Literature DB >> 30973028

Drugs that target aging: how do we discover them?

A Myers1,2, G J Lithgow1.   

Abstract

INTRODUCTION: Biology of aging is focused on elucidating the biochemical and genetic pathways that contribute to cellular damage accumulation over time. Thirty years of research are beginning to bear fruit as the first pharmacological interventions based on biology of aging go through clinical trials. Evolutionary theories of aging suggest that naturally selected traits believed to impart fitness in young organisms may be damaging in later life. Three major areas of focus in biology of aging are lifespan, healthspan, and rejuvenation. Areas covered: Aging research has produced several validated pharmacological interventions currently in clinical trials. Herein, the authors consider two representative case studies: 1) rapamycin analogs and their effect on the mTORC1 pathway, and 2) small molecules that target and kill senescent cells. The authors also provide their expert current and future perspectives on aging targeting drug discovery. Expert opinion: Aging-related therapeutic interventions will continue to emerge at an accelerating pace, both from research in biology of aging, as well as from coordinated biomedical research in aging-related chronic conditions.

Entities:  

Keywords:  Age-related; aging; drug discovery; geroscience; healthspan; lifespan; longevity; rapamycin; rejuvenation; senolytics

Mesh:

Substances:

Year:  2019        PMID: 30973028      PMCID: PMC6497572          DOI: 10.1080/17460441.2019.1597049

Source DB:  PubMed          Journal:  Expert Opin Drug Discov        ISSN: 1746-0441            Impact factor:   6.098


  44 in total

1.  Genetics: influence of TOR kinase on lifespan in C. elegans.

Authors:  Tibor Vellai; Krisztina Takacs-Vellai; Yue Zhang; Attila L Kovacs; László Orosz; Fritz Müller
Journal:  Nature       Date:  2003-12-11       Impact factor: 49.962

2.  THE LIMITED IN VITRO LIFETIME OF HUMAN DIPLOID CELL STRAINS.

Authors:  L HAYFLICK
Journal:  Exp Cell Res       Date:  1965-03       Impact factor: 3.905

3.  The serial cultivation of human diploid cell strains.

Authors:  L HAYFLICK; P S MOORHEAD
Journal:  Exp Cell Res       Date:  1961-12       Impact factor: 3.905

4.  Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients.

Authors:  Matt Kaeberlein; R Wilson Powers; Kristan K Steffen; Eric A Westman; Di Hu; Nick Dang; Emily O Kerr; Kathryn T Kirkland; Stanley Fields; Brian K Kennedy
Journal:  Science       Date:  2005-11-18       Impact factor: 47.728

5.  Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle.

Authors:  C Vézina; A Kudelski; S N Sehgal
Journal:  J Antibiot (Tokyo)       Date:  1975-10       Impact factor: 2.649

6.  Senescent fibroblasts promote epithelial cell growth and tumorigenesis: a link between cancer and aging.

Authors:  A Krtolica; S Parrinello; S Lockett; P Y Desprez; J Campisi
Journal:  Proc Natl Acad Sci U S A       Date:  2001-10-02       Impact factor: 11.205

Review 7.  Senescent cells, tumor suppression, and organismal aging: good citizens, bad neighbors.

Authors:  Judith Campisi
Journal:  Cell       Date:  2005-02-25       Impact factor: 41.582

8.  Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast.

Authors:  J Heitman; N R Movva; M N Hall
Journal:  Science       Date:  1991-08-23       Impact factor: 47.728

Review 9.  The molecular target of rapamycin (mTOR) as a therapeutic target against cancer.

Authors:  Monica M Mita; Alain Mita; Eric K Rowinsky
Journal:  Cancer Biol Ther       Date:  2003 Jul-Aug       Impact factor: 4.742

10.  Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway.

Authors:  Pankaj Kapahi; Brian M Zid; Tony Harper; Daniel Koslover; Viveca Sapin; Seymour Benzer
Journal:  Curr Biol       Date:  2004-05-25       Impact factor: 10.834

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  4 in total

Review 1.  Nanodelivery of phytobioactive compounds for treating aging-associated disorders.

Authors:  Oleh Lushchak; Olha Strilbytska; Alexander Koliada; Alina Zayachkivska; Nadia Burdyliuk; Ihor Yurkevych; Kenneth B Storey; Alexander Vaiserman
Journal:  Geroscience       Date:  2019-11-04       Impact factor: 7.713

Review 2.  Phenotypic Screening in C. elegans as a Tool for the Discovery of New Geroprotective Drugs.

Authors:  Sven Bulterijs; Bart P Braeckman
Journal:  Pharmaceuticals (Basel)       Date:  2020-07-25

3.  Pterocarpus marsupium extract extends replicative lifespan in budding yeast.

Authors:  Mitchell B Lee; Michael G Kiflezghi; Mitsuhiro Tsuchiya; Brian Wasko; Daniel T Carr; Priya A Uppal; Katherine A Grayden; Yordanos C Elala; Tu Anh Nguyen; Jesse Wang; Priya Ragosti; Sunny Nguyen; Yan Ting Zhao; Deborah Kim; Socheata Thon; Irika Sinha; Thao T Tang; Ngoc H B Tran; Thu H B Tran; Margarete D Moore; Mary Ann K Li; Karl Rodriguez; Daniel E L Promislow; Matt Kaeberlein
Journal:  Geroscience       Date:  2021-07-23       Impact factor: 7.713

4.  A Geroscience Perspective on COVID-19 Mortality.

Authors:  Daniel E L Promislow
Journal:  J Gerontol A Biol Sci Med Sci       Date:  2020-09-16       Impact factor: 6.053

  4 in total

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