Skip to main content
Log in

Potential Geroprotectors – From Bench to Clinic

  • REVIEW
  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

Geroprotectors are substances that slow down aging process and can be used for prevention of age-related diseases. Geroprotectors can improve functioning of various organ systems and enhance their homeostatic capabilities. We have developed a system of criteria for geroprotectors and proposed their classification based on the mechanisms of their action on the aging processes. Geroprotectors are required to reduce mortality, improve human aging biomarkers, have minimal side effects, and enhance quality of life. Additionally, there are approaches based on combining geroprotectors targeted to different targets and mechanisms of aging to achieve maximum effectiveness. Currently, numerous preclinical studies are being conducted to identify new molecular targets and develop new approaches to extend healthy aging, although the number of clinical trials is limited. Geroprotectors have the potential to become a new class of preventive medicines as they prevent onset of certain diseases or slow down their progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Fomenko, A. M., Proshkina, E. N., Fedintsev, A. Yu., Tsvetkov, V. O., Shaposhnikiv, M. V., and Moskalev, A. A. (2016) Potential Geroprotectors, Evropeisky Dom, St.-Petersburg.

  2. Bischof, E., Scheibye-Knudsen, M., Siow, R., and Moskalev, A. (2021) Longevity medicine: upskilling the physicians of tomorrow, Lancet Healthy Longev., 2, e187-e188, https://doi.org/10.1016/S2666-7568(21)00024-6.

    Article  PubMed  Google Scholar 

  3. Moskalev, A., Chernyagina, E., Tsvetkov, V., Fedintsev, A., Shaposhnikov, M., Krut’ko, V., Zhavoronkov, A., and Kennedy, B. K. (2016) Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic, Aging Cell, 15, 407-415, https://doi.org/10.1111/acel.12463.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Moskalev, A., Chernyagina, E., de Magalhaes, J. P., Barardo, D., Thoppil, H., Shaposhnikov, M., Budovsky, A., Fraifeld, V. E., Garazha, A., Tsvetkov, V., Bronovitsky, E., Bogomolov, V., Scerbacov, A., Kuryan, O., Gurinovich, R., Jellen, L. C., Kennedy, B., Mamoshina, P., Dobrovolskaya, E., Aliper, A., et al. (2015) Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease, Aging (Albany NY), 7, 616-628, https://doi.org/10.18632/aging.100799.

    Article  CAS  PubMed  Google Scholar 

  5. Barardo, D., Thornton, D., Thoppil, H., Walsh, M., Sharifi, S., Ferreira, S., Anzic, A., Fernandes, M., Monteiro, P., Grum, T., Cordeiro, R., De-Souza, E. A., Budovsky, A., Araujo, N., Gruber, J., Petrascheck, M., Fraifeld, V. E., Zhavoronkov, A., Moskalev, A., and de Magalhaes, J. P. (2017) The DrugAge database of aging-related drugs, Aging Cell, 16, 594-597, https://doi.org/10.1111/acel.12585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Dilman, V. M. (1986) The Grand Biological Clock. Introduction to Integral Medicine [in Russian], Znaniye, Moscow.

  7. Blagosklonny, M. V. (2009) TOR-driven aging: speeding car without brakes, Cell Cycle, 8, 4055-4059, https://doi.org/10.4161/cc.8.24.10310.

    Article  CAS  PubMed  Google Scholar 

  8. Moskalev, A. (2020) The challenges of estimating biological age, Elife, 9, e54969, https://doi.org/10.7554/eLife.54969.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Maganova, F., Voevoda, M., Popov, V., and Moskalev, A. (2023) A prospective randomized comparative placebo-controlled double-blind study in two groups to assess the effect of the use of biologically active additives with Siberian fir terpenes for the biological age of a person, Front. Pharmacol., 14, 1150504, https://doi.org/10.3389/fphar.2023.1150504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Proshkina, E., Plyusnin, S., Babak, T., Lashmanova, E., Maganova, F., Koval, L., Platonova, E., Shaposhnikov, M., and Moskalev, A. (2020) Terpenoids as potential geroprotectors, Antioxidants (Basel), 9, 529, https://doi.org/10.3390/antiox9060529.

    Article  CAS  PubMed  Google Scholar 

  11. Proshkina, E., Shaposhnikov, M., and Moskalev, A. (2020) Genome-protecting compounds as potential geroprotectors, Int. J. Mol. Sci., 21, 4484, https://doi.org/10.3390/ijms21124484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Anisimov, V. N. (2001) Life span extension and cancer risk: myths and reality, Exp. Gerontol., 36, 1101-1136, https://doi.org/10.1016/s0531-5565(01)00114-0.

    Article  CAS  PubMed  Google Scholar 

  13. Moskalev, A., Chernyagina, E., Kudryavtseva, A., and Shaposhnikov, M. (2017) Geroprotectors: a unified concept and screening approaches, Aging Dis., 8, 354-363, https://doi.org/10.14336/AD.2016.1022.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Araldi, E., Jutzeler, C. R., and Ristow, M. (2023) Effects of antidiabetic drugs on mortality risks in individuals with type 2 diabetes: A prospective cohort study of UK Biobank participants, medRxiv, https://doi.org/10.1101/2023.05.19.23290214.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Roussel, R., Travert, F., Pasquet, B., Wilson, P. W., Smith, S. C., Jr., Goto, S., Ravaud, P., Marre, M., Porath, A., Bhatt, D. L., Steg, P. G., and Reduction of Atherothrombosis for Continued Health Registry Investigators (2010) Metformin use and mortality among patients with diabetes and atherothrombosis, Arch. Intern. Med., 170, 1892-1899, https://doi.org/10.1001/archinternmed.2010.409.

    Article  CAS  PubMed  Google Scholar 

  16. Bergman, J., Nordstrom, A., Hommel, A., Kivipelto, M., and Nordstrom, P. (2019) Bisphosphonates and mortality: confounding in observational studies? Osteoporos. Int., 30, 1973-1982, https://doi.org/10.1007/s00198-019-05097-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Gitsels, L. A., Bakbergenuly, I., Steel, N., and Kulinskaya, E. (2021) Do statins reduce mortality in older people? Findings from a longitudinal study using primary care records, Fam. Med. Community Health, 9, e000780, https://doi.org/10.1136/fmch-2020-000780.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Moskalev, A. A., Aliper, A. M., Smit-McBride, Z., Buzdin, A., and Zhavoronkov, A. (2014) Genetics and epigenetics of aging and longevity, Cell Cycle, 13, 1063-1077, https://doi.org/10.4161/cc.28433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Calabrese, E. J. (2013) Hormesis: toxicological foundations and role in aging research, Exp. Gerontol., 48, 99-102, https://doi.org/10.1016/j.exger.2012.02.004.

    Article  CAS  PubMed  Google Scholar 

  20. Rattan, S. I. (2012) Rationale and methods of discovering hormetins as drugs for healthy ageing, Expert Opin. Drug Discov., 7, 439-448, https://doi.org/10.1517/17460441.2012.677430.

    Article  CAS  PubMed  Google Scholar 

  21. Blagosklonny, M. V. (2014) Geroconversion: irreversible step to cellular senescence, Cell Cycle, 13, 3628-3635, https://doi.org/10.4161/15384101.2014.985507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Franceschi, C. (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr. Rev., 65, S173-S176, https://doi.org/10.1111/j.1753-4887.2007.tb00358.x.

    Article  PubMed  Google Scholar 

  23. Moskalev, A., Guvatova, Z., Lopes, I. A., Beckett, C. W., Kennedy, B. K., De Magalhaes, J. P., and Makarov, A. A. (2022) Targeting aging mechanisms: pharmacological perspectives, Trends Endocrinol. Metab., 33, 266-280, https://doi.org/10.1016/j.tem.2022.01.007.

    Article  CAS  PubMed  Google Scholar 

  24. Zhavoronkov, A., Buzdin, A. A., Garazha, A. V., Borisov, N. M., and Moskalev, A. A. (2014) Signaling pathway cloud regulation for in silico screening and ranking of the potential geroprotective drugs, Front. Genet., 5, 49, https://doi.org/10.3389/fgene.2014.00049.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yang, J., Peng, S., Zhang, B., Houten, S., Schadt, E., Zhu, J., Suh, Y., and Tu, Z. (2020) Human geroprotector discovery by targeting the converging subnetworks of aging and age-related diseases, Geroscience, 42, 353-372, https://doi.org/10.1007/s11357-019-00106-x.

    Article  CAS  PubMed  Google Scholar 

  26. Pun, F. W., Leung, G. H. D., Leung, H. W., Liu, B. H. M., Long, X., Ozerov, I. V., Wang, J., Ren, F., Aliper, A., Izumchenko, E., Moskalev, A., de Magalhaes, J. P., and Zhavoronkov, A. (2022) Hallmarks of aging-based dual-purpose disease and age-associated targets predicted using PandaOmics AI-powered discovery engine, Aging (Albany NY), 14, 2475-2506, https://doi.org/10.18632/aging.203960.

    Article  CAS  PubMed  Google Scholar 

  27. Danilov, A., Shaposhnikov, M., Plyusnina, E., Kogan, V., Fedichev, P., and Moskalev, A. (2013) Selective anticancer agents suppress aging in Drosophila, Oncotarget, 4, 1507-1526, https://doi.org/10.18632/oncotarget.1272.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Admasu, T. D., Chaithanya Batchu, K., Barardo, D., Ng, L. F., Lam, V. Y. M., Xiao, L., Cazenave-Gassiot, A., Wenk, M. R., Tolwinski, N. S., and Gruber, J. (2018) Drug synergy slows aging and improves healthspan through IGF and SREBP lipid signaling, Dev. Cell, 47, 67-79.e65, https://doi.org/10.1016/j.devcel.2018.09.001.

    Article  CAS  PubMed  Google Scholar 

  29. Mehdipour, M., Etienne, J., Chen, C. C., Gathwala, R., Rehman, M., Kato, C., Liu, C., Liu, Y., Zuo, Y., Conboy, M. J., and Conboy, I. M. (2019) Rejuvenation of brain, liver and muscle by simultaneous pharmacological modulation of two signaling determinants, that change in opposite directions with age, Aging (Albany NY), 11, 5628-5645, https://doi.org/10.18632/aging.102148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fahy, G. M., Brooke, R. T., Watson, J. P., Good, Z., Vasanawala, S. S., Maecker, H., Leipold, M. D., Lin, D. T. S., Kobor, M. S., and Horvath, S. (2019) Reversal of epigenetic aging and immunosenescent trends in humans, Aging Cell, 18, e13028, https://doi.org/10.1111/acel.13028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Moskalev, A. (2020) Is anti-ageing drug discovery becoming a reality, Expert Opin. Drug Discov., 15, 135-138, https://doi.org/10.1080/17460441.2020.1702965.

    Article  PubMed  Google Scholar 

  32. Mannick, J. B., Teo, G., Bernardo, P., Quinn, D., Russell, K., Klickstein, L., Marshall, W., and Shergill, S. (2021) Targeting the biology of ageing with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomised trials, Lancet Healthy Longev., 2, e250-e262, https://doi.org/10.1016/S2666-7568(21)00062-3.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Dihoum, A., Rena, G., Pearson, E. R., Lang, C. C., and Mordi, I. R. (2023) Metformin: evidence from preclinical and clinical studies for potential novel applications in cardiovascular disease, Expert Opin. Invest. Drugs, 32, 291-299, https://doi.org/10.1080/13543784.2023.2196010.

    Article  CAS  Google Scholar 

  34. Ghazizadeh-Hashemi, F., Bagheri, S., Ashraf-Ganjouei, A., Moradi, K., Shahmansouri, N., Mehrpooya, M., Noorbala, A. A., and Akhondzadeh, S. (2021) Efficacy and safety of sulforaphane for treatment of mild to moderate depression in patients with history of cardiac interventions: A randomized, double-blind, placebo-controlled clinical trial, Psychiatry Clin. Neurosci., 75, 250-255, https://doi.org/10.1111/pcn.13276.

    Article  CAS  PubMed  Google Scholar 

  35. Zhong, O., Wang, J., Tan, Y., Lei, X., and Tang, Z. (2022) Effects of NAD+ precursor supplementation on glucose and lipid metabolism in humans: a meta-analysis, Nutr. Metab. (Lond), 19, 20, https://doi.org/10.1186/s12986-022-00653-9.

    Article  CAS  PubMed  Google Scholar 

  36. Islam, M. T., Tuday, E., Allen, S., Kim, J., Trott, D. W., Holland, W. L., Donato, A. J., and Lesniewski, L. A. (2023) Senolytic drugs, dasatinib and quercetin, attenuate adipose tissue inflammation, and ameliorate metabolic function in old age, Aging Cell, 22, e13767, https://doi.org/10.1111/acel.13767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

The author is grateful to his colleagues and collaborators participating in our studies of geroprotectors cited in this review.

Funding

This work was financially supported by the Program “Prioritet 2030” of the Nizny Novgorod State University “Healthy Generation”.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Alexey A. Moskalev.

Ethics declarations

The author declares no conflict of interests in financial or any other sphere. This article does not contain any studies with human participants or animals performed by the author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moskalev, A.A. Potential Geroprotectors – From Bench to Clinic. Biochemistry Moscow 88, 1732–1738 (2023). https://doi.org/10.1134/S0006297923110056

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297923110056

Keywords

Navigation