Cellular senescence is an evolutionarily conserved process that is physiologically involved in the renewal of the tissues through elimination of cells with an exhausted function. Classically correlated to progressive shortening of the telomeres as a part of the mechanism counting the number of cellular generations and preventing genomic instability (the so-called Hayflick limit), cellular senescence has also been associated to various signaling, ultimately contributing to tissue damage and premature aging of the cardiovascular system.
On a cell biology point of view, senescence is described as an irreversible status of proliferative arrest, leading cells to exit definitively from the cell cycle before tissue removal by immune cells or cell death by apoptosis. Recent findings, however, show the occurrence of various cellular stresses due to risk conditions (e.g. diabetes, hypertension, dyslipidemia) may lead to excessive accumulation of senescent cells. This is associated with premature aging due to permanent inflammation favored by the so-called senescence-associated-secretory-phenotype (SASP). This phenomenon seems particularly evident in various cardiovascular pathologies such as degeneration of cardiac valves, cardiomyopathies, cardiac fibrosis and atherosclerosis.
Recent pieces of experimental evidence have shown that specific compounds, called senolytics, can efficiently target cells exhibiting markers of irreversible senescence (i.e. p16INK protein expression). This has raised the hope that tissues with a high impact of cellular senescence may be pharmacologically ‘rejuvenated’ by eliminating senescent cells and promoting their replacement by biologically younger cells. On the other hand, since the control of senescent status is operated by a variety of molecular mechanisms involving metabolism, epigenetics, coding/non-coding RNAs, inflammation and even mechanical cues, new research is necessary to derive a balanced view of the multilevel interaction of these factors and come up with new therapies.
The present Research Topic has the specific aim to collect original research articles and reviews describing the pathophysiology of cardiovascular aging with respect to the extent of cellular senescence.
In particular, issues that we expect to cover include, but are not strictly limited to:
1) Molecular mechanisms crucially involved in cardiovascular cell senescence, including miRNAs, long non-coding RNAs, circular RNAs, and transposable elements.
2) Involvement of metabolism in cardiovascular cell senescence, including senescence-specific cell metabolism.
3) Loss of proteostasis control in cardiovascular cell senescence.
4) Modulation of cell senescence by physical forces, including biophysical control of cell senescence, nuclear mechanics and cell senescence.
5) Epigenetic control of cell senescence, including chromatin remodeling in cell senescence.
6) Pathogenetic role of immunosenescence in cardiovascular aging and pathology.
7) Senotherapeutics, including senomorphic drugs, senolytic drugs and immune-mediated clearance of senescent cells.
Cellular senescence is an evolutionarily conserved process that is physiologically involved in the renewal of the tissues through elimination of cells with an exhausted function. Classically correlated to progressive shortening of the telomeres as a part of the mechanism counting the number of cellular generations and preventing genomic instability (the so-called Hayflick limit), cellular senescence has also been associated to various signaling, ultimately contributing to tissue damage and premature aging of the cardiovascular system.
On a cell biology point of view, senescence is described as an irreversible status of proliferative arrest, leading cells to exit definitively from the cell cycle before tissue removal by immune cells or cell death by apoptosis. Recent findings, however, show the occurrence of various cellular stresses due to risk conditions (e.g. diabetes, hypertension, dyslipidemia) may lead to excessive accumulation of senescent cells. This is associated with premature aging due to permanent inflammation favored by the so-called senescence-associated-secretory-phenotype (SASP). This phenomenon seems particularly evident in various cardiovascular pathologies such as degeneration of cardiac valves, cardiomyopathies, cardiac fibrosis and atherosclerosis.
Recent pieces of experimental evidence have shown that specific compounds, called senolytics, can efficiently target cells exhibiting markers of irreversible senescence (i.e. p16INK protein expression). This has raised the hope that tissues with a high impact of cellular senescence may be pharmacologically ‘rejuvenated’ by eliminating senescent cells and promoting their replacement by biologically younger cells. On the other hand, since the control of senescent status is operated by a variety of molecular mechanisms involving metabolism, epigenetics, coding/non-coding RNAs, inflammation and even mechanical cues, new research is necessary to derive a balanced view of the multilevel interaction of these factors and come up with new therapies.
The present Research Topic has the specific aim to collect original research articles and reviews describing the pathophysiology of cardiovascular aging with respect to the extent of cellular senescence.
In particular, issues that we expect to cover include, but are not strictly limited to:
1) Molecular mechanisms crucially involved in cardiovascular cell senescence, including miRNAs, long non-coding RNAs, circular RNAs, and transposable elements.
2) Involvement of metabolism in cardiovascular cell senescence, including senescence-specific cell metabolism.
3) Loss of proteostasis control in cardiovascular cell senescence.
4) Modulation of cell senescence by physical forces, including biophysical control of cell senescence, nuclear mechanics and cell senescence.
5) Epigenetic control of cell senescence, including chromatin remodeling in cell senescence.
6) Pathogenetic role of immunosenescence in cardiovascular aging and pathology.
7) Senotherapeutics, including senomorphic drugs, senolytic drugs and immune-mediated clearance of senescent cells.