15th March 2015
New class of drugs could slow the aging process in multiple ways
A new class of drugs known as "senolytics" has been shown to increase the healthy lifespan of mice. Not only that, but multiple different aspects of the aging process can be improved simultaneously.
In multicellular organisms, including humans, cell division is essential for growth, development and repair. The average person will experience approximately 10,000 trillion cell divisions in their lifetime. As we age, our cells become less capable of dividing. Like a VHS tape being copied over and over again, the process of bodily growth and renewal is less and less accurate. The resulting errors contribute to disease and ultimately death.
Cells that have stopped dividing are known as "senescent" cells. Over time, they accumulate inside us and cause aging. They are similar to cancer cells – in that they can resist apoptosis (programmed cell death). Normally, between 50 and 70 billion cells die each day in an adult. This form of cell suicide helps to maintain a healthy equilibrium, or homoeostasis, ensuring an appropriate number of cells in the body is maintained. With senescent cells, however, this balance is disrupted. The build-up of senescent cells results in side effects, including the production of harmful chemicals. The situation can worsen dramatically if a cell's DNA has been seriously damaged – leading to out-of-control cell growth and cancer, or neurodegenerative disorders.
This week, a study was published in the journal Aging Cell, by researchers from The Scripps Research Institute (TSRI) and Mayo Clinic. They describe a new class of drugs known as "senolytics", which can selectively kill senescent cells – potentially restoring the balance of cell numbers. Two compounds were identified as candidates for testing, both found in existing medications. In Petri dish cultures, they produced the following results:
Individually, each compound was effective at removing the senescent cells in these locations, without damaging other cells. When combined together, however, the researchers observed even greater effects. Following the Petri dish experiments, a cocktail of both compounds was administered to mice in old age. The results were remarkable.
“In animal models, the compounds improved cardiovascular function and exercise endurance, reduced osteoporosis and frailty, and extended healthspan,” comments Laura Niedernhofer, PhD, in a press release from TSRI. “Remarkably, in some cases, these drugs did so with only a single course of treatment.”
FutureTimeline.net contacted the study authors to request more specific details. We received the following information regarding the mouse tests:
“We view this study as a big, first step toward developing treatments that can be given safely to patients to extend healthspan or to treat age-related diseases and disorders,” says Professor Paul Robbins, PhD, also from the Scripps Institute. “When senolytic agents, like the combination we identified, are used clinically, the results could be transformative.”
“The prototypes of these senolytic agents have more than proven their ability to alleviate multiple characteristics associated with aging,” said Mayo Clinic Professor James Kirkland, MD, PhD, senior author of the new study. “It may eventually become feasible to delay, prevent, alleviate or even reverse multiple chronic diseases and disabilities as a group – instead of just one at a time.”
"Senescence is involved in a number of diseases and pathologies, so there could be any number of applications for these and similar compounds," concludes Professor Robbins. "Also, we anticipate that treatment with senolytic drugs to clear damaged cells would be infrequent, reducing the chance of side effects."