senolytics, 세포 노화의 처리

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피부세포의 노화는 60-80세에 급격히 진행함

간세포의 노화는?

근육세포의 노화는?

글루텐 문제로 어떤 사람은 치매, 어떤 사람은 정신병, 어떤 사람은 아토피?

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Ursolic acid induces mitochondrial biogenesis through the activation of AMPK and PGC-1 in C2C12 myotubes: a possible mechanism underlying its beneficial effect on exercise endurance.

Melatonin: A Mitochondrial Targeting Molecule Involving Mitochondrial Protection and Dynamics

Melatonin in Mitochondria: Mitigating Clear and Present Dangers

Russel J. Reiter

05 FEB 2020https://doi.org/10.1152/physiol.00034.2019

• Review Article - nature
• Open Access
• Published: 02 June 2021

Melatonin’s neuroprotective role in mitochondria and its potential as a biomarker in aging, cognition and psychiatric disorders

• Review Article - Nature medicine 영향력지수 45점
• Published: 11 August 2022

Cellular senescence and senolytics: the path to the clinic

https://www.nature.com/articles/s41591-022-01923-y

Trends Biochem Sci. Author manuscript; available in PMC 2020 Nov 9.   - 영향력지수 9.5

Published in final edited form as:

Trends Biochem Sci. 2020 Jul; 45(7): 578–592.

Senescent Cells: Emerging Targets for Human Aging and Age-Related Diseases

Distinct alterations in molecular pathways of cellular senescence result in morphological changes. Senescent cells are enlarged, flattened, and have an irregular cell shape (not shown). Their nuclear integrity is compromised due to the loss of lamin B1 and exclusion of the high mobility group protein B1 (HMGB1), accompanied by the emergence of cytoplasmic chromatin fragments (CCFs). Senescent cells have increased lysosomal content, as manifested by elevated β-galactosidase (SA-β-gal) activity, with an increased number of large but dysfunctional mitochondria that produce high levels of reactive oxygen species (ROS). There is usually an enhanced level of lipofuscin in the cytoplasm and upregulation of p16 INK4a /p21 CIP1  in the nucleus. Biosynthesis and extracellular secretion of a large number of proinflammatory and proapoptotic factors [senescence-associated secretory phenotype (SASP)] is robust and constitutes one of the major features of senescent cells. Yellow arrows: signal transduction or molecular traffic; purple arrows: DNA fragment transportation; white arrows: up- or downregulation of expression‎ or activities. Red text: representative typical hallmarks of senescent cells. Different colors of the outlines of SASP factors indicate various types of secreted molecules (e.g., cytokines, chemokines, and growth factors). Abbreviations: DDR, DNA damage response; MMP, matrix metalloproteinase; PTM, post-translational modification.

Aging is the leading risk factor for many chronic diseases, including but not limited to cancers, metabolic syndrome, and musculoskeletal, cardiovascular, and neurodegenerative disorders. Recent studies suggest that targeting fundamental aging mechanisms may be a better solution than targeting each chronic pathology individually in order to increase healthspan and delay multimorbidity. Pilot efforts have recently been made to therapeutically target cellular senescence, including selectively eliminating senescent cells by inducing their passive apoptosis (senolytic treatment) (A), and modulating the senescence-associated secretory phenotype (SASP) (SASP suppression, or senostatics) by blocking the SASP development or interfering with the function of its key components in the tissue microenvironment (B). In each figure, yellow arrows represent stimulating or promotive actions, while red arrows are suppressive or counteractive. Agents within yellow or orange boxes are exemplifying senolytics (A) and SASP inhibitors (B), respectively. Abbreviations: AMPK, AMP-activated protein kinase; OXR1, oxidation resistance 1; ROS, reactive oxygen species.

Cellular senescence takes longer to become established than other cell fates, such as replication, differentiation, apoptosis or necrosis. From initiation to the attainment of a completed state of cellular senescence takes from 10 days to 6 weeks, at least in cell culture, depending on the cell type and the inducers driving the cell into the senescent fate.

Senescent cells and macrophages: key players for regeneration? - 영향력지수 9점

https://royalsocietypublishing.org/doi/pdf/10.1098/rsob.200309

Figure 1. The hallmarks, causes and effects of cellular senescence. (a) The key features of a senescent cell, which include an enlarged and irregular/flattened shape [6], DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS) [9] and foci [10], altered gene expression‎ [8] and cell cycle arrest [7], mitochondrial dysfunction and release of reactive oxygen species (ROS) [12,13], protein modifications [14], lipofuscin granules, expression‎ of SA-β-galactosidase [16] and release of SASP factors [14,17]. (b) Cellular senescence can occur in response to cellular or DNA damage [18], oncogene, mitogen and cytokine signalling [19], telomere attrition/shortening [20], ionizing radiation [21] and anti-cancer drugs [22]. (c) Cellular senescence plays a dual role during development [23,24] and throughout tissue repair and regeneration [25,26], where it can promote the clearance of cell debris, reduces fibrosis, elicits epigenetic alterations and acts as a potent barrier against tumorigenesis, while also leading to senescence spread, DNA damage, further tissue injury, and ultimately leading to age-associated tissue deterioration and pathologies. Created with Biorender.com.

Programmed Cell Senescence during Mammalian Embryonic Development

https://www.cell.com/fulltext/S0092-8674(13)01295-6 

Cellular Senescence and Senotherapies in the Kidney: Current Evidence and Future Directions

https://www.frontiersin.org/articles/10.3389/fphar.2020.00755/full

Mechanisms and Regulation of Cellular Senescence.pdf

987.11KB

Lipids as Regulators of Cellular Senescence

- 세포 노화... 조절자로서 Lipid

https://www.frontiersin.org/articles/10.3389/fphys.2022.796850/full

FIGURE 1.  Features of senescent cells. Senescent cells are in a state of permanent cell cycle arrest and display several key features including lysosomal changes (SA-β-gal and lipofuscin), p53, p21, and/or p16 expression‎ and a SASP program consisting of multiple cytokines, chemokines, and ECM remodeling enzymes. Senescent cells reprogram their metabolism as well heavily altering lipid metabolism.