Physical activity and exercise: Strategies to manage frailty

Abstract

Frailty, a consequence of the interaction of the aging process and certain chronic diseases, compromises functional outcomes in the elderly and substantially increases their risk for developing disabilities and other adverse outcomes. Frailty follows from the combination of several impaired physiological mechanisms affecting multiple organs and systems. And, though frailty and sarcopenia are related, they are two different conditions. Thus, strategies to preserve or improve functional status should consider systemic function in addition to muscle conditioning. Physical activity/exercise is considered one of the main strategies to counteract frailty-related physical impairment in the elderly. Exercise reduces age-related oxidative damage and chronic inflammation, increases autophagy, and improves mitochondrial function, myokine profile, insulin-like growth factor-1 (IGF-1) signaling pathway, and insulin sensitivity. Exercise interventions target resistance (strength and power), aerobic, balance, and flexibility work. Each type improves different aspects of physical functioning, though they could be combined according to need and prescribed as a multicomponent intervention. Therefore, exercise intervention programs should be prescribed based on an individual's physical functioning and adapted to the ensuing response.

Keywords: Aging; Exercise; Frailty; Multicomponent intervention; Oxidative stress; Physical activity.

Fig. 1

Three different trajectories of intrinsic capacity along the lifetime: Accelerated aging, usual aging, and successful/healthy aging. Trajectories are suitable for intervention, acting on the rate of decrease in intrinsic capacity.

Fig. 2

Shortening of intrinsic capacity and functional reserve leading to frailty and, if no intervention, to disability and death. As these shortages progress, the likelihood of reversing functional impairment decreases. When the threshold for disability is crossed, the possibility of restoring robustness is uncertain.

Fig. 3

The spectrum of intrinsic capacity from the perspectives of organ and systemic level, and their clinical manifestations. In the first stages, there are changes in isolated organs that can still be reversed and do not impact function due to a high functional reserve. As the condition progresses, other organs start to deteriorate, due to the aging processes or to the accumulation of chronic diseases sharing similar mechanisms of damage. At this stage frailty status appears: there is still enough functional reserve to maintain functional autonomy, although some deterioration in performance-based tasks can be observed if carefully assessed. If the condition continues progressing, functional reserve is depleted and disability takes hold, with few chances for recovery.

Fig. 4

Aging together with increase in oxidative damage and chronic inflammation represent three interrelated age-dependent processes that provide a background prone to organic systems dysfunction and age-related chronic diseases. The interaction between age-related chronic diseases, aging process, oxidative stress, and inflammation may lead to multisystem dysfunction and frailty phenotype in the elderly.

Fig. 5

Aging process is associated with increased reactive oxygen species (ROS) and inflammation resulting in muscle dysfunction. Decreased levels of insulin-like growth factor (IGF-1) are related to aging with the subsequent diminished protein synthesis and muscle growth via phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway. Exercise may exert potent anti-inflammatory and anti-oxidative stress (i.e., through nuclear erythroid-2 like factor-2 (Nrf-2) activation) effects and consequently improve muscle function. In addition, exercise increases protein synthesis via activation of IGF-1 pathway and target myokines reducing protein degradation. An increased signaling of the transcription factor peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is also induced by exercise, improving mitochondrial function and reducing inflammation mediated by nuclear factor κB (NF-κB).

Fig. 6

Physical activity/exercise training may influence the outcome of the aging process by modulating key signaling pathways. Exercising results in reduced age-related oxidative damage, reduced chronic inflammation, increased autophagy, improved mitochondrial function, improved myokine profile, augmented insulin-like growth factor-1 (IGF-1) signaling, and insulin sensitivity. These actions promote beneficial effects on skeletal muscle (muscle mass, strength, and function) but also at systemic level, inducing improvements in function of cardiovascular, respiratory and metabolic systems. Exercise-induced improvements in muscle function as well as systemic benefits and age-related chronic diseases alleviation are all related to the improvements in physical function and frailty improvement by exercise/physical activity.

Fig. 7

Distribution of the type of exercises in a standard training session according to patient frailty status. Intensity should generally increase as the frailty status improves, although High Interval Intensity Training-HIIT can be used also in frail patients.