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Review
. 2012 Jun 1;11(11):2092-9.
doi: 10.4161/cc.20317. Epub 2012 Jun 1.

Autophagy and cardiovascular aging: lesson learned from rapamycin

Sreejayan Nair  1 , Jun Ren
Affiliations
Review

Autophagy and cardiovascular aging: lesson learned from rapamycin

Sreejayan Nair et al. Cell Cycle. .

Abstract

The biological aging process is commonly associated with increased risk of cardiovascular diseases. Several theories have been put forward for aging-associated deterioration in ventricular function, including attenuation of growth hormone (insulin-like growth factors and insulin) signaling, loss of DNA replication and repair, histone acetylation and accumulation of reactive oxygen species. Recent evidence has depicted a rather unique role of autophagy as another important pathway in the regulation of longevity and senescence. Autophagy is a predominant cytoprotective (rather than self-destructive) process. It carries a prominent role in determination of lifespan. Reduced autophagy has been associated with aging, leading to accumulation of dysfunctional or damaged proteins and organelles. To the contrary, measures such as caloric restriction and exercise may promote autophagy to delay aging and associated comorbidities. Stimulation of autophagy using rapamycin may represent a novel strategy to prolong lifespan and combat aging-associated diseases. Rapamycin regulates autophagy through inhibition of the nutrient-sensing molecule mammalian target of rapamycin (mTOR). Inhibition of mTOR through rapamycin and caloric restriction promotes longevity. The purpose of this review is to recapitulate some of the recent advances in an effort to better understand the interplay between rapamycin-induced autophagy and decelerating cardiovascular aging.

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Figures

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Figure 1. Stages involved in the formation of autolysosome from phagophore for various cellular components.
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Figure 2. Signaling pathways regulating the activity of mTORC1. Growth factor (such as insulin and IGF1) stimulation activates Akt which inactivates TSC2 via phosphorylation leading to the conversion of Rheb-GTP to Reb-GD preventing inhibition of mTORC1. On the other hand, low levels of ATP can result in the activation of AMPK which can inhibit mTORC1. Activated mTORC1 can induce translation of mRNA via the phosphorylation of 4E-BP1 and p70S6 kinase. mTORC1 also results in suppression of autophagy.
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