Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Apr 4;11(7):1222.
doi: 10.3390/cells11071222.

Senotherapeutics in Cancer and HIV

Laura Sánchez-Díaz  1   2 , Asunción Espinosa-Sánchez  1   2 , José-Ramón Blanco  3 , Amancio Carnero  1   2
Affiliations
Review

Senotherapeutics in Cancer and HIV

Laura Sánchez-Díaz et al. Cells. .

Abstract

Cellular senescence is a stress-response mechanism that contributes to homeostasis maintenance, playing a beneficial role during embryogenesis and in normal adult organisms. In contrast, chronic senescence activation may be responsible for other events such as age-related disorders, HIV and cancer development. Cellular senescence activation can be triggered by different insults. Regardless of the inducer, there are several phenotypes generally shared among senescent cells: cell division arrest, an aberrant shape, increased size, high granularity because of increased numbers of lysosomes and vacuoles, apoptosis resistance, defective metabolism and some chromatin alterations. Senescent cells constitute an important area for research due to their contributions to the pathogenesis of different diseases such as frailty, sarcopenia and aging-related diseases, including cancer and HIV infection, which show an accelerated aging. Hence, a new pharmacological category of treatments called senotherapeutics is under development. This group includes senolytic drugs that selectively attack senescent cells and senostatic drugs that suppress SASP factor delivery, inhibiting senescent cell development. These new drugs can have positive therapeutic effects on aging-related disorders and act in cancer as antitumor drugs, avoiding the undesired effects of senescent cells such as those from SASP. Here, we review senotherapeutics and how they might affect cancer and HIV disease, two very different aging-related diseases, and review some compounds acting as senolytics in clinical trials.

Keywords: HIV; SASP; cancer; senescence; senolytic; senostatic; senotherapy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that this research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.

Figures

Figure 1
Figure 1
Characteristics, advantages and disadvantages of cellular senescence. Note: COPD: chronic obstructive pulmonary disease; SAHF: senescence-associated heterochromatin foci; SASP: Senescence-associated secretory phenotype.
Figure 2
Figure 2
Induction of senescence by the anticancer treatment of tumor cells and the effects of senescent cells and secreted SASP in cancer. Senotherapies in cancer try to remove chemotherapy-induced senescent cells and/or block deleterious SASP.
Figure 3
Figure 3
Scheme of senotherapeutics as a new pharmacological category of treatments.
Figure 4
Figure 4
Main causes and consequences of HIV aging.
See this image and copyright information in PMC

References

    1. Hayflick L., Moorhead P.S. The serial cultivation of human diploid cell strains. Exp. Cell Res. 1961;25:585–621. doi: 10.1016/0014-4827(61)90192-6. - DOI - PubMed
    1. Harley C.B., Futcher A.B., Greider C.W. Telomeres shorten during ageing of human fibroblasts. Nature. 1990;345:458–460. doi: 10.1038/345458a0. - DOI - PubMed
    1. Olovnikov A. A theory of marginotomy: The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon. J. Theor. Biol. 1973;41:181–190. doi: 10.1016/0022-5193(73)90198-7. - DOI - PubMed
    1. Shay J.W., Wright W.E. Hallmarks of telomeres in ageing research. J. Pathol. 2007;211:114–123. doi: 10.1002/path.2090. - DOI - PubMed
    1. Bodnar A.G., Ouellette M., Frolkis M., Holt S.E., Chiu C.-P., Morin G.B., Harley C.B., Shay J.W., Lichtsteiner S., Wright W.E. Extension of Life-Span by Introduction of Telomerase into Normal Human Cells. Science. 1998;279:349–352. doi: 10.1126/science.279.5349.349. - DOI - PubMed

Publication types

Substances