Hypertension and cellular senescence

Afsar, Barış; Afşar, Rengin Elsürer

doi:10.1007/s10522-023-10031-4

Cited by 7 publications

(5 citation statements)

References 224 publications

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“…It is interesting to note that endothelial senescence has been implicated in the pathogenesis of systemic hypertension (for a review, see Ref. 63 ) and pulmonary hypertension ( 64 ). Surprisingly, no published data show that systemic hypertension causes endothelial senescence.…”

Section: Discussionmentioning

confidence: 99%

Podocytes from hypertensive and obese mice acquire an inflammatory, senescent, and aged phenotype

McKinzie,

Kaverina,

Schweickart

et al. 2024

American Journal of Physiology-Renal Physiology

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Patients with hypertension or obesity can develop glomerular dysfunction characterized by injury and depletion of podocytes. To better understand the molecular processes involved, young mice were treated with either deoxycorticosterone acetate (DOCA) or fed a high-fat diet (HFD) to induce hypertension or obesity, respectively. The transcriptional changes associated with these phenotypes were measured by unbiased bulk mRNA-sequencing of isolated podocytes from experimental models and their respective controls. Key findings were validated by immunostaining. In addition to a decrease in canonical proteins and reduced podocyte number, podocytes from both hypertensive and obese mice exhibited a sterile inflammatory phenotype characterized by increases in NLRP3 inflammasome, protein cell death-1, and Toll-Like Receptor pathways. Finally, although the mice were young, podocytes in both models exhibited increased expression of senescence and aging genes, including genes consistent with a senescence-associated secretory phenotype. However, there were differences between the hypertension- and obesity-associated senescence phenotypes. Both show stress-induced podocyte senescence characterized by increased p21 and p53. Moreover, in hypertensive mice, this is superimposed upon age-associated podocyte senescence characterized by increased p16 and p19. These results suggest that senescence, aging, and inflammation are critical aspects of the podocyte phenotype in experimental hypertension and obesity in mice.

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Section: Discussionmentioning

confidence: 99%

Podocytes from hypertensive and obese mice acquire an inflammatory, senescent, and aged phenotype

McKinzie,

Kaverina,

Schweickart

et al. 2024

American Journal of Physiology-Renal Physiology

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“…Hypertension has been described as a condition of premature vascular aging, especially endothelial cell senescence, relative to actual chronological age in both hypertensive patients and animal models of hypertension ( McCarthy et al, 2019 ). There are various common pathways that play a role in cellular aging and blood pressure regulation, including but not limited to inflammation, oxidative stress, mitochondrial dysfunction, decreased klotho activity, activation of renin-angiotensin system as well as gut dysbiosis ( Afsar & Afsar, 2023 ). Nonetheless, precise mechanisms by which hypertension accelerates premature aging and causes progressive end-organ damages remain largely elusive.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, we found that an antihypertensive agent, i.e ., propranolol, was able to diminish the upregulation of SASP, thus indicating an association between an increased cellular senescence and hypertension. Since premature aging was indeed observed and implicated in the development and progression of hypertension ( Afsar & Afsar, 2023 ), it is possible that persistent elevation of blood pressure in essential hypertension is linked to the presence of premature vascular aging.…”

Section: Discussionmentioning

confidence: 99%

“…Hypertension is a major health problem worldwide and is highly prevalent in the aging populations ( Mills, Stefanescu & He, 2020 ). However, elevated blood pressure is closely associated not only with increased chronological aging but also with biological aging, ( Afsar & Afsar, 2023 ) Increased blood pressure without proper control imposes structural alterations in several organs leading to organ dysfunction. Chronic hypertension in particular, damages structures and functions of major vascular beds, such as those of the heart, brain and kidneys ( Suvila & Niiranen, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

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Tissue-specific expression of senescence biomarkers in spontaneously hypertensive rats: evidence of premature aging in hypertension

Somsura,

Kamkajon,

Chaimongkolnukul

et al. 2023

PeerJ

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Background Cellular senescence is an age-related physiological process that contributes to tissue dysfunction and accelerated onset of chronic metabolic diseases including hypertension. Indeed, elevation of blood pressure in hypertension coincides with premature vascular aging and dysfunction. In addition, onsets of metabolic disturbance and osteopenia in patients with hypertension have also been reported. It is possible that hypertension enhances premature aging and causes progressive loss of function in multiple organs. However, the landscape of cellular senescence in critical tissues affected by hypertension remains elusive. Materials and Methods Heart, liver, bone, hypothalamus, and kidney were collected from spontaneously hypertensive rats (SHR) and age- and sex-matched normotensive Wistar rats (WT) at 6, 12, 24 and 36 weeks of age (n = 10 animals/group). Changes in mRNA levels of senescence biomarkers namely cyclin-dependent kinase (CDK) inhibitors (CDKIs), i.e., Cdkn2a (encoding p16Ink4a) and Cdkn1a (encoding p21cip1) as well as senescence-associated secretory phenotypes (SASPs), i.e., Timp1, Mmp12, Il6 and Cxcl1, were determined. Additionally, bone collagen alignment and hydroxy apatite crystal dimensions were determined by synchrotron radiation small- and wide-angle X-ray scattering (SAXS/WAXS) techniques. Results Real-time PCR revealed that transcript levels of genes encoding CDKIs and SASPs in the heart and liver were upregulated in SHR from 6 to 36 weeks of age. Expression of Timp1 and Cxcl1 was increased in bone tissues isolated from 36-week-old SHR. In contrast, we found that expression levels of Timp1 and Il6 mRNA were decreased in hypothalamus and kidney of SHR in all age groups. Simultaneous SAXS/WAXS analysis also revealed misalignment of bone collagen fibers in SHR as compared to WT. Conclusion Premature aging was identified in an organ directly affected by high blood pressure (i.e., heart) and those with known functional defects in SHR (i.e., liver and bone). Cellular senescence was not evident in organs with autoregulation of blood pressure (i.e., brain and kidney). Our study suggested that cellular senescence is induced by persistently elevated blood pressure and in part, leading to organ dysfunction. Therefore, interventions that can both lower blood pressure and prevent cellular senescence should provide therapeutic benefits for treatment of cardiovascular and metabolic consequences.

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“…As elegantly reviewed and displayed [50], senescent cardiovascular cells exert both beneficial and detrimental effects on cardiovascular diseases context‐dependently. Although senescence is associated with atherosclerosis, heart rupture post‐acute myocardial infarction, cardiac aging, abdominal aortic aneurysm, and hypertension [51, 52], there is strong evidence that CS also participates in heart regeneration and cardiac remodeling [53].…”

Section: Cellular Senescence and Major Clinical Implicationsmentioning

confidence: 99%

Focus on senescence: Clinical significance and practical applications

Boccardi,

Orr,

Polidori

et al. 2024

J Intern Med

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The older population is increasing worldwide, and life expectancy is continuously rising, predominantly thanks to medical and technological progress. Healthspan refers to the number of years an individual can live in good health. From a gerontological viewpoint, the mission is to extend the life spent in good health, promoting well‐being and minimizing the impact of aging‐related diseases to slow the aging process. Biologically, aging is a malleable process characterized by an intra‐ and inter‐individual heterogeneous and dynamic balance between accumulating damage and repair mechanisms. Cellular senescence is a key component of this process, with senescent cells accumulating in different tissues and organs, leading to aging and age‐related disease susceptibility over time. Removing senescent cells from the body or slowing down the burden rate has been proposed as an efficient way to reduce age‐dependent deterioration. In animal models, senotherapeutic molecules can extend life expectancy and lifespan by either senolytic or senomorphic activity. Much research shows that dietary and physical activity‐driven lifestyle interventions protect against senescence. This narrative review aims to summarize the current knowledge on targeting senescent cells to reduce the risk of age‐related disease in animal models and their translational potential for humans. We focused on studies that have examined the potential role of senotherapeutics in slowing the aging process and modifying age‐related disease burdens. The review concludes with a general discussion of the mechanisms underlying this unique trajectory and its implications for future research.

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Hypertension and cellular senescence

Cited by 7 publications

References 224 publications

Podocytes from hypertensive and obese mice acquire an inflammatory, senescent, and aged phenotype

Podocytes from hypertensive and obese mice acquire an inflammatory, senescent, and aged phenotype

Tissue-specific expression of senescence biomarkers in spontaneously hypertensive rats: evidence of premature aging in hypertension

Focus on senescence: Clinical significance and practical applications

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