Cellular senescence is an altered cell state associated with permanent
cell cycle arrest and an immunogenic, pro-inflammatory secretome that can
contribute to the development and progression of age-related diseases. Because cellular senescence can occur in
different cell types (i.e. pancreatic beta cells, vascular smooth muscle cells,
astrocytes) that undertake different biological functions, then their
appearance can manifest differently and we refer to these manifestations as
different diseases. These include, diabetes,
cardiovascular disease, COPD and cancer.
The mechanisms by which senescent cells can cause disease include:
(1) Loss
of cellular regenerative capacity.
(2) Loss
of normal cell function.
(3) Persistent
pro-inflammatory tissue damage.
(4) Altering
the behaviour of neighbouring cells.
(5) Protease-mediated
degradation of extracellular structural proteins.
Although scientists researching cell senescence have long
suspected that senescent cells play an important role in ageing and age-related
disease, convincing evidence had not been provided until 2011 when Scientists
from the Mayo Clinic in the US published their findings on the elimination of
senescent cells in mice. The
elimination of senescent cells using transgenic (genetically engineered) mice
delayed the onset of disease, thereby increasing healthspan. However, likely owing to the use of an accelerated
ageing mouse model, no life extension was observed in this instance. However, a follow-up study by the same group
using naturally aged mice lead to delayed tumorigenesis and reduced age-related
decline leading to significant increase (up to 35%) in lifespan. Studies like these thus provide a convincing
rationale for developing therapeutic approaches for targeting senescent cells, so-called
“senotherapeutics”. These may include:
- Specifically inducing cell death in senescent cells (i.e. small-molecule compounds).
- Inhibiting the senescent secretome (i.e. inhibitors of inflammation).
- Preventing senescence induction (i.e. telomerase activators, geroprotectors).
- Boost immune response towards senescent cells (i.e. immunotherapy).
A few recent studies have published findings regarding the
elimination of senescent cells by small-molecule compounds. Wang et al (2016) identified the compound
ABT-263 as a potent inducer of cell death in senescent cells leading to
rejuvenation of aged tissue stem cells.
In another study, Yosef et al (2016) identified ABT-737 which through
the elimination of senescent cells from the epidermis of the skin of mice lead
to increased hair-follicle stem cell proliferation. Both ABT-263 and ABT-737 inhibit proteins
(BCL-2 family) known to play a role in cell survival.
Studies focused on the elimination of senescent cells are
only beginning to emerge and will no doubt gain momentum as they show
tremendous potential for improving health and wellbeing. One intriguing notion that may arise from
this research is concerned with the question of whether it may one day be
possible to treat many diseases with a single drug. If senescent cells play a role in the
development of many different diseases, then a drug that can eliminate
senescent cells in all cell types could act as both a preventative and a
treatment for many diseases.
One of the obstacles preventing research into
senotherapeutics from advancing and ultimately becoming translational to help increase
healthspan of individuals within the general public, is funding. However, this has not discouraged some
researchers who were determined enough to acquire funding through the help of
crowdfunding. The Major Mouse Testing
Programme (MMTP) raised over $50,000 towards research focused on eliminating
senescent cells and is still ongoing (Click Here).
A new start-up company, CellAge (click here) is also
interested in targeting senescent cells and has recently announced a
crowdfunding campaign (click here) to raise funds for their ongoing
research. CellAge aims are to “Increase human healthspan and reduce the
incidence of age-related diseases by helping the human body eliminate senescent
cells. Our breakthrough technology
concept harvests the promise of synthetic biology and recent findings in ageing
research to deliver novel products and therapies to enable people to live
healthier longer lives”
So if you are interested in stimulating research in this field for the benefit of all, then please make a donation (link here).
