Using senolytics to treat fibrosis shows promise

Latest articles

Top 10 heath gadgets to live longer and healthier

Top ten health gadgets for the longevity enthusiasts in your life. As the holiday season kicks off with Thanksgiving this year, Christmas is right around...

Eliminating senescent cells in fat can alleviate signs of diabetes

Deleting dysfunctional cells could lead to game-changing treatments for diabetes and other metabolic diseases. Eliminating old, dysfunctional cells in human fat also alleviates signs of...

Longevica: bridging the gap between longevity science and consumers

Longevica CEO sheds further light on work to develop an “open research platform” to drive both longevity science and commercialisation. Following yesterday’s $2.5 million funding...

Longevity Science Summit: care of aging population talks continue

Our dive into Longevity Week's Science Summit continues... Last week, Longevity.Technology was lucky enough to attend Longevity Forum's Science Summit at Oxford's Oriel College, part...

Most read

New supplement slows aging and promotes weight loss

Sugar-proof your way to a longer life. Reducing AGEs to slow aging and increase weight loss – how one supplement is fighting the war...

An antiaging supplement that also reduces appetite?

One for the AGEs: Juvify signs IP licensing deal with Buck Institute for GLYLO antiaging supplement that aims to reduce glycation. A researcher at the...

Resveratrol – the small molecule with big antiaging ideas

When it comes to antiaging molecules, we can learn a thing or two from plants. As so often in natural world, plants have a few...

Editor's picks

Top 10 heath gadgets to live longer and healthier

Top ten health gadgets for the longevity enthusiasts in your life. As the holiday season kicks off with Thanksgiving this year, Christmas is right around...

Eliminating senescent cells in fat can alleviate signs of diabetes

Deleting dysfunctional cells could lead to game-changing treatments for diabetes and other metabolic diseases. Eliminating old, dysfunctional cells in human fat also alleviates signs of...

Longevica: bridging the gap between longevity science and consumers

Longevica CEO sheds further light on work to develop an “open research platform” to drive both longevity science and commercialisation. Following yesterday’s $2.5 million funding...

Click the globe for translations.

Increasing evidence shows a direct link between fibrosis in the extracellular matrix and cellular senescence.

Mounting evidence suggests a direct link between cellular senescence and tissue damage due to the deposition of extracellular matrix (ECM) components, a condition also known as fibrosis. Notably, elimination of senescent cells alleviates fibrosis in animal models [1]. However, the relevance of this interplay between senescent cells and ECM components in aging and age-related diseases remains poorly understood.

Longevity.Technology: In a review article recently published in the journal Clinical Science, Blokland et al. indicate that ECM stiffening, a major characteristic of fibrosis and an emerging hallmark of aging [2], may cause cellular senescence. They also point out that the direct regulation of cellular senescence by ECM may represent a key mechanistic link between fibrosis, cellular senescence, and aging [3].  

Deposition of collagen and other ECM components is the leading cause of organ dysfunction associated with fibrosis. Although the cause of ECM deposition remains unknown, studies suggest that cellular senescence may play a key role in fibrosis.

Increased ECM stiffness due to alterations in ECM composition and increased cross-linking of the ECM components is the main feature of fibrosis. In fact, the mechanical characteristics of ECM and ECM stiffening play a more important role in fibrotic diseases than ECM deposition. Increased cross-linking of ECM fibres has been associated with resistance to proteolytic degradation by matrix metallopeptidases. These alterations in proteolytic degradation significantly impact cellular functions, particularly in fibroblasts. The increased activation and proliferation of fibroblast due to ECM stiffening links ECM alterations to tissue damage in fibrotic disease [3, 4].

 


 

 

“The cell cycle arrest is needed to reduce the amount of collagen that the cells synthesize. Matrix metalloproteinases included in SASP destroy excessive collagen, while pro-inflammatory cytokines attract immune cells to finalize the cleanup.”

 

 


 

Additionally, ECM stiffening promotes the activation of transforming growth factor-β (TGF-β), which is known to induce cellular senescence in numerous cell types, favouring the onset of age-related diseases. Interestingly, senolytic agents (e.g., quercetin and dasatinib) have been shown to alleviate fibrosis in animal models, in addition to eliminating senescent cells [1]. The ability of senolytics to reduce fibrosis is believed to be mediated through the modulation of senescence-associated secretory phenotype (SASP) and inflammaging [3].

“The cell cycle arrest is needed to reduce the amount of collagen that the cells synthesize. Matrix metalloproteinases included in SASP destroy excessive collagen, while pro-inflammatory cytokines attract immune cells to finalize the cleanup. The anti-fibrotic nature of cellular senescence has been demonstrated in multiple studies,” said Alexander Fedintsev, a scientist at the Moscow Institute of Physics and Technology working on the identification of aging biomarkers [5]. “My bet is that cells can sense the excess of collagen via ECM stiffening, and if the stiffness exceeds a certain threshold, this might launch the cellular senescence sequence. But the increase in stiffness is exactly what happens during normal aging due to non-enzymatic cross-link formation!”

The results of the first human pilot study of senolytics have recently been published in the journal EBioMedicine (ClinicalTrials.gov: NCT02874989) [6]. The study has shown that quercetin and dasatinib significantly improved the physical condition of patients with idiopathic pulmonary fibrosis. Furthermore, the senolytic treatment reduced the levels of IL-6, MMP, and TIMP2, which are implicated in ECM remodelling and fibrosis.

Notwithstanding promising preliminary data showing that targeting senescence may be a promising therapeutic approach for patients with fibrotic diseases, randomized large-cohort controlled trials are warranted to confirm the clinical usefulness of senolytics for patients with fibrosis and other senescence-related diseases.

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4412760/

[2] https://pubmed.ncbi.nlm.nih.gov/32540391/

[3] https://bit.ly/3lCgxbU

[4] https://bit.ly/3lB7MPy

[5] https://www.lifespan.io/news/a-new-hallmark-of-aging-proposed/

[6] https://pubmed.ncbi.nlm.nih.gov/30616998/

 

Image by Gerd Altmann from Pixabay

Christos Evangelou
Since the completion of his undergraduate and doctoral studies in Molecular Biosciences, Christos has been working in the medical communications industry, driven by his passion for communicating sciences. Apart from helping researchers to publish their studies, Christos writes articles related to sciences and medicine.

Most popular

New supplement slows aging and promotes weight loss

Sugar-proof your way to a longer life. Reducing AGEs to slow aging and increase weight loss – how one supplement is fighting the war...

An antiaging supplement that also reduces appetite?

One for the AGEs: Juvify signs IP licensing deal with Buck Institute for GLYLO antiaging supplement that aims to reduce glycation. A researcher at the...

Resveratrol – the small molecule with big antiaging ideas

When it comes to antiaging molecules, we can learn a thing or two from plants. As so often in natural world, plants have a few...

Tree of Longevity – understanding how supplements work

Pathways? Hallmarks? Biomarkers? Understanding the longevity supplements lingo can help you make better choices for your healthspan. Longevity supplements differ from other 'generic supplements' as...

Related articles

Eliminating senescent cells in fat can alleviate signs of diabetes

Deleting dysfunctional cells could lead to game-changing treatments for diabetes and other metabolic diseases. Eliminating old, dysfunctional cells in human fat also alleviates signs of...

Longevica: bridging the gap between longevity science and consumers

Longevica CEO sheds further light on work to develop an “open research platform” to drive both longevity science and commercialisation. Following yesterday’s $2.5 million funding...

Young blood: discover the possibilities of plasma based therapy

The evolution of plasma-based therapeutics is accelerating – our FREE report cuts through the young blood hype for the lowdown on the latest therapies. Our...

Longevica raises $2.5 million for open research platform

$2.5m in funding to support longevity research platform and study to accelerate the discovery of life extension mechanisms, launching in 2022. Longevica, a life science...

Fountain’s $15m to “restore youthful resilience to cells”

Longevity funding: Eli Lilly and R42 Group join the party as Khosla-backed biopharma brings total Series A financing to $26 million. Longevity biopharma Fountain Therapeutics...

    Subscribe to our newsletter