Senolytics research shows Longevity progress

Latest articles

The Alliance for Longevity Initiatives – fighting aging

Advancing legislation and policies that aim to increase healthy human lifespan. Longevity is a journey that would be good to imagine we're all taking together;...

Team builds first living robots – that can reproduce

AI-designed Xenobots reveal entirely new form of biological self-replication which could prove promising for regenerative medicine. Birds do it, bees do it... now even living...

Aging in place trailblazer focus – Carewell

Carewell – aiding individuals through their caregiving journey with empathy and knowledge. Over the coming weeks, we will be bringing you extracts from 7 trailblazer...

Humanpeople raising £700k for AI preventative health platform

Digital preventative health platform combines blood, DNA and microbiome testing to power up your healthspan with highly personalised supplements. DISCLOSURE: Longevity.Technology (a brand of...

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

The Alliance for Longevity Initiatives – fighting aging

Advancing legislation and policies that aim to increase healthy human lifespan. Longevity is a journey that would be good to imagine we're all taking together;...

Team builds first living robots – that can reproduce

AI-designed Xenobots reveal entirely new form of biological self-replication which could prove promising for regenerative medicine. Birds do it, bees do it... now even living...

Aging in place trailblazer focus – Carewell

Carewell – aiding individuals through their caregiving journey with empathy and knowledge. Over the coming weeks, we will be bringing you extracts from 7 trailblazer...

Click the globe for translations.

Senolytic research in humans may be in its infancy, but there is reason for cautious optimism.

Last week we reported on biotech company UNITY’s decision to shelve its lead programme following poor results. UNITY stated that it “does not anticipate progressing UBX0101 [a small molecule senolytic] into pivotal studies.”

There have also been concerns raised about using the cancer drug dasatinib with quercetin (DQ), a polyphenol common in plants, as a senolytic therapy; the Forever Healthy Foundation issued a risk-benefit analysis that advised against this therapy “until there are more published results showing benefits in humans.”

Longevity.Technology: DQ, or not DQ, that is the question. This therapy is still in its infancy, as far as research goes, but just because it’s not on the shelves doesn’t mean we shouldn’t be optimistic about results from early trials. Of course, many treatments don’t make it out of clinical trials, but a Mayo Clinic paper shows positive results and we eagerly anticipate the full findings in due course.

Senolytics target senescent cells – cells that have reached their division limit, but forgotten to die; instead they hang around, emitting potentially-harmful chemicals that encourage nearby healthy cells to also become senescent. Senescent cells reduce tissue repair, increase chronic inflammation, contribute to frailty syndrome, sarcopenia, neurodegeneration and raise the risk of cancer and other age-related diseases.

LaTonya Hickson, MD, and her Mayo Clinic colleagues showed in a Phase 1 pilot study that a 3-day oral course of dasatinib plus quercetin decreased senescent cell abundance when administered to nine people with an age range of 55-79 years [1].

The DQ senolytic did this by “selectively eliminating senescent cells by transiently disabling pro-survival networks that defend them against their own apoptotic environment … to date, no peer-reviewed study has directly demonstrated that senolytics decrease senescent cells in humans [2].”


 

“The findings reported here are preliminary results from an ongoing clinical trial of senolytics for treating dysfunction in patients with diabetic chronic kidney disease. Fewer than 150 subjects have been treated with these drugs in the context of clinical trials that we are aware of so far … “

 


 

https://marlin-prod.literatumonline.com/cms/attachment/aa8f334a-c3d7-4bed-8a69-8c29b09a88d3/gr1.jpg
Fig. 1D + Q decreases human adipose tissue senescent cells. (a). D + Q significantly reduced (p = 0·001) abdominal subcutaneous adipose tissue p16INK4A+ cells. Raw values were reduced by 35% in sections of adipose tissue biopsied at Day 14 (11 days after the last dose of a 3-day course of the senolytics) vs. at baseline (Day 0). At Day 0, there were 3·18 ± 0·64 p16INK4A+ cells/100 adipocytes (means ± SEM in 30 fields [400 × 300 μm] at 40× magnification). Means, standard errors, and standard deviations are shown in these “box and whisker” plots. The y axis shows p16INK4A+ cells in the 2 biopsies from each subject at Days 0 and 14 as % of each other (Arbitrary Units). N = 9 subjects; Welch’s unpaired 2-tailed t-test for unequal variances. Representative images at Days 0 and 14 are shown. (b). D + Q significantly reduced (p = 0·009) adipose tissue p21CIP1+ cells. Raw values were decreased 17% by 11 days after completing D + Q treatment. At baseline (Day 0), there were 3·82 ± 0·65 p21CIP1+ cells/100 adipocytes (N = 9 subjects; means ± SEM). Representative images are shown. (c). D + Q significantly reduced (p = 0·005) adipose tissue SA-βgal-expressing cells. Raw values were decreased by 62% by 11 days after completing D + Q treatment. At baseline (Day 0), there were 8·76 ± 2·51 SAβgal+ cells/100 nuclei (N = 9 subjects; mean ± SEM). Representative images are shown. Scale bars = 100 μm. Exact p values are indicated. Colours indicate each individual’s values on Days 0 and 14. Source: The Lancet
The research team found that DQ “alleviated physical dysfunction in patients with idiopathic pulmonary fibrosis (IPF), a progressive, fatal, cellular senescence-associated disease. In another clinical trial, prolonged D administration to patients with systemic sclerosis appeared to reduce the SASP and other senescence markers in skin biopsies.

“Key markers of senescent cell burden were decreased in adipose tissue and skin biopsied from subjects 11 days after completing the 3-day course of D + Q, as were key circulating SASP factors, compared to before administration of these senolytic drugs [3].”

Ronald Kohanski, deputy director of the division of aging biology at the National Institute of Aging also found the results encouraging. “The demonstration that senescent cell numbers can be reduced in two tissues in humans is an important advance based on the compelling evidence from studies in laboratory mice,” he said [4].

Being able to target and destroy senescent cells could be an important treatment for Alzheimer’s and Parkinson’s disease, as research has previously demonstrated [5],  not to mention furthering our knowledge of aging and how to tackle it.

However, the study authors are aware that DQ as a therapy in humans is still in the early stages of research. “The field of senolytics is new. The first clinical trial of senolytic agents was only reported in January 2019,” the authors state.

“The findings reported here are preliminary results from an ongoing clinical trial of senolytics for treating dysfunction in patients with diabetic chronic kidney disease. Fewer than 150 subjects have been treated with these drugs in the context of clinical trials that we are aware of so far … We caution against the use of senolytic agents outside the context of clinical trials until more is known about their effects and side effects [6].”

[1] https://bit.ly/2CVQKdL
[2] https://bit.ly/3glWbQN
[3] Ibid
[4] https://mayocl.in/2Yt5WXe
[5] https://bit.ly/3aSZ6iL
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6796530/

Image credit: Gil C / Shutterstock
Eleanor Garth
Deputy Editor Now a science and medicine journalist, Eleanor worked as a consultant for university spin-out companies and provided research support at Imperial College London and various London hospitals in a former life.

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

Printers that can now print DNA

DNA Script obtains CE Mark for SYNTAX DNA printing platform. DNA Script, a leader in Enzymatic DNA Synthesis (EDS), announced the CE marking of its SYNTAX System, the...

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...

    Subscribe to our newsletter