the cytokine network is presently unclear. Furthermore, the existence of gender-specific inflammatory profiles of PF&S is unknown. This study was designed to explore the association between a large panel of inflammatory biomolecules and PF&S in older adults through a multivariate statistical approach. Gender-specific inflammatory patterns were also explored. Methods One-hundred community-dwellers aged 70 years and older with PF&S and 100 non-sarcopenic, non-frail controls (nonPF&S) were enrolled. A panel of 30 circulating inflammatory biomarkers was assayed. Partial least squares discriminant analysis (PLS-DA) was employed to explore the relationship between inflammatory molecules and PF&S. Separate PLS-DA models were built for the whole sample and the two genders. Double cross-validation procedures were used to validate the predictive ability of PLS-DA models. Results The optimal complexity of the PLS-DA model built on the whole sample was found to be four latent variables. The proportion of correct classification was 75.6 ± 1.3% (82.3 ± 1.6% for enrollees with PF&S and 68.7 ± 2.5% for nonPF&S controls). The inflammatory profile of people with PF&S was defined by higher levels of P-selectin, C-reactive protein (CRP), and interferon γ-induced protein 10. NonPF&S participants were characterized by higher levels of myeloperoxidase (MPO), interleukin (IL) 8, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein 1-α, platelet-derived growth factor (PDGF) BB. Gender-specific PLS-DA allowed identifying a “core” inflammatory signature of PF&S, composed by higher levels of CRP, and lower concentrations of MPO, IL8, MCP-1, and PDGF-BB, with peculiar patterns of relationships for men and women. Conclusions A core inflammatory profile was identified in people with PF&S with a gender-specific signature. The dissection of the PF&S “cytokinome” will provide novel insights into the role played by inflammation in the disabling cascade and allow designing personalized treatment strategies.

Background Muscle mass and strength ineluctably decline with advancing age. Yet, the impact of ethnicity on the pattern of changes and their magnitude is unclear. The aims of the present study were to analyze age- and gender-specific changes in measures of muscle mass and strength among community-living persons and to identify differences between Caucasian and Asian participants. Methods The Italian survey (“Longevity Check-up”), conducted during Milan EXPO 2015, consisted of a population assessment aimed at evaluating the prevalence of specific health metrics in persons outside of a conventional research setting (n = 1924), with a special focus on muscle mass and strength. The Taiwanese survey used the first-wave sampling from the I-Lan Longitudinal Aging Study (ILAS) collected from August 2011 to August 2013 (n = 1839). ILAS was designed to explore the interrelationship between sarcopenia and frailty in community-dwelling older people in Taiwan. In both studies, muscle mass was estimated by measuring the calf circumference (CC), whereas muscle strength was assessed by handgrip strength testing. Results The mean age of the 1924 Italian participants was 62.5 years (standard deviation 8.3, range from 50 to 98 years), of whom 1031 (53.6%) were women. Similarly, the mean age of the Taiwanese sample was 63.9 years (standard deviation 9.3, range from 50 to 92 years), with 966 (52.5%) women. CC declined with age in both genders and was significantly greater among Italian participants compared with Taiwanese people in all age groups. A similar effect of age was observed for muscle strength. As for CC, muscle strength was significantly greater among Italian persons relative to Taiwanese participants. Conclusion Muscle mass and strength declined with age in both ethnic groups. Caucasians showed greater muscle mass and performed better than their Asian counterparts. However, the age at which declines began to appear and the rate of decline during aging were comparable between the two populations.

Background and aim Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder in old age. Neurotoxicity of dopaminergic neurons triggered by aggregation of misfolded α-synuclein is a major pathogenic trait of PD. However, growing evidence indicates that peripheral processes, including metabolic changes, may precede and contribute to neurodegeneration. The present study was undertaken to identify a metabolic signature of PD through the quantification of serum amino acids and derivatives. Participants and methods Twenty older adults with PD (11 men and 9 women; mean age 73.1 ± 10.2 years) and 30 age-matched controls (14 men and 16 women; mean age 74.6 ± 4.3 years) were enrolled. A panel of 37 serum amino acids and derivatives was assessed by ultra-performance liquid chromatography/mass spectrometry. Partial least squares − discriminant analysis (PLS-DA) followed by double cross-validation was used to characterize the relationship between amino acid profiles and PD. Results The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classifications was 99.3 ± 2.5% for participants with PD and 94.7 ± 3.0% for non-PD controls. Higher levels of β-amino butyric acid, cystine, ornithine, phosphoethanolamine, and proline defined the circulating amino acid profile of older people with PD. Controls were characterized by higher concentrations of 3-methyl-histidine, citrulline, and serine. Conclusion Our findings indicate the existence of a distinct metabotype in older persons with PD. Future studies will have to establish whether changes in amino acid metabolism are involved in the pathogenesis of PD. This knowledge may be harnessed to identify novel disease biomarkers as well as new targets for interventions.

Frailty encompasses several domains (i.e., metabolic, physical, cognitive). The multisystem derangements underlying frailty pathophysiology, its phenotypic heterogeneity, and the fluctuations of individuals across severity states have hampered a comprehensive appraisal of the condition. Circulating biomarkers emerged as an alleged tool for capturing this complexity and, as proxies for organismal metabolic changes, may hold the advantages of: 1) supporting diagnosis, 2) tracking the progression, 3) assisting healthcare professionals in clinical and therapeutic decision-making, and 4) verifying the efficacy of an intervention before measurable clinical manifestations occur. Among available analytical tools, metabolomics are able to identify and quantify the (ideally) whole repertoire of small molecules in biological matrices (i.e., cells, tissues, and biological fluids). Results of metabolomics analysis may define the final output of genome-environment interactions at the individual level. This entire collection of metabolites is called “metabolome” and is highly dynamic. Here, we discuss how monitoring the dynamics of metabolic profiles may provide a read-out of the environmental and clinical disturbances affecting cell homeostasis in frailty-associated conditions.

Background: The C-terminal agrin fragment (CAF), a circulating byproduct of neuromuscular junction disassembly, has been proposed as a possible biomarker for sarcopenia. However, its validity in "real-world", multimorbid older persons is currently unknown. The present study was undertaken to verify if serum CAF levels were associated with sarcopenia in a population of old and very old persons living in the community. Methods: Data were from the ilSIRENTE Aging and Longevity Study, a prospective cohort study conducted in all persons aged 80years and older residing in the Sirente geographic area (Italy; n=332). The identification of sarcopenia was based on the criteria elaborated by the European Working Group on Sarcopenia in Older People (EWGSOP). Serum levels of CAF were determined using a commercial ELISA kit. Results: Sarcopenia was identified in 101 participants (30.8%). Serum levels of CAF were significantly higher in older adults with sarcopenia compared with non-sarcopenic participants (96.99±5.40pmol/L vs. 76.54±2.15pmol/L; p

Physical exercise is the most effective intervention against sarcopenia of aging; however, the cellular and molecular mechanisms mediating training-induced adaptations are not yet completely understood. Furthermore, it is unclear whether exercise training initiated late in life affects myocyte anabolic signaling in a dose-dependent manner. Hence, we sought to investigate the effects of treadmill exercise and training frequency on anabolic pathways, including insulin signaling, in the skeletal muscle of old rats. Aged (14-16-month-old) male Wistar rats were trained on a treadmill for 3 (EX3) or 5 days/week (EX5) during 8 weeks and compared with age-matched sedentary controls (SED). Four-month-old rats were used as young controls (YC). Protein expression levels of insulin receptor (IR), insulin receptor substrate 1 (IRS-1), activated (phosphorylated) mammalian target of rapamycin (p-mTOR) and glucose transporter GLUT4 were determined in quadriceps muscle extracts via immunoblotting. Mitochondrial cytochrome c oxidase (COX) activity was assessed by histochemical staining, while electron microscopy was employed to quantify the sarcomere volume (V(src)). Body weight (BW) increased, whereas muscle weight (MW) and V(src) decreased with age. EX5, but not EX3 increased MW and V(src), without affecting BW. The expression of IR and GLUT4 was higher in SED rats relative to the YC group. Conversely, protein levels of IRS-1 and p-mTOR as well as COX activity were reduced in advanced age. Compared with SED rats, EX3 animals displayed reduced IR expression and increased IRS-1 levels and COX activity. The expression of GLUT 4 and p-mTOR was unaffected by EX3. EX5 up-regulated IRS-1 and p-mTOR expression and COX activity, while decreasing GLUT4 levels, with no effect on IR expression. In summary, substantial impairments in muscle anabolic pathways, including insulin signaling, were detected in aged sedentary rats. These changes were ameliorated by exercise training, concomitant with improvements in muscle trophism. Benefits were more evident in rats trained for 5 days/week, suggesting that physical exercise initiated late in life affects anabolic signaling in a dose-dependent manner.