Keeping the clocks ticking as we age: changes in sinoatrial node gene expression and function in the ageing heart

Rose, Robert A.

doi:10.1113/expphysiol.2011.060418

Cited by 4 publications

(2 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These changes are thought to contribute to the age-dependent declines in iHR and mHR by limiting the ability of the relatively small sinoatrial node to overcome the hyperpolarizing load of the much larger surrounding atrial tissue (41,42). In addition to these mechanisms, a decrease in excitability of individual SAMs has been proposed as a potential factor that could contribute to age-dependent reductions in iHR and mHR (14,15,43). Our present data establish that aging does indeed depress the spontaneous activity of SAMs as a result of altered membrane properties.…”

Section: Discussionmentioning

confidence: 99%

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Larson

Clair

Sumner

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

118

163

View full text Add to dashboard Cite

An inexorable decline in maximum heart rate (mHR) progressively limits human aerobic capacity with advancing age. This decrease in mHR results from an age-dependent reduction in "intrinsic heart rate" (iHR), which is measured during autonomic blockade. The reduced iHR indicates, by definition, that pacemaker function of the sinoatrial node is compromised during aging. However, little is known about the properties of pacemaker myocytes in the aged sinoatrial node. Here, we show that depressed excitability of individual sinoatrial node myocytes (SAMs) contributes to reductions in heart rate with advancing age. We found that agedependent declines in mHR and iHR in ECG recordings from mice were paralleled by declines in spontaneous action potential (AP) firing rates (FRs) in patch-clamp recordings from acutely isolated SAMs. The slower FR of aged SAMs resulted from changes in the AP waveform that were limited to hyperpolarization of the maximum diastolic potential and slowing of the early part of the diastolic depolarization. These AP waveform changes were associated with cellular hypertrophy, reduced current densities for L-and T-type Ca 2+ currents and the "funny current" (I f ), and a hyperpolarizing shift in the voltage dependence of I f . The agedependent reduction in sinoatrial node function was not associated with changes in β-adrenergic responsiveness, which was preserved during aging for heart rate, SAM FR, L-and T-type Ca 2+ currents, and I f . Our results indicate that depressed excitability of individual SAMs due to altered ion channel activity contributes to the decline in mHR, and thus aerobic capacity, during normal aging. O ne of the most insidious aspects of growing older is an inevitable decline in maximum heart rate (mHR), which limits maximum aerobic capacity with advancing age (1-3). The decline in mHR proceeds at approximately the same rate for all individuals, without regard for lifestyle or physical fitness (4-8). For many otherwise healthy elderly people, it is the factor that ultimately restricts the ability to live independently (9, 10).The decrease in mHR with age results primarily from a parallel age-dependent decline in "intrinsic heart rate" (iHR) (11-13), which is measured during autonomic blockade, and thus reflects the spontaneous pacemaker activity of the sinoatrial node of the heart. Although it is known that the intact sinoatrial node from aged animals contracts more slowly (14, 15) and contains fewer pacemaker myocytes (16), little is known about the functional properties of individual myocytes from the sinoatrial node of the aged heart.Sinoatrial myocytes (SAMs) are highly specialized cells that serve a primarily electrical function as cardiac pacemakers via their production of spontaneous action potentials (APs). Sinoatrial APs are characterized by a spontaneous depolarization during diastole that drives the membrane potential to threshold, thereby triggering the subsequent AP. This "diastolic depolarization" (DD) phase of the sinoatrial AP results from the coordinated activit...

show abstract

Section: Discussionmentioning

confidence: 99%

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Larson

Clair

Sumner

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

118

163

View full text Add to dashboard Cite

show abstract

“…Interestingly, several study focusing on understanding age-dependent changes of gene expression revealed that expression of several channels are altered in the SAN and cardiac myocytes of aged animals. Perhaps counterintuitively, it was observed that in aged animals Na + , Ca 2+ , and K + channels increased their expression level in the SAN and atrial muscle [9][10][11][12].…”

Section: Ion Channels In the Aging Mosaic Of The Sinoatrial Node (San)mentioning

confidence: 98%

Ion Channels in Aging and Aging-Related Diseases

Rao¹,

Kaja²,

Gentile³

2016

Molecular Mechanisms of the Aging Process and Rejuvenation

View full text Add to dashboard Cite

Abstract"ging in humans is the decline over function of time of biological processes that include the capacity to grow, to reproduce, to interact, and to adapt, resulting in progressive organ malfunctions, illnesses, and ultimately death. "s the average life expectancy is estimated to be above years for about % of the world's population by , understanding the causes of and designing treatments for aging-related disease is a compelling priority. "lthough every organ and tissue undergoes the process of aging, it appears that only few pathogeneses are typically detected with high frequency in elderly individuals. These include cardiovascular disease, neurodegeneration, vision loss, and cancer. Therefore, aging could be measured by monitoring the occurrence and progression of these diseases. However, each of these medical conditions alone is not a good marker for aging as elder patients present comorbid chronic conditions. In addition, treatment of one disease does not significantly prolong life expectancy. Therefore, it appears that a possible antiaging therapeutic strategy should consider simultaneous treatment of several diseases or move toward identification of a common target among the biological processes involved in aging. In this chapter, we will discuss some of the basic concepts of the role of ion channels in aging and will present an overview of the function of ion channels in some of the most common aging-related diseases.

show abstract

Modeling Heart Pacemaker Tissue by a Network of Stochastic Oscillatory Cellular Automata

Makowiec

2013

Unconventional Computation and Natural Computation

View full text Add to dashboard Cite

Keeping the clocks ticking as we age: changes in sinoatrial node gene expression and function in the ageing heart

Cited by 4 publications

References 5 publications

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Depressed pacemaker activity of sinoatrial node myocytes contributes to the age-dependent decline in maximum heart rate

Ion Channels in Aging and Aging-Related Diseases

Modeling Heart Pacemaker Tissue by a Network of Stochastic Oscillatory Cellular Automata

Contact Info

Product

Resources

About