Researchers have demonstrated that nanoparticles coated with quercetin
molecules can selectively target and eliminate harmful senescent cells.
As you age, increasing numbers of your cells enter into a state known as
senescence. Senescent cells do not divide or support the tissues of
which they are part; instead, they emit a range of potentially harmful
chemical signals that encourage nearby healthy cells to enter the same
senescent state. Their presence causes many problems: they reduce tissue
repair, increase chronic inflammation, and can even eventually raise
the risk of cancer and other age-related diseases.
wisepoqder Quercetin powder
Senescent cells normally destroy themselves via a programmed process
called apoptosis, and they are also removed by the immune system;
however, the immune system weakens with age, and increasing numbers of
senescent cells escape this process and begin to accumulate in all the
tissues of the body.
By the time people reach old age, significant numbers of these senescent
cells have built up, causing chronic inflammation and damage to
surrounding cells and tissue. These senescent cells are a key process in
the progression of aging.
Senescent cells only make up a small number of total cells in the body,
but they secrete pro-inflammatory cytokines, chemokines, and
extracellular matrix proteases, which, together, form the
senescence-associated secretory phenotype, or SASP. The SASP is thought
to significantly contribute to aging and cancer; thus, targeting
senescent cells and removing them has been suggested as a potential
solution to this problem.
The trouble with quercetin
Quercetin is a naturally occurring plant polyphenol, a category that
often has poor water solubility, chemical instability, or poor
bioavailability. These confounding factors could be muddling its
effectiveness and making it unreliable as a senolytic therapy. This
likely explains why different senolytic studies using quercetin have
yielded conflicting results: there are simply too many processes that
can influence these natural molecules for them to be reliable.
We have seen in past mouse studies and recent Mayo Clinic human trials
that quercetin, when used in combination with the cancer drug dasatinib,
can be the basis for an effective therapy for eliminating senescent
cells. Unfortunately, on its own, quercetin does not have a significant
senolytic effect, which is possibly due to its limitations as a
polyphenol.
However, there are ways to overcome these issues with quercetin and
other similar polyphenols, and that is by using special delivery systems
that make the molecules more effective and controllable. Polymer
nanoparticles, lipid-based carriers, inclusion complexes, micelles, and
conjugate-based delivery systems are all examples of approaches that can
deliver molecules more effectively.
Nanoparticles make quercetin more effective
The researchers of this study opted to use a nanoparticle-based delivery
system to carry quercetin molecules to senescent cells in order to
destroy them [1]. They created magnetite nanoparticles and coated their
surface with quercetin molecules, then examined the senolytic action of
this approach.
They found that the nanoparticles were effective at attenuating
inflammatory signals, such as interleukin 8 and interferon beta, which
are secreted by senescent cells. They also found that cells forced into
early senescence via stress were destroyed by the nanoparticles and that
the secretion of inflammatory signals was reduced.Doing this also led
to an elevated activity of AMP-activated protein kinase (AMPK). This is a
critical nutrient and energy sensing enzyme that is present in all
mammalian cells and maintains energy homeostasis. When activated, it
facilitates energy-generating processes, such as glucose uptake and
fatty acid oxidation, and decreases energy-consuming processes, such as
protein and lipid synthesis. AMPK is one of the four pathways that
control our metabolism, and its deregulation is a proposed reason why we
age and develop metabolic conditions such as type 2 diabetes.
Cellular senescence may contribute to aging and age-related diseases and
senolytic drugs that selectively kill senescent cells may delay aging
and promote healthspan. More recently, several categories of senolytics
have been established, namely HSP90 inhibitors, Bcl-2 family inhibitors
and natural compounds such as quercetin and fisetin. However, senolytic
and senostatic potential of nanoparticles and surface-modified
nanoparticles has never been addressed. In the present study, quercetin
surface functionalized Fe3O4 nanoparticles (MNPQ) were synthesized and
their senolytic and senostatic activity was evaluated during oxidative
stress-induced senescence in human fibroblasts in vitro. MNPQ promoted
AMPK activity that was accompanied by non-apoptotic cell death and
decreased number of stress-induced senescent cells (senolytic action)
and the suppression of senescence-associated proinflammatory response
(decreased levels of secreted IL-8 and IFN-ß, senostatic action). In
summary, we have shown for the first time that MNPQ may be considered as
promising candidates for senolytic- and senostatic-based anti-aging
therapies.
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