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7 Ways Your Body Ages as Your Ca2+ATPase Saps Away

What does Ca2+ATPase have to do with age-related diseases? In short: everything.

As we age, Ca2+ATPase levels decline in many tissues throughout the body, including the brain, the heart, the blood vessels, the bladder, and the skeletal muscles. Reduced Ca2+ATPase levels play a major role in many age-related diseases such as Alzheimer’s, heart failure, high blood pressure, muscle weakness and bladder problems. Here is a breakdown of how Ca2+ATPase levels figure into age-related diseases.

 

1. Brain

 

The aging brain has decreased Ca2+ATPase levels in the cortex, striatum and hippocampus. As a result of reduced Ca2+ATPase levels, intracellular calcium levels increase beyond optimal levels. This increase in brain calcium is linked to many degenerative brain diseases, including Alzheimer’s. In the brain, calcium is fundamental to the control of synaptic activity and memory formation. Properly controlled homeostasis of calcium signaling not only supports normal brain physiology but also helps the brain maintain neuronal integrity and long term cell survival.

When studied in rats, the decreased levels of Ca2+ATPase with age has been shown to reduce the total mass of the brain synaptic plasma membrane, which is responsible for protecting against degeneration (Zaidi).

 

2. Cardiac Health

 

As we age, Ca2+ATPase levels decline substantially in cardiac muscle tissue. In fact, this is a primary reason for heart failure. When the heart muscle does not have adequate Ca2+ATPase levels, it cannot relax after contraction (Feridooni).  In addition, it can’t fully contract on the next beat. The mismatch between contraction and relaxation reduces the heart’s ability to pump efficiently, ultimately resulting in heart failure.

 

3. Blood Pressure

 

Research indicates that some individuals with high blood pressure have reduced Ca2+ATPase levels, and corresponding intracellular calcium overload (Erne). Excessive intracellular calcium levels makes it hard for the blood vessels to relax. When blood vessels are constricted,  the result is high blood pressure.

 

4. Skeletal Muscle

 

Ca2+ATPase levels are significantly reduced in aging skeletal muscle.  Reduced Ca2+ATPase levels in these movement muscles lead to quicker muscle fatigue and to lower baseline strength (Narayanan).  Interestingly, the decline in Ca2+ATPase levels also affects the contraction and relaxation of the diaphragm, which compromises our ability to breathe well as we age.

Conversely, we see higher Ca2+ATPase levels during skeletal muscle growth, and can be found in increased levels during neonatal development (MacLennan).

 

5. Eyes

 

Ca2+ATPase maintains optimal calcium levels in the lenses of our eyes. Decreased Ca2+ATPase results in increased calcium levels in the lens, leading to lens opacification, the cloudiness we know as cataracts. Studies of cataract models suggest that decreases in Ca2+ATPase are concurrent with cataract development (Nagai).

 

6. Bladder Function

 

Ca2+ATPase levels are on average 40% lower in the bladders of men with bladder dysfunction as compared to men of similar age with normal bladder function. In women, reduced estrogen levels are associated with reduced bladder Ca2+ATPase levels, which corresponds with the severity of bladder dysfunction.

 

7. Sleep

 

As we age, Ca2+ATPase levels decline in the pineal gland.  Two things occur as a direct result:  The first and most immediate is reduced melatonin secretion, which is disruptive to both quality and quantity of sleep. Secondly, long term shortfalls of Ca2+ATPase levels can lead to pineal gland calcification (Krstić).

The interplay between Ca2+ATPase levels and age-related diseases is undeniable. One thing that remains reassuring in light of research that’s been conducted around this interplay is that we can prevent, or manage, age-related health problems by vigilantly managing Ca2+ATPase levels.

 

Sources:

Am J Epidemiol. 2007 Feb 1;165(3):309-18. “Biochemical evaluation of obstructive bladder dysfunction in men secondary to BPH: a preliminary report.” Levin RM, Haugaard N, Mogavero L, Leggett RE, Das AK. Urology. 1999 Feb;53(2):446-50.

Erne, Paul, et al. “Correlation of Platelet Calcium with Blood Pressure.” New England Journal of Medicine, vol. 310, no. 17, 1984, pp. 1084–1088., doi:10.1056/nejm198404263101705.

Feridooni H, Dibb K, Howlett S. “How cardiomyocyte excitation, calcium release and contraction become altered with age.” J Mol Cell Cardiol 2015 Jun;83:62-72.

Krstić R.J “Pineal calcification: its mechanism and significance.” Neural Transm Suppl. 1986;21:415-32.

MacLennanD. H.BrandlC. J.KorczakB., and  GreenN. M. (1985) “Amino-acid sequence of a Ca2+ + Mg2+-dependent ATPase from rabbit muscle sarcoplasmic reticulum, deduced from its complementary DNA sequence.” Nature pp. 316696700

Nagai, Noriaki, et al. “Comparison of the Mechanisms of Cataract Development Involving Differences in Ca2+ Regulation in Lenses among Three Hereditary Cataract Model Rats.” Biological & Pharmaceutical Bulletin, vol. 31, no. 11, 2008, pp. 1990–1995., doi:10.1248/bpb.31.1990.

Narayanan N, Jones D, Xu A, Yu J. “Effects of aging on sarcoplasmic reticulum function and contraction duration in skeletal muscles of the rat. “Am J Physiol 1996 Oct;271(4 Pt 1):C1032-40.

Zaidi, A, et al. “Age-Related Decrease in Brain Synaptic Membrane Ca2+-ATPase in F344/BNF1 Rats.” Neurobiology of Aging, vol. 19, no. 5, 1998, pp. 487–495., doi:10.1016/s0197-4580(98)00078-5.