A senolytic (from the words ''
senescence
Senescence () or biological aging is the gradual deterioration of functional characteristics in living organisms. The word ''senescence'' can refer to either cellular senescence or to senescence of the whole organism. Organismal senescence inv ...
'' and ''-lytic'', "destroying") is among a class of
small molecule
Within the fields of molecular biology and pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000 daltons) organic compound that may regulate a biological process, with a size on the order of 1 nm. Many drugs ar ...
s under
basic research
Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied resear ...
to determine if they can selectively induce death of
senescent cells
Cellular senescence is a phenomenon characterized by the cessation of cell division. In their experiments during the early 1960s, Leonard Hayflick and Paul Moorhead found that normal human fetal fibroblasts in culture reach a maximum of approxi ...
and improve health in humans.
A goal of this research is to discover or develop agents to delay, prevent, alleviate, or reverse age-related diseases.
A related concept is "senostatic", which means to suppress senescence.
Research
Possible senolytic agents are under preliminary research, including some which are in
early-stage human trials.
The majority of candidate senolytic compounds are repurposed
anti-cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal ble ...
molecules, such as the
chemotherapeutic
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs ( chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemothera ...
drug
dasatinib
Dasatinib, sold under the brand name Sprycel among others, is a targeted therapy medication used to treat certain cases of chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). Specifically it is used to treat cases that ar ...
and the experimental small molecule
navitoclax
Navitoclax (previously ABT-263) is an experimental orally active anti-cancer drug, which is a Bcl-2 inhibitor similar in action to obatoclax.
Mechanism of action
Navitoclax inhibits not only Bcl-2, but also Bcl-XL and Bcl-w proteins. Beca ...
.
According to reviews, it is thought that senolytics can be administered intermittently while being as effective as continuous administration. This could be an advantage of senolytic drugs and decrease adverse effects, for instance circumventing potential off-target effects.
Senolytic candidates
Senomorphics
Senolytics
eliminate senescent cells whereas
senomorphics – with candidates such as
Apigenin
Apigenin (4′,5,7-trihydroxyflavone), found in many plants, is a natural product belonging to the flavone class that is the aglycone of several naturally occurring glycosides. It is a yellow crystalline solid that has been used to dye wool.
S ...
,
Rapamycin
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, ...
and
rapalog Everolimus – modulate properties of senescent cells without eliminating them, suppressing phenotypes of senescence, including the
SASP.
See also
*
Autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
*
Biogerontology
Biogerontology is the sub-field of gerontology concerned with the biological aging process, its evolutionary origins, and potential means to intervene in the process. The term "biogerontology" was coined by S. Rattan, and came in regular use wit ...
*
DNA repair#Senescence and apoptosis
*
Geroprotector
*
Hsp90
Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...
*
Immunosenescence
Immunosenescence is the gradual deterioration of the immune system, brought on by natural age advancement. A 2020 review concluded that the adaptive immune system is affected more than the innate immune system. Immunosenescence involves both the ...
*
Invariant NKT (iNKT) cells
*
Klotho (biology)#Effects on aging
*
Life extension
Life extension is the concept of extending the human life expectancy, lifespan, either modestly through improvements in medicine or dramatically by increasing the maximum lifespan beyond its generally-settled oldest people, limit of 125 years.
S ...
*
Senescence-associated beta-galactosidase
Senescence-associated beta-galactosidase (SA-β-gal or SABG) is a hypothetical hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides only in senescent cells. Senescence-associated beta-galactosidase, along with ...
, used as a biomarker
*
Senotherapy
Senotherapy is an early-stage basic research field for development of possible therapeutic agents and strategies to specifically target cellular senescence, an altered cell state associated with ageing and age-related diseases. The name derives fr ...
*
Sirtuin-activating compound
Sirtuin-activating compounds (STAC) are chemical compounds having an effect on sirtuins, a group of enzymes that use NAD+ to remove acetyl groups from proteins. They are caloric restriction mimetic compounds that may be helpful in treating various ...
*
Unity Biotechnology
Unity Biotechnology is a publicly traded American biotechnology company that develops drugs that target senescent cells.
The company's products in development include UBX 1325, which targets Bcl-xL, a mechanism to eliminate senescent cells in a ...
*
Venetoclax
Venetoclax, sold under the brand names Venclexta and Venclyxto, is a medication used to treat adults with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or acute myeloid leukemia (AML).
The most common side effects are l ...
*
YPEL3#Cellular senescence
References
External links
*
* , a review that is
open access
Open access (OA) is a set of principles and a range of practices through which research outputs are distributed online, free of access charges or other barriers. With open access strictly defined (according to the 2001 definition), or libre op ...
and features a list of senolytics candidates
*
* {{Cite journal , last=Dance , first=Amber , date=2022-12-21 , title=Could getting rid of old cells turn back the clock on aging? , url=https://knowablemagazine.org/article/health-disease/2022/could-getting-rid-old-cells-turn-back-clock-aging?mc_cid=b691ff690b&mc_eid=6e7303fddd , journal=Knowable Magazine {{! Annual Reviews , language=en , doi=10.1146/knowable-122122-1, s2cid=255055238
Senescence in non-human organisms
Senescence
Anti-aging substances