The Intersection Between Aging and Cardiovascular Disease
Abstract/Introduction
The average lifespan of people is increasing
The leading cause of death for people 65+ is cardiovascular disease (CVD)
There is a need to find the link between the genetic pathways in aging and their role in affecting cardiovascular aging
Provides an overview of some of the key genes involved in aging/lifespan
This will account for roughly 40% of all death in this age group
Aging on the heart and a new view of CVD
The longevity genes and CVD
Discussion Series
Aging cardiovascular tissue exemplified by alterations such as muscle growth, altered diastolic function, increased arterial stiffness, and impaired endothelial function.
mouse and rat studies have been done to track the hypertrophy of the heart
Another example is a DECREASE in both the max heart rate and variability in heart rate
Decreased elasticity reduces blood flow and less responsive to stress
Cardiomycocytes that are dying release components that can affect neighboring cells and produce a cascade affect
Cardiomyocyte regeneration is a key indicator to assess aging
A calorie restricted (CR) diet combined with exercise led to increased lifespan
In mammals CR diets provided higher protection from CVD
CR triggers "longevity regulatory" pathways including IGF-1, AMPK and many more
SIR2
Sirloins are enzymes that functions NAD+ dependent deacetylases and ribosyltransferases
helps regulate DNA damage repair, cell cycle, and metabolism
IGF-1/GH
Too much IGF-1 led to death and heart failure
Forehead transcription factors (FOXO)
Regulate the expression of genes involved in cell growth, differentiation and longevity
Clock 1
biosynthesis of coenzyme Q the Electron transporter of respiration
AMPK
glucose and lipid metabolism
p66shc
modulates mitochondrial ROS
catalase
H2O2 to water and oxygen
Pituitary transcription factor
klotho
rapamycin
BubR1
First ( mitochondrial disfunction)
Second (growth factors)
Third (mitochondria and cardio agin)
Fourth (telomere attrition)
Fifth ( FOXOs/sirtuins in vascular agin)
Sixth ( angiogenesis impairment and endothelial dysfunction)
Final (nonmamallian models of cardio aging)
Reference: North BJ, Sinclair DA. 2012. The Intersection Between Aging and Cardiovascular Disease. Circulation Research. 110(8):1097–1108. doi:10.1161/circresaha.111.246876.