Scientists are making great strides towards understanding how they can slow and even reverse some of the primary drivers of aging, including caloric restriction, stem cells, DNA damage and inflammation.
Sinclair’s lab has successfully rejuvenated aged mice by altering their epigenetics, offering hope of developing an age-reversal pill.
What is aging?
With recent successes of genetically engineered medicines in reversing cancer or heart disease, it seems natural to wonder whether we could turn back the clock on other common afflictions like aging. Studies on primary drivers of aging are already flourishing – scientists are investigating ways of reversing stem cell dysfunction, proteostatic dysfunction, telomere erosion, DNA damage, mitochondrial dysfunction and inflammation as possible interventions against premature aging.
Studies conducted over the last several years have challenged the traditional view of aging as a process characterized by gradual accumulation of cell damage that ultimately results in functional decline throughout late adulthood. Now, researchers believe some physiological deterioration – including diseases related to aging – occurs because certain kinds of cells become nonfunctional over time.
These insights have created a revolution in how scientists view aging and life extension. This paradigm has major ramifications for medical science, public policy and social values.
Accordingly, there has been renewed interest in drugs that can reverse or even slow aging by blocking certain cellular signals. Such drugs are called rapamycin analogs and work by inhibiting large molecular pathways involved in aging processes. Another promising direction in research on anti-aging involves mimicking caloric restriction’s anti-ageing benefits which have been demonstrated to extend mouse lifespans.
Cellular reprogramming offers another intriguing hope of reverse aging; this process uses fully developed cells with four factors to reprogram them as embryonic stem cells – potentially helping regenerate tissues and organs, and potentially turning back time on our entire organisms.
One laboratory working toward this possibility recently made headlines with their groundbreaking discovery: they managed to rejuvenate eye nerves of older mice, making them look and act younger as a result. This breakthrough could pave the way for effective age-related disease treatments as well as total body rejuvenation becoming possible in future.
How does aging happen?
Researchers still don’t fully understand what causes aging, but one theory holds that damage caused by daily activities (chemicals, radiation or sunlight, for example) slowly accumulates over time to make cells less functional. Another theory holds that genes govern natural aging processes but lifestyle habits (diet, exercise and smoking habits for instance) can speed up or slow down this process.
Researchers have also observed that different organs age at differing rates. For instance, heart tissue may deteriorate more quickly than other tissues of the body, as determined by measuring proteins released as we age and measuring our “biological age,” which represents approximately how much molecular damage will eventually result in disease or disability.
As one ages, their cells become damaged or wear out and die, forcing the remaining ones to work harder than before, leading to an accumulation of damaged or worn-out cells that eventually stop functioning properly and lead to diseases like cancer, cardiovascular disease and Alzheimer’s.
Scientists have often argued that old cells must simply be destroyed to make room for new ones – a process called programmed cell death (apoptosis). Others, however, have noted that many older animals or people don’t appear riddled with mutations and that mutated cells don’t seem related to age at all.
Sinclair and her team recently developed a technology called ICE that allows them to reprogram mature cells back into stem cells that can grow and develop into any tissue type in the body. They refer to it as inducible changes to epigenome, and have already used this process on skin cells from mice that look and act two years younger than their siblings; researchers are currently working on reprogramming neurons back to an embryonic state using this same process.
This technology may prove invaluable in developing drugs to treat age-related diseases and may help scientists discover ways to slow or reverse aging. Indeed, one researcher from Cold Spring Harbor Laboratory is working closely with Sinclair’s team in an experiment designed to see whether such an approach can actually extend mouse lifespan.
How can we reverse aging?
Scientists around the globe are actively engaged in efforts to slow, halt or reverse aging. This could one day yield medicines to reduce risks related to age-related illnesses while helping avoid many of the inconveniences of growing old.
But increasing life expectancy has long been met with suspicion due to fears it might lead to increased illness and disability costs and ultimately raise health care costs. What would be much more effective, according to experts, would be taking measures directly against causes of aging such as genetic mutation.
New research indicates that human cells may be capable of doing just that. Researchers from California’s Salk Institute found that increasing levels of an age-decaying protein could prevent cell mutations and age-related illnesses such as Alzheimer’s.
Researchers explain that the key to understanding human aging lies in how cells’ information is encoded genetically. Our genome remains relatively stable while epigenome changes with our environment and lifestyle choices over time, and when its original instructions for functioning become disjointed or lost altogether, accelerated aging occurs as cells lose function or degenerate uncontrollably – leading to cancer, cardiovascular disease and dementia among other aging-related diseases.
One area of research that is particularly exciting is cellular reprogramming. This process involves taking fully developed adult cells and returning them to more primitive states; 2012 Nobel Prize winner Shinya Yamanaka demonstrated this using four transcription factors that reprogrammed adult mice cells into induced pluripotent stem cells (iPSCs) without altering their identities as mature mice cells.
Scientists are taking various approaches towards this end, such as mimicking the anti-aging effects of caloric restriction and undoing cell damage caused by oxidation. Furthermore, several medications currently in use such as rapamycin – an inhibitor of the TOR pathway – have demonstrated anti-ageing benefits; ultimately they hope to use the reprogramming approach to achieve whole body rejuvenation in humans.
What are the risks of reversing aging?
Researchers who wish to create the fountain of youth must first understand why we age in the first place. One answer may lie within epigenetics – which studies how changes to gene activity influence cells without changing DNA sequence. Studies conducted on simple organisms and humans alike have demonstrated how altering how certain genes are turned on or off can slow or even reverse aging processes.
Scientists once believed that mutations were the sole source of aging; however, recent discoveries suggest otherwise. Epigenetic modifications–changes to how genes are expressed–may play a major role. Although epigenetic modifications do not alter genetic code directly, they still affect how the genes act upon one another.
Scientists have also observed that people age at differing rates, with some developing disease and showing the effects of aging much earlier than others. This may be attributed to toxic biological byproducts accumulated over time such as oxidative stress, inflammation and cell degradation that cause harm over time. Also contributing can be cells’ metabolism which releases waste products harmful for body.
Scientists are researching numerous techniques to halt or reverse the aging process, such as caloric restriction, taking anti-ageing medications and using cellular reprogramming – turning fully developed cells into stem cells to regenerate or replace damaged tissues and organs.
The latter approach has proven particularly successful. Researchers in Sinclair’s lab at Harvard Medical School have discovered a way to reverse mouse aging through embryonic stem cell (ESC) conversion; ESCs can not only differentiate into various cell types but can also grow and repair tissue within the animal itself.
Researchers have successfully reprogrammed cells into more similar ESCs by injecting them with four compounds called Yamanaka factors. Sinclair’s team successfully used this combination in mice lab settings to slow their aging and restore vision in older animals; now working towards scaling this research to human skin cells which may ultimately result in whole-body rejuvenation.
