Targeting aging mechanisms: pharmacological perspectives
Authors: Zulfiya Guvatova
Charles W Beckett
Alexey Moskalev
Joao Pedro De Magalhaes
Brian K Kennedy
Ines De Almeida Lopes
Alexander A Makarov
Journal: Trends in Endocrinology and Metabolism (2022)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: anti-aging; antioxidant; geroprotector; hormetin; senolytic
Affiliations: Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia; Institute of Biology of the Federal Research Center of Komi Science Center, Ural Branch of the Russian Academy of Sciences, 28 Kommunisticheskaya Street, Syktyvkar 167982, Russia. Electronic address: ., Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia., Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK., Healthy Longevity Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Centre for Healthy Longevity, National University Health System, Singapore; Singapore Institute of Clinical Sciences, A*STAR, Singapore., Integrative Genomics of Ageing Group, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool L7 8TX, UK. Electronic address: ., Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow 119991, Russia. Electronic address: .

Abstract:  Geroprotectors slow down aging and promote healthy longevity in model animals. Although hundreds of compounds have been shown to extend the life of laboratory model organisms, clinical studies on potential geroprotectors are exceedingly rare, especially in healthy elders. This review aims to classify potential geroprotectors based on the mechanisms by which they influence aging. These pharmacological interventions can be classified into the following groups: those that prevent oxidation; proteostasis regulators; suppressors of genomic instability; epigenetic drugs; those that preserve mitochondrial function; inhibitors of aging-associated signaling pathways; hormetins; senolytics/senostatics; anti-inflammatory drugs; antifibrotic agents; neurotrophic factors; factors preventing the impairment of barrier function; immunomodulators; and prebiotics, metabiotics, and enterosorbents. 

Retracted: No

PubPeer comments:
 Pharmacological management of aging is a viable topic. However, the analysis provided here is quite limited. DrugAge and Geroprotectors databases are mentioned, but only DrugAge is analyzed in the article. Authors mention use of R, but did not take the advantage of its data processing abilities. Also, statistical significance intentionally did not taken into account , and it is still debatable if the size of the effect was considered instead, but it was not. The spread of the magnitude of the effects is estimated without taking into account doses and species - this is highly doubtful approach from the pharmacological point of view. The rest of the review is a compilation of lit. data on various mechanisms of aging without analysis and critical evaluation. Classification in Table 1 is rather a list of gerosuppression mechanisms from molecular to systemic level, although it is obvious that the effect at a higher level is always a consequence of molecular interactions. That is, all this division is largely arbitrary and only says that we do not always know a specific target. One cannot classify geroprotectors in this way, these are just manifestations of their effects at different levels of the organization of living matter. If instead the analysis of known targets were performed for agents with a reliable effect, and targets pathways were correlated with effect size, the work might be of much greater value. ,