Frailty denotes a multidimensional syndrome that gives rise to vulnerability to stressors and leads to an increase of the age-related decline of different physiological systems and cognitive abilities. Aging-related alterations of the immune system may compromise its competence culminating in a chronic low-grade inflammation state. Thus, it has been proposed that frailty is associated with alterations in the concentration of pro-inflammatory molecules and in different lymphocyte subpopulations. To provide further support to the validity of that hypothesis, we conducted a cross-sectional study in a population of Spanish older adults (N = 259, aged 65 and over) classified according to their frailty status. Biomarkers analyzed included percentages of several lymphocyte subsets and several inflammation mediators, namely concentrations of interleukin 6 (IL6), C-reactive protein (CRP), tumor necrosis factor α (TNFα), and 75 kDa soluble TNFα receptor II (sTNF-RII). Reference ranges for the inflammation mediators were established for the first time in robust older adults. A significant increase in the CD4+/CD8+ ratio and a significant decrease in the % CD19+ cells were observed in the frail group. Progressive increases with frailty severity were obtained in all inflammatory mediator concentrations, especially notable for IL6 and sTNF-RII. Area under the receiver-operating characteristic curve obtained for sTNF-RII (0.90, 95% CI 0.85–0.94, P < 0.001) indicates a high accuracy in the predictive value of this biomarker for frailty. Although results from the current study revealed limited strength associations between frailty and the lymphocyte subsets assessed, data obtained for the inflammatory mediators provide further support to involvement of inflammaging in frailty status in older adults.

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Results obtained in the present study are consistent with the idea that frailty status in the elderly is associated with an additional degree of immune stimulation, manifested in a more intense disturbance of indoleamine 2,3-dioxygenase 1 and guanosine triphosphate cyclohydrolase I pathways than in nonfrail or prefrail older adults.

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Serum vitamin D deficiency is widespread among older adults and is a potential modifiable risk factor for frailty. Moreover, frailty has been suggested as an intermediate step in the association between low levels of vitamin D and mortality. Hence, we conducted a systematic review of the literature and meta-analysis to test the possible association of low concentrations of serum 25-hydroxyvitamin D (25(OH)D), a marker of vitamin D status, with frailty in later life. We reviewed cross-sectional or longitudinal studies evaluating populations of older adults and identifying frailty by a currently validated scale. Meta-analyses were restricted to cross-sectional data from studies using Fried’s phenotype to identify frailty. Twenty-six studies were considered in the qualitative synthesis, and thirteen studies were included in the meta-analyses. Quantitative analyses showed significant differences in the comparisons of frail (standardized mean difference (SMD)—1.31, 95% confidence interval (CI) (−2.47, −0.15), p = 0.0271) and pre-frail (SMD—0.79, 95% CI (−1.58, −0.003), p = 0.0491) subjects vs. non-frail subjects. Sensitivity analyses reduced heterogeneity, resulting in a smaller but still highly significant between-groups difference. Results obtained indicate that lower 25(OH)D levels are significantly associated with increasing frailty severity. Future challenges include interventional studies testing the possible benefits of vitamin D supplementation in older adults to prevent/palliate frailty and its associated outcomes.

Frailty has emerged as a reliable measure of the aging process. Since the early detection of frailty is crucial to prevent or even revert it, the use of biomarkers would allow an earlier and more objective identification of frail individuals. In order to improve the understanding of the biological features associated with frailty as well as to explore different biomarkers for its early identification, several genetic outcomes - mutagenicity, different types of genetic damage, and cellular repair capacity - were analysed in a population of older adults classified into frail, pre-frail and non-frail. Besides, influence of clinical parameters - nutritional status and cognitive status - was evaluated. No association of mutation rate or primary DNA damage with frailty was observed. However, DNA repair capacity showed a non-significant tendency to decrease with frailty, and persistent levels of phosphorylated H2AX, as indicative of DNA breakage, increased progressively with frailty severity. These results support the possible use of H2AX phosphorylation to provide information regarding frailty severity. Further investigation is necessary to determine the consistency of the current findings in different populations and larger sample sizes, to eventually standardize biomarkers to be used in clinics, and to fully understand the influence of cognitive impairment.

Aging is associated with a decline in the normal functioning of the immune system. Several studies described the relationship between immunological alterations, including immunosenescence and inflammation, and aging or age-related outcomes, such as sarcopenia, depression, and neurodegenerative disorders. Physical activity is known to improve muscle function and to exert a number of benefits on older adult health, including reduced risk for heart and metabolic system chronic diseases. However, the positive influence of physical activity on the immune system has not been elucidated. In order to shed light on the role of physical activity in immune responses of older individuals, a number of immunological parameters comprising % lymphocyte subsets (CD3, CD4, CD8, CD19, and CD1656) and serum levels of neopterin and tryptophan metabolism products were evaluated in peripheral blood samples of older adults performing normal (N = 170) or reduced (N = 89) physical activity. In addition, the potential influence of other clinical and epidemiological factors was also considered. Results showed that subjects with reduced physical activity displayed significantly higher levels of CD4/CD8 ratio, kynurenine/tryptophan ratio, and serum neopterin, along with lower %CD19 cells and tryptophan concentrations. Further, some immunological biomarkers were associated with cognitive impairment and functional status. These data contribute to reinforce the postulation that physical activity supports healthy aging, particularly by helping to protect the immunological system from aging-related changes.

Frailty is an emerging geriatric syndrome characterized by higher vulnerability to stressors, with an increased risk of adverse health outcomes such as mortality, morbidity, disability, hospitalization, and institutionalization. Although it is generally recognized to have a biological basis, no particular biological trait has been consistently associated to frailty status so far. In this work, epidemiological studies evaluating association of frailty status with alterations at cellular level - namely oxidative stress, genomic instability and DNA damage and repair biomarkers -were revised and compared. A total of 25 studies fulfilled inclusion/exclusion criteria and, consequently, were included in the review. Variations of oxidative stress biomarkers were often associated to frailty status in older people. On the contrary, genomic instability seems not to be linked to frailty. The only study which addressed the possible relationship between DNA repair modulations and frailty status also failed in finding association. Despite the large number of cellular alterations known to be associated with frailty, studies on this issue are still very scarce and limited to some of the possible cellular targets. The established link between DNA repair, genomic instability, and age and age-related disorders, encourage deeper investigations on this line.