Louis Nuvagah Forti

Dose-and gender-specific effects of resistance training on circulating levels of brain derived neurotrophic factor (BDNF) in community-dwelling older adults.

BACKGROUND BDNF is known to induce neuroplasticity and low circulating levels have been related to neuronal loss in older persons. Physical exercise is thought to trigger BDNF-induced neuroplasticity, but conflicting observations have been reported regarding the effects of resistance training on circulating BDNF in the elderly. These conflicting observations might reflect dose-and gender-specific differences. METHOD Fifty-six apparently healthy elderly (68 ± 5 years) participants were randomized to 12 weeks of resistance training (3×/week) at either high-resistance (HIGH, 8 Males, 10 Females, 2 × 10-15 repetitions at 80% 1 RM), low-resistance (LOW, 9 Males, 10 Females, 1 × 80-100 repetitions at 20% 1 RM), or mixed low-resistance (LOW+, 9 Males, 10 Females, 1 × 60 repetitions at 20% 1 RM followed by 1 × 10-20 repetitions at 40% 1 RM). Serum was collected for BDNF assay at baseline and after 12 weeks (24 h-48 h after the last training). RESULTS 12 weeks of LOW+ exercise significantly increased BDNF levels in male (from 34.9 ± 10.7 ng/mL to 42.9 ± 11.9 ng/mL, time × group interaction p=0.013), but not in female participants. No significant change was observed in HIGH or LOW, neither in male nor female subjects. CONCLUSION Our results show that only the mixed-low-resistance training program with a very high number of repetitions at a sufficiently high external resistance was able to increase circulating BDNF in older male participants. Training to volitional fatigue might be necessary to obtain optimal results. Additional studies are needed to unravel the underlying mechanisms, as well as to confirm the observed gender difference.

Effects of resistance training at different loads on inflammatory markers in young adults

PurposeSuppressing inflammaging at an early stage in life via exercise might prevent chronic diseases later in life. The aim was to investigate the influence of resistance training at different external loads on inflammatory markers in healthy young adults.MethodsSerum was collected for basal levels of cytokines (IL-1beta, IL-6, IL-8, sTNFR1, IL-1RA, IL-10 and GM-CSF) before and after 9 weeks exercise from 36 young (22 ± 2 years) healthy subjects who were randomized to three times weekly supervised resistance training at either HImax (n = 12, 1 × 10–12 repetitions at 80% 1RM), LO (n = 12, 1 × 10–12 repetitions at 40% 1RM), or LOmax (n = 12, 1 × 10–12 repetitions at 40% 1RM preceded by 60 repetitions at 20–25% 1RM) respectively.ResultsOverall, IL-8 increased (p < 0.001) and IL-6 decreased (p = 0.001) after training, but no significant time*group interaction was found (respectively, p = 0.283 and p = 0.058 for IL-8 and IL-6). When analyzed separately, IL-8 increased significantly in HImax (p = 0.022) and LOmax (p = 0.024); and IL-6 decreased significantly in LOmax (p = 0.009) and LO (p = 0.013). No significant overall time effect was observed for sTNFR1 and IL-1RA; however, in HImax sTNFR1 (p = 0.031) and IL-1RA (p = 0.014) increased significantly, but remained unchanged in LOmax and LO. IL-1beta, IL-10 and GM-CSF levels remained undetectable in most participants.ConclusionsNine weeks of resistance training—irrespective of the external load—have beneficial effects on circulating IL-8 and IL-6. In addition, training at high external load increases the anti-inflammatory cytokines sTNFR1 and IL-1RA. The results of this study show that resistance training has anti-inflammatory effects in healthy young persons and that the response of the different inflammatory mediators depends on the magnitude of the external load.

The effects of exercise on muscle strength, body composition, physical functioning and the inflammatory profile of older adults: a systematic review.

Purpose of review This systematic review reports the most recent literature regarding the effects of physical exercise on muscle strength, body composition, physical functioning and inflammation in older adults. All articles were assessed for methodological quality and where possible effect size was calculated. Recent findings Thirty-four articles were included – four involving frail, 24 healthy and five older adults with a specific disease. One reported on both frail and nonfrail patients. Several types of exercise were used: resistance training, aerobic training, combined resistance training and aerobic training and others. In frail older persons, moderate-to-large beneficial exercise effects were noted on inflammation, muscle strength and physical functioning. In healthy older persons, effects of resistance training (most frequently investigated) on inflammation or muscle strength can be influenced by the exercise modalities (intensity and rest interval between sets). Muscle strength seemed the most frequently used outcome measure, with moderate-to-large effects obtained regardless the exercise intervention studied. Similar effects were found in patients with specific diseases. Summary Exercise has moderate-to-large effects on muscle strength, body composition, physical functioning and inflammation in older adults. Future studies should focus on the influence of specific exercise modalities and target the frail population more.

Aging-associated subpopulations of human CD8+ T-lymphocytes identified by their CD28 and CD57 phenotypes.

BACKGROUND During organismal aging, human T-cells shift towards less functional phenotypes, often called senescent cells. As these cells have not been well characterized, we aimed to relate surface markers of human T-cell senescence with characteristics of in vitro cellular aging and to further characterize these cells. METHODS We identified, by flow cytometry, subpopulations of CD8+ T-cells based on CD57 and CD28 expression, and tested them for some markers of cellular senescence, apoptosis, differentiation and homing. RESULTS Elderly persons presented significantly higher proportions not only of CD28-CD57+, but also of CD28+CD57+ cells. CD28+CD57+ cells had the highest expression of p16, p21, Bcl-2, CD95, CD45RO, CCR5 and PD-1, thereby arguing in favor of a senescent phenotype. CONCLUSION Among CD8+ T-lymphocytes, CD28+CD57+ cells represent a subset with some senescent features that are distinct from the CD28-CD57+ cells.

Shifts in subsets of CD8+ T-cells as evidence of immunosenescence in patients with cancers affecting the lungs: an observational case-control study

BackgroundShifts in CD8+ T-cell subsets that are hallmarks of immunosenescence are observed in ageing and in conditions of chronic immune stimulation. Presently, there is limited documentation of such changes in lung cancer and other malignancies affecting the lungs.MethodsChanges in CD8+ T-cell subsets, based on the expression of CD28 and CD57, were analysed in patients with various forms of cancer affecting the lungs, undergoing chemotherapy and in a control group over six months, using multi-colour flow cytometry.ResultsThe differences between patients and controls, and the changes in the frequency of CD8+ T-cell subpopulations among lung cancer patients corresponded to those seen in immunosenescence: lower CD8-/CD8+ ratio, lower proportions of CD28+CD57- cells consisting of naïve and central memory cells, and higher proportions of senescent-enriched CD28-CD57+ cells among the lung cancer patients, with the stage IV lung cancer patients showing the most pronounced changes. Also observed was a tendency of chemotherapy to induce the formation of CD28+CD57+ cells, which, in line with the capacity of chemotherapy to induce the formation of senescent cells, might provide more evidence supporting CD28+CD57+ cells as senescent cells.ConclusionImmunosenescence was present before the start of the treatment; it appeared to be pronounced in patients with advanced cases of malignancies affecting the lungs, and might not be averted by chemotherapy.

Association Between Immunosenescence Phenotypes and Pre-frailty in Older Subjects: Does Cytomegalovirus Play a Role?

Frailty is highly prevalent in old age and confers an important mortality risk. Although the causes of frailty are multiple, immunosenescence (IS)-predominantly driven by cytomegalovirus (CMV)-has been implicated in its pathophysiology. Thus far, research examining the association between IS and frailty states is sparse and equivocal. On the other hand, evidence is mounting in support of the view that frailty can be reversed, especially for those in the pre-frail stage. Therefore, we aimed to clarify the impact of CMV on IS and its relevance to pre-frailty. One hundred seventy-three persons aged 80 to 99 years were enrolled. Pre-frailty was defined according to Frieds criteria. Anti-CMV IgG and serum IL-6 were measured using Architect iSystem and Luminex, respectively. T-cell phenotypes were determined using flow cytometry. The prevalence of pre-frailty was 52.6%, increased with age (p = .001), and was greater in men than women (p = .044). No relationship was found between pre-frailty and positive CMV serology. Further, CMV-seropositivity was significantly associated with less naïve cells, more memory and senescence-prone phenotypes (all p < .001). After adjusting for potential confounders, only IL-6, age and sex were predictive of pre-frailty. We conclude that the presence of pre-frailty is independent from CMV infection in very old subjects.