Pathways for salvage and protection of the heart under stress: novel routes for cardiac rejuvenation

Abstract

The world population is aging, and by 2017, there will be more people over the age of 65 than under age 5, and by 2050, two billion of the estimated nine billion people on Earth will be older than 60. Aging itself is a major cardiovascular risk factor, affecting morbidity and mortality of the aging population. At the same time, aging increases the likelihood of the presence of other risk factors. The aged myocardium is characterized by several structural and functional progressive changes that impair its ability to respond appropriately to stressful conditions. Although some progress to understand the complex mechanisms that underlie these phenotypic changes, the molecular pathways that determine the balance between aging and rejuvenation in the aged myocardium still remain elusive. In this article, we review molecular mechanisms responsible for the phenotypic changes observed with aging in the heart, providing insight into molecular pathways and pharmacological interventions that may rejuvenate the aged myocardium. A better understanding of these pathways is essential for determining their therapeutic potential in humans, improving the possibility that the increase in life expectancy that we are observing will be accompanied by a parallel increase in healthspan.

Oxidative Stress, Inflammation, and Vascular Aging in Hypertension

“…4 This is, in part, dependent on cellular senescence and growth arrest. 5 Although hypertension and atherosclerosis are associated with accumulation of cellular senescence markers in the vascular wall, these conditions are often associated with vascular dysfunction rather than simple loss of proliferative capacity. 6 For example, risk factors for cardiovascular disease, such as hypertension, smoking, hyperlipidaemia, or diabetes mellitus are associated with accelerated decline of vascular function.…”

Biochemical algorithms of early diagnostic of metabolic remodeling and cardiac hypertrophy in patients with diabetic mellitus and chronic heart failure cause by ischemic heart disease

“…Высокий уровень глюкозы и жиров при СД 2, преобладание окисления жирных кислот (ЖК) негативно влияют на степень окисления глюкозы при СД 2. Диабетическое сердце почти полностью переключается на окисление ЖК в митохондриях (Мх) для продукции аденозинтрифосфата при резком снижении инсулинзависимого поглощения глюкозы -состояние, получившее название «метаболическая жесткость», интимные патогенетические механизмы развития которой остаются неизвестными [1][2][3]. Было показано, что гипергликемия per se может быть триггером клеточного поражения независимо от утилизации ЖК, например в эндотелиальных клетках [4].…”

Role of circulating factors in cardiac aging

“…The aging process is responsible itself for several structural and functional changes and for the increased incidence of several cardiovascular risk factors such as hypertension, dyslipidemia and diabetes (2,3). The concepts that circulating factors may regulate the aging process have shed the light on this issue contributing to the development of novel therapeutic strategies to promote healthy aging (4)(5)(6).…”