Preclinical Studies on the Effects of Frailty in the Aging Heart.

ABSTRACT

Age is a major risk factor for the development of cardiovascular diseases in men and in women. However, not all people age at the same rate and those who are aging rapidly are considered frail, compared with their fit counterparts. Frailty is an important clinical challenge because those who are frail are more likely to develop and die from illnesses, including cardiovascular diseases, than fit people of the same age. This increase in susceptibility to cardiovascular diseases in older individuals might occur as the cellular and molecular mechanisms involved in the aging process facilitate structural and functional damage in the heart. Consistent with this, recent studies in murine frailty models have provided strong evidence that maladaptive cardiac remodelling in older mice is the most pronounced in mice with a high level of frailty. For example, there is evidence that ventricular hypertrophy and contractile dysfunction increase as frailty increases in aging mice. Additionally, fibrosis and slowing of conduction in the sinoatrial node and atria are proportional to the level of frailty. These modifications could predispose frail older adults to diseases like heart failure and atrial fibrillation. This preclinical work also raises the possibility that emerging interventions designed to "treat frailty" might also treat or prevent cardiovascular diseases. These findings might help to explain why frail older people are most likely to develop these disorders as they age.