Age-Related Frailty, a Case of All Too Little Prevention
One of the interesting points made in today's open access review paper is that there is a lack of research into the early manifestations and prevention of frailty. According to the authors, it was only recently the case that the research community established that meaningful levels of pre-frailty exist in middle-age. Further, while it is well established that resistance exercise is the best intervention for the treatment of pre-frailty and frailty at this time, the data is far less comprehensive when looking only at the question of early prevention in middle-age than, say, the evidence for statin use in atherosclerosis or other widely used pharmacological therapies.
A number of the small molecule therapies under development in the longevity industry are targeting components of frailty, particularly sarcopenia, the loss of muscle mass and strength. Some of these may be exploiting one or more of the many mechanisms making up the beneficial response to exercise, and quite likely so if the small molecules arose from unbiased screening exercises. It remains to be seen as to whether the treatments will match the benefits produced by resistance exercise. Calorie restriction mimetics perform less capably than the practice of calorie restriction, and we should probably expect the same to be true for exercise mimetics versus exercise.
While this review identified multicomponent and resistance exercise as the most effective interventions for preventing or reversing pre-frailty/frailty in 40-65-year-olds, significant evidence gaps, limited methodologies, and risk of bias were present in the literature. Previous reviews have demonstrated the benefits of resistance training in preventing or reversing pre-frailty and frailty in older adults. However, we found only one study which independently evaluated resistance training for middle-aged adults. In most instances resistance training was incorporated into multicomponent exercise programs (MEPs) making it difficult to understand the effectiveness of these interventions beyond standalone resistance training. This trend may stem from World Health Organisation (WHO) recommendations favouring multicomponent exercise for older adults. However, it's unclear if these complex interventions add sufficient benefit over resistance training alone.
Low-intensity and dynamic exercises have been shown to be less effective for preventing or reversing pre-frailty than other forms of exercise, though they do improve balance, an early frailty predictor. While these exercises benefit older adults, especially in balance, resistance training also enhances balance and offers additional benefits such as increased bone density. Nonetheless, the practicality of integrating low-intensity exercises like walking into daily routines for balance improvement shouldn't be underestimated.
There was insufficient evidence to recommend flavonoid supplementation or metformin prescription for preventing or reversing pre-frailty/frailty in middle-aged individuals. These findings are not surprising as similarly, in older adults, evidence is sparse or emerging. Unlike these less supported interventions, nutritional approaches like protein and/or creatine supplementation have strong evidence for frailty prevention/reversal in older adults. Specifically, in older adults, protein supplementation in conjunction with resistance training exercise is more effective than either intervention alone. Yet, in none of these studies was protein supplementation or any nutritional intervention included in conjunction with exercise. Considering the established benefits in older adults, future research in this younger age group is indicated.
The small number of studies in this review underscores the emerging nature of evidence for interventions targeting frailty in middle-aged adults. Notably, the high levels of detectable pre-frailty in middle age is an only recently discovered phenomenon, highlighting a research gap in this age range. The infrequent use of terms like 'pre-frailty' and 'frailty' in 40-65-year-olds suggests missed opportunities for research. Although previous studies have focused on related concepts such as functional decline or sarcopenia in older adults, their relevance to this younger group remains underexplored.