"Senolytics" is a new class of compounds that can
selectively killing off the aging cell, i.e., senescent cells. Senescent cells
are the cells that have stopped dividing.
They accumulate with age and accelerate the aging process by secreting
enzymes that causes inflammation and other age-related chronic problems. Therefore, in theory, if you could
selectively kill off these senescent cells without harming healthy cells, the “healthy
life span” of a living being should increase, meaning that killing off the
senescent cells should have the effect of slowing down the aging process.
This research on senolytics started about four years ago. On November 2011, a research team from the
Mayo Clinic led by Dr. Jan van Deursen published a study in Nature magazine showing that if you
could selectively destroy senescent cells, the mice had fewer age-related
diseases and lived up to 25% longer. The
study concludes that clearing senescent cells delays ageing-associated
disorders.1
On March 2015, a research team from the Scripps Research
Institute (TSRI), Mayo Clinic and other institutions led by Dr. James Kirkland,
Laura Niedernhofer, and Paul Robbins reported on the Journal Ageing Cells that senolytics compounds
could dramatically slow the aging process -- alleviating symptoms of frailty,
improving cardiac function and extending a healthy lifespan.2 The
researchers screened 46 different compounds to find ones that would interfere
with the ability of senescent cells to survive. The two that seemed to work best were
quercetin and dasatinib. The study results were very impressive: after a single
dose, mice had improved heart function that lasted up to 7 months. Periodic
doses worked too: mice showed improvements in a wide range of age-related
symptoms, including bone loss, tremors, grip strength, and overall body
condition.
Further testing in cell culture showed these compounds do
indeed selectively induce death of senescent cells. The two compounds had
different strong points. Dasatinib eliminated senescent human fat cell
progenitors, while quercetin was more effective against senescent human
endothelial cells and mouse bone marrow stem cells. A combination of the two
was most effective overall.
The two compounds they identified are, in some ways, polar
opposites. Quercetin is a common plant extract, found in a wide variety of
fruits and vegetables, especially capers, red onions, plums, and cranberries. Dasatinib, in contrast, is a highly
specialized cancer drug made by Bristol-Myers Squibb BMY -0.66% (NYSE:BMY) and
sold under the name Sprycel®. Dasatinib is used to treat CML, a form of
leukemia. Quercetin is cheap and easily available, while dasatinib is very expensive
and available only with a prescription.
The authors caution that more testing is needed before use
in humans. They note that both drugs in the study have possible side effects,
at least with long-term treatment.
Journal Reference:
1. Darren J.B. et al., “Clearance of p16Ink4a-positive
senescent cells delays ageing-associated disorders,” Nature 479, 232-236 (2011)
2. Yi Z. et al., “. The Achilles’ Heel of Senescent Cells:
From Transcriptome to Senolytic Drugs,” Aging
Cell 2015; DOI: 10.1111/acel.12344
Thanks for reading.
Connie
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