Effect of aging on cellular mechanotransduction

Abstract

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, respiratory systems and skin.

Figure 1

A simplified schematic of the mechanotransduction processes. The mechanotransductive responses consist of three distinct phases: signal transduction, signal propagation, and cellular response.

Figure 2

Dysregulation of mechanotransduction in aging skeletal muscle. At rest the basal expression of mechano growth factor (MGF or IGF-IEc) and IGF-I receptor (IGF-IR) are decreased, while myostatin expression is increased. With aging, the basal phosphorylation of MAPK, Akt and p70S6k are higher, while Akt activity may be decreased. These alterations are thought to impair the ability of aged skeletal muscle to sense and respond to the mechanical stimuli, which may be associated with decreases in mechanically-induced hypertrophy. ActRIIb: activin receptor IIb.

Figure 3

Stress-induced signaling in aorta. A. Effect of aging on load-induced signaling following multi-axial stress in the aging F344BN aorta. B. Effect of aging on load-induced signaling following uni-axial stress in the aging F344BN aorta. Unfilled circles represent age-related differences (see text for details).

Figure 4

An overview of the relationship between insulin/IGF-I desensitization and Alzheimer s disease. Insulin resistance is associated with diminished activation of Shc/GRB2/MAPK and IRS/PI3K/Akt signaling, which could lead to increased Tau phosphorylation and Aβ accumulation (see text for details).