The frailty index (FI) quantifies frailty as deficit accumulation. It has been adapted to employ laboratory test data (FI-Lab). Our objective was to systematically review and meta-analyse the FI-Lab’s ability to predict mortality. Secondary objectives were to review the FI-Lab’s association with adverse health outcomes and whether FI-Lab scores differed between the sexes. A systematic literature search was carried out using six online databases to identify studies that measured the FI-Lab in humans. Hazard ratios (HRs) were combined in a meta-analysis to create a pooled risk estimate for mortality. Of the 1,201 papers identified, spanning January 2010 until 11 July 2022, 38 were included. FI-Lab scores per 0.01 unit increase predicted mortality overall (HR = 1.04; 95% confidence interval (CI) = 1.03–1.05) and for studies with a mean age of 81+ years (HR = 1.04; 95% CI = 1.03–1.05). The quality of evidence for these meta-analyses are moderate and high, respectively. Further, higher FI-Lab scores were associated with more frequent adverse health outcomes. Sex differences in FI-Lab scores varied, with no consistent indication of a sex effect. The FI-Lab is associated with mortality and with a variety of adverse health outcomes. No consistent sex differences in FI-Lab scores were observed, with several studies in disagreement. Notably, these conclusions were most relevant to older (65+ years old) individuals; further evidence in younger people is needed in both clinical and population representative studies.

Chronic low-grade elevations of blood-borne cytokines/chemokines in older age tend to associate with frailty in humans. This persistent inflammation is often called "inflammageing" and likely contributes to frailty progression. Preclinical models such as ageing and/or genetically modified mice offer a unique opportunity to mechanistically study how these inflammatory mediators affect frailty. In this review, we summarize and contrast evidence relating cytokines/chemokines to frailty in humans and in mouse models of frailty. In humans and mice, higher levels of the pro-inflammatory cytokine interleukin-6 regularly increased in proportion to the degree of frailty. Evidence linking other cytokines/chemokines to frailty in humans and mice is less certain. The chemokines CXCL-10 and monocyte chemoattractant protein-1 related to frailty across both species, but evidence is limited and inconsistent. Several other cytokines/chemokines, including tumour necrosis factor-α relate to frailty in humans or in mice, but evidence to date is species- and tissue-dependent. It is important for future studies to validate common mechanistic inflammatory biomarkers of frailty between humans and mice. Achieving this goal will accelerate the search for drugs to treat frailty.

We investigated whether maladaptive, age-associated changes in heart structure and function were linked to circulating testosterone levels. Male C57BL/6 mice had a gonadectomy (GDX) or sham surgery at 4 weeks and effects of GDX on the heart were examined with echocardiography. Serum testosterone was measured with ELISA. Left ventricular (LV) mass increased with age but was smaller in GDX mice than sham at 18 months (144.0 ± 8.7 vs 118.2 ± 11.9 mg; p = 0.009). The isovolumic relaxation time (IVRT) declined with age but was prolonged in GDX mice at 18 months (10.5 ± 0.8 vs 12.5 ± 0.5 msec, p = 0.008). Ejection fraction did not change with age or GDX, but E/A ratios were lower in GDX mice than controls at 18 months (1.6 ± 0.2 vs 1.3 ± 0.1, p = 0.021). When links between serum testosterone and cardiac parameters were examined longitudinally in 18-24-month-old mice, LV mass declined with decreasing testosterone (β = 37.70, p = 0.016), however IVRT increased as testosterone decreased (β=-2.69, p = 0.036). Since longer IVRT and lower E/A ratios are signs of diastolic dysfunction, low circulating testosterone may promote or exacerbate diastolic dysfunction in older males. These findings suggest that lower testosterone directly modifies heart structure and function to promote maladaptive remodeling and diastolic dysfunction in the aging heart.

Childhood and adolescent cancer survivors are disproportionately more likely to develop cardiovascular diseases from the late effects of cardiotoxic therapies (e.g., anthracycline-based chemotherapy and chest-directed radiotherapy). Currently, dexrazoxane is the only approved drug for preventing cancer treatment-related cardiac damage. While animal models highlight the beneficial effects of exercise cancer treatment-related cardiac dysfunction, few clinical studies have been conducted. Thus, the objective of this scoping review was to explore the designs and impact of exercise-based interventions for managing cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors. Reviewers used Joanna Briggs Institute’s methodology to identify relevant literature. Then, 4616 studies were screened, and three reviewers extracted relevant data from six reports. Reviewers found that exercise interventions to prevent cancer treatment-related cardiac dysfunction in childhood and adolescent cancer survivors vary regarding frequency, intensity, time, and type of exercise intervention. Further, the review suggests that exercise promotes positive effects on managing cancer treatment-related cardiac dysfunction across numerous indices of heart health. However, the few clinical studies employing exercise interventions for childhood and adolescent cancer survivors highlight the necessity for more research in this area.

Older men with low testosterone levels are at increased risk of developing cardiac arrhythmias. We found aged mice chronically exposed to low testosterone had more arrhythmias and ventricular myocytes had prolonged repolarization, abnormal electrical activity, larger late sodium currents, and increased expression of Na_V1.8 sodium channels. Drugs that inhibit late sodium current or Na_V1.8 channels abolished abnormal electrical activity and shortened repolarization. This suggests the late sodium current may be a novel target to treat arrhythmias in older testosterone-deficient men.