Evidence map›Paper›PMID 27677171›Full record

ArticleAging2016

In search for geroprotectors: in silico screening and in vitro validation of signalome-level mimetics of young healthy state.

Alexander Aliper, Aleksey V Belikov, Andrew Garazha, Leslie Jellen, Artem Artemov, Maria Suntsova, Alena Ivanova, Larisa Venkova, Nicolas Borisov, Anton Buzdin and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed.

  1. Review
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  11. Aging delay: of mice and men.Acta bio-medica : Atenei Parmensis · 2021
    Article
  12. Article
  13. Article
  14. The Resistance ofAntioxidants (Basel, Switzerland) · 2020
    Article
  15. Article
  16. The quest to slow ageing through drug discovery.Nature reviews. Drug discovery · 2020
    Review
  17. Review
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Alexander AliperInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Aleksey V BelikovMoscow Institute of Physics and Technology, Dolgoprudny, 141700, Russia.
Andrew GarazhaInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Leslie JellenInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Artem ArtemovInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Maria SuntsovaD. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology, and Immunology, Moscow, 117997, Russia.
Alena IvanovaD. Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology, and Immunology, Moscow, 117997, Russia.
Larisa VenkovaInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Nicolas BorisovInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Anton BuzdinPathway Pharmaceuticals, Ltd, Hong Kong, Hong Kong.
Polina MamoshinaInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Eugene LaneInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Andrew G SwickLife Extension, Ft. Lauderdale, FL 33308, USA.
Alexey MoskalevInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.
Alex ZhavoronkovInsilico Medicine, Inc, Research Department, Baltimore, MD 21218, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Populations in developed nations throughout the world are rapidly aging, and the search for geroprotectors, or anti-aging interventions, has never been more important. Yet while hundreds of geroprotectors have extended lifespan in animal models, none have yet been approved for widespread use in humans. GeroScope is a computational tool that can aid prediction of novel geroprotectors from existing human gene expression data. GeroScope maps expression differences between samples from young and old subjects to aging-related signaling pathways, then profiles pathway activation strength (PAS) for each condition. Known substances are then screened and ranked for those most likely to target differential pathways and mimic the young signalome. Here we used GeroScope and shortlisted ten substances, all of which have lifespan-extending effects in animal models, and tested 6 of them for geroprotective effects in senescent human fibroblast cultures. PD-98059, a highly selective MEK1 inhibitor, showed both life-prolonging and rejuvenating effects. Natural compounds like N-acetyl-L-cysteine, Myricetin and Epigallocatechin gallate also improved several senescence-associated properties and were further investigated with pathway analysis. This work not only highlights several potential geroprotectors for further study, but also serves as a proof-of-concept for GeroScope, Oncofinder and other PAS-based methods in streamlining drug prediction, repurposing and personalized medicine.

Indexed as

Computer SimulationAgingAnimalsHumansLongevityagingdrug discoverydrug repurposinggeroprotectorscreening

Identifiers

PMID27677171
PMCPMC5076455

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.