SOTA: Cardiovascular Aging: A Disease or Not a Disease

“Inside every old person is a young person wondering what happened.” So, what is aging? Aging is a manifestation
of progressive, time-dependent failure ofmolecularmechanismsthat create disorder within a systemof DNA
and its environment (nuclear, cytosolic, tissue, organ, organism, other organisms, society, terra firma, atmosphere,
universe). Continuous signaling, transmitted with different kinetics across each of these environments,
confers a “mutual enslavement” that creates ordered functions among the componentswithin the system. Accrual
of this molecular disorder over time, i.e. during aging, causes progressive changes in the structure and function
of the heart and arteries that are quite similar in humans, non-human primates, rabbits and rats that compromise
cardiovascular reserve function, and confer a marked risk for incident cardiovascular disease. Nearly all aspects of
signaling within the DNA environment system within the heart and arteries become disordered with advancing
age: Signals change, as does sensing of the signals, transmission of signals and responses to signals, impaired cell
renewal, changes in the proteome due to alterations in genomic transcription, mRNA translation, and
proteostasis. The density of some molecules becomes reduced, and post-translational modifications, e.g. oxidation
and nitration phosphorylation, lead to alteredmisfolding and disorderedmolecular interactions. The stoichiometry
and kinetics of enzymatic and those reactions which underlie crucial cardiac and vascular cell functions
and robust reserve mechanisms that remove damaged organelles and proteins deteriorate. The CV cells generate
an inflammatory defense in an attempt to limit the molecular disorder. The resultant proinflammatory milieu is
not executed by “professional” inflammatory cells (i.e.white blood cells), however, but by activation of renin–angiotensin–
aldosterone endothelin signaling cascades that leads to endothelial and vascular smooth muscle and
cardiac cells' phenotype shifts, resulting in production of inflammatory cytokines. Progressivemolecular disorder
within the heart and arteries over time leads to an excessive allostatic load on the CV system, that results in an
increase and “overshoot” in the inflammatory defense signaling. This age-associatedmolecular disorder-induced
inflammation that accrues in the heart and arteries does not, itself, cause clinical signs or symptoms of CVD. Clinical
signs and symptoms of these CVDs begin to emerge, however, when the age-associated inflammation in the
heart and arteries exceeds a threshold. Thus, an emerging school of thought is that accelerated age-associated alterationswithin
the heart and arteries, per se, ought to be considered to be a type of CVD, because themolecular
disorder and the inflammatory milieu it createswithin the heart and arteries with advancing age are the roots of
the pathophysiology of most cardiovascular diseases, e.g. athersclerosis and hypertension. Because many effects
of aging on the CV system can be delayed or attenuated by changes in lifestyle, e.g. diet and exercise, or by presently
available drugs, e.g. those that suppress Ang II signaling, CV aging is a promising frontier in preventive
cardiology that is not only ripe for, but also in dire need of attention!