secretory phenotype
Recently Published Documents


TOTAL DOCUMENTS

451
(FIVE YEARS 242)

H-INDEX

46
(FIVE YEARS 13)

2021 ◽  
Vol 4 (2) ◽  
pp. 33
Author(s):  
Filda Vionita Irene De Lime ◽  
Novi Silvia Hardiany

Cellular senescence is one of the defense mechanisms of cells against oncogenic signals by permanently stopping the proliferation of the cell. Senescence cells show a similar characteristic, one of them is senescence-associated secretory phenotype (SASP). SASPs secrete various components, divided according to the type of molecule secreted and based on their mechanism of action against target cells. The main components of SASP are pro-inflammatory mediators. SASP performs dual and contradictory roles, which concurrently provides beneficial effects such as tumor suppression due to the termination of proliferation, recruitment of immune cells, and tissue repair. On the other hand, SASP produces detrimental effects on cells undergoing the senescence process as well as cells in the surrounding environment by increasing tumorigenesis. This review article explains the various components of the SASP, the role of SASP in the inflammatory process, tumor suppression, and tumorigenesis.


2021 ◽  
Vol 9 (1) ◽  
pp. 1
Author(s):  
Adwiteeya Misra ◽  
Cameron D. Baker ◽  
Elizabeth M. Pritchett ◽  
Kimberly N. Burgos Villar ◽  
John M. Ashton ◽  
...  

The neonatal mammalian heart exhibits a remarkable regenerative potential, which includes fibrotic scar resolution and the generation of new cardiomyocytes. To investigate the mechanisms facilitating heart repair after apical resection in neonatal mice, we conducted bulk and spatial transcriptomic analyses at regenerative and non-regenerative timepoints. Importantly, spatial transcriptomics provided near single-cell resolution, revealing distinct domains of atrial and ventricular myocardium that exhibit dynamic phenotypic alterations during postnatal heart maturation. Spatial transcriptomics also defined the cardiac scar, which transitions from a proliferative to secretory phenotype as the heart loses regenerative potential. The resolving scar is characterized by spatially and temporally restricted programs of inflammation, epicardium expansion and extracellular matrix production, metabolic reprogramming, lipogenic scar extrusion, and cardiomyocyte restoration. Finally, this study revealed the emergence of a regenerative border zone defined by immature cardiomyocyte markers and the robust expression of Sprr1a. Taken together, our study defines the spatially and temporally restricted gene programs that underlie neonatal heart regeneration and provides insight into cardio-restorative mechanisms supporting scar resolution.


2021 ◽  
Vol 22 (23) ◽  
pp. 13173
Author(s):  
Lauréline Roger ◽  
Fanny Tomas ◽  
Véronique Gire

Cellular senescence entails a state of an essentially irreversible proliferative arrest in which cells remain metabolically active and secrete a range of pro-inflammatory and proteolytic factors as part of the senescence-associated secretory phenotype. There are different types of senescent cells, and senescence can be induced in response to many DNA damage signals. Senescent cells accumulate in different tissues and organs where they have distinct physiological and pathological functions. Despite this diversity, all senescent cells must be able to survive in a nondividing state while protecting themselves from positive feedback loops linked to the constant activation of the DNA damage response. This capacity requires changes in core cellular programs. Understanding how different cell types can undergo extensive changes in their transcriptional programs, metabolism, heterochromatin patterns, and cellular structures to induce a common cellular state is crucial to preventing cancer development/progression and to improving health during aging. In this review, we discuss how senescent cells continuously evolve after their initial proliferative arrest and highlight the unifying features that define the senescent state.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 300-300
Author(s):  
Marco Demaria

Abstract Aging is at the root of age-related diseases and therapies targeting basic age-associated mechanisms have the potential to extend healthy lifespan. A common feature of older organisms is the accumulation of senescent cells – cells that have irreversibly lost the capacity to undergo replication. Senescent cells are characterized by an irreversible cell cycle arrest and by the Senescence-Associated Secretory Phenotype (SASP), which include many tissue remodeling and pro-inflammatory factors. Senescent cells are intermittently present during embryogenesis and in young organisms. On the contrary senescent cells accumulate and persist in aging tissues. Significantly, these persistent senescent cells can drive low-grade chronic inflammation, and their genetic or pharmacological elimination is sufficient to delay a number of diseases and to improve health span. Here, I will discuss the mechanisms by which senescent cells can promote tissue aging and dysfunction and the potential of targeting senescent cells to delay human aging.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Rui Liu ◽  
Juanjuan Cui ◽  
Yating Sun ◽  
Wentao Xu ◽  
Ziming Wang ◽  
...  

AbstractAging disrupts the maintenance of liver homeostasis, which impairs hepatocyte regeneration and aggravates acute liver injury (ALI), ultimately leading to the development of acute liver failure (ALF), a systemic inflammatory response, and even death. Macrophages influence the progression and outcome of ALI through the innate immune system. However, it is still unclear how macrophages regulate ALI during aging. The variation in macrophage autophagy with aging and the influence on macrophage polarization and cytokine release were assessed in BMDMs in vitro. Then, after BMDMs subjected to several treatments were intravenously or intraperitoneally injected into mice, thioacetamide (TAA)-induced ALI (TAA-ALI) was established, and its effects on inflammation, injury, and mortality were assessed. We found that aging aggravated the liver injury, along with increases in the levels of proinflammatory mediators, presenting a senescence-associated secretory phenotype (SASP), which promoted macrophage polarization to the M1 phenotype. In addition, autophagy levels decreased significantly in aged mice, which was ascribed to ATG5 repression during aging. Notably, enhancing autophagy levels in aged BMDMs restored macrophage polarization to that observed under young conditions. Finally, autophagy restoration in aged BMDMs enhanced the protective effect against TAA-ALI, similar to M2 macrophages induced by IL-4. Overall, we demonstrated that the influence of aging on macrophage polarization is an important aggravating factor in TAA-ALI, and the autophagy in macrophages is associated with the aging phenotype.


2021 ◽  
Vol 16 (1) ◽  
pp. 57-65
Author(s):  
Chen-Chen Mao ◽  
Xiaoxiao Cai

As the proportion of the elderly population increases, more and more people suffer from aging-related diseases. Even if aging is inevitable, prolonging the time of healthy aging, delaying the progression of aging-related diseases, and the incidence of morbidity can greatly alleviate the pressure on individuals and society. Current research and exploration in the field of materials related to aging are expanding tremendously. Here, we present a summary of recent research in the field of nanomaterials relevant to aging. Some nanomaterials, such as silica nanomaterials (NMs) and carbon nanotubes, cause damage to the cells similar to aging processes. Other nanomaterials such as fullerenes and metalbased nanomaterials can protect the body from endogenous and exogenous harmful substances such as ROS by virtue of their excellent reducing properties. Another new type of nucleic acid nanomaterial, tetrahedral framework nucleic acids, works effectively against cell damage. This material selectively clears existing senescent cells in the tissue and thus prevents the development of the chronic inflammatory environment caused by senescent cells secreting senescence-associated secretory phenotype to the surroundings. We believe that nanomaterials have tremendous potential to advance the understanding and treatment of aging-related disorders, and today's research only represents the beginning stages.


2021 ◽  
Vol 42 ◽  
pp. 401-414
Author(s):  
C Voskamp ◽  
◽  
LA Anderson ◽  
WJLM Koevoet ◽  
S Barnhoorn ◽  
...  

Mesenchymal stem cells (MSCs) are promising cells for regenerative medicine therapies because they can differentiate towards multiple cell lineages. However, the occurrence of cellular senescence and the acquiring of the senescence-associated secretory phenotype (SASP) limit their clinical use. Since the transcription factor TWIST1 influences expansion of MSCs, its role in regulating cellular senescence was investigated. The present study demonstrated that silencing of TWIST1 in MSCs increased the occurrence of senescence, characterised by a SASP profile different from irradiation-induced senescent MSCs. Knowing that senescence alters cellular metabolism, cellular bioenergetics was monitored by using the Seahorse XF apparatus. Both TWIST1-silencing-induced and irradiation-induced senescent MSCs had a higher oxygen consumption rate compared to control MSCs, while TWIST1-silencing-induced senescent MSCs had a low extracellular acidification rate compared to irradiation-induced senescent MSCs. Overall, data indicated how TWIST1 regulation influenced senescence in MSCs and that TWIST1 silencing-induced senescence was characterised by a specific SASP profile and metabolic state.


Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3315
Author(s):  
Sven E. Niklander ◽  
Daniel W. Lambert ◽  
Keith D. Hunter

Over recent decades, the field of cellular senescence has attracted considerable attention due to its association with aging, the development of age-related diseases and cancer. Senescent cells are unable to proliferate, as the pathways responsible for initiating the cell cycle are irreversibly inhibited. Nevertheless, senescent cells accumulate in tissues and develop a pro-inflammatory secretome, known as the senescence-associated secretory phenotype (SASP), which can have serious deleterious effects if not properly regulated. There is increasing evidence suggesting senescent cells contribute to different stages of carcinogenesis in different anatomical sites, mainly due to the paracrine effects of the SASP. Thus, a new therapeutic field, known as senotherapeutics, has developed. In this review, we aim to discuss the molecular mechanisms underlying the senescence response and its relationship with cancer development, focusing on the link between senescence-related inflammation and cancer. We will also discuss different approaches to target senescent cells that might be of use for cancer treatment.


Sign in / Sign up

Export Citation Format

Share Document