Fighting Aging: A Paradigm Shift in How We Approach Health

Fighting Aging: A Paradigm Shift in How We Approach Health
Growing old is inevitable but rejuvenating cells and tissues may help to avoid the negative effects of aging and disease.

Aging is a natural part of the life cycle that happens universally across most living organisms. It's an inevitable part of the process of life and death.

Although aging is inevitable, lifestyle behaviors can immensely impact it. Everybody knows the basic rules for a healthy life, including eating healthy, maintaining a healthy weight, exercising regularly, getting enough sleep, and having a rich social life. As cliche as they may seem, it turns out that these behaviors can add a staggering 10 years or more to your life.

So now that we know that healthy behaviors can have a huge impact, is that where it ends? Do we have to go the long haul of incorporating all these into our lifestyles or can science help quicken the process? These questions sum up the direction in which science is heading next. Up until now, diseases such as heart disease, cancer, diabetes, and dementia, were combated individually. Billions of dollars were spent on discovering treatments to try to eradicate these scourges. We know that many of these conditions are age-related. So what if we have been approaching longevity the wrong way? Instead of focusing on disease, shouldn't we take aim at aging itself? Perhaps rejuvenating cells and tissues can help to avoid the negative effects of aging and disease in the first place. But before we dive into all that, let’s see what aging is and why we age.

What is aging?

In a 2013 landmark paper, aging is characterized as the progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. Indeed, it is often described as the biggest risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. At the cellular level, aging includes changes in the genome, telomeres (the protective caps at the ends of chromosomes), epigenetics, protein management, mitochondrial function (the energy plant of cells), and more.

Why do we age?

Why we age is still poorly understood. However, leading theories range from simple damage accumulation to natural selection not selecting traits for longevity as lacking any biological advantage where genes beneficial for growth early in life turn negative later in life, to a now mostly-rejected finely tuned programmed aging.

Aging research is emerging

Aging research has been advancing rapidly in the last few decades. Many of our insights came from studying centenarians with longevity genes or studying the differences in lifespan in mammals from the short-lived mice (2 yrs), to humans, to the impressive long-lived Bowhead whale (200 yrs).

The field really got kick-started with research done by Cynthia Kenyon, a professor at UCSF, who discovered that mutations in a few genes doubled the lifespan of  C. elegans, a model organism in biology. Since then several breakthroughs have led to the discovery of over a hundred interventions that can extend the lifespan of a mouse including specific diets, and medications such as metformin, rapamycin, and Acarbose. The National Institute on Aging (NIA) even has a program to research lifespan extension in mice systematically. Thus far, only a few are making it into the clinic, with the TAME trial, the largest human trial testing diabetes medication, metformin, for aging, slated to begin sometime in the near future. A bit further along is research being done with companion pets. You can read about that in our blog post here.

Cellular reprogramming to rejuvenate humans

More recently a novel, exciting approach is starting to appear. This approach attempts to genetically reprogram cells to a younger state or as it is called rejuvenate cells. This is based on the work done in 2006 by Nobel laureate Shinya Yamanaka for the discovery that mature cells such as skin cells can be converted back to stem cells by adding a mix of transcription factors (proteins that regulate gene expression). A decade later, in 2016, researchers discovered that the same mix of transcription factors improved markers of aging laureate Shinya Yamanaka in mice through genetic reprogramming at the cellular level. It was demonstrated that the reprogramming was having its effect through remodeling the epigenome of the cells. This reprogramming of cells to rejuvenate and reset biological clocks sparked the launch of several biotech companies to develop therapies for rejuvenating humans. It is yet to be seen if this new crop of biotech companies, mostly based on research in petri dishes, can get to actual therapies and clinical applications.

Measuring aging

To measure is to know, stated Lord Kelvin. This is easier said than done when trying to measure aging. Most straightforward is your chronological age as it is simply the time that has passed since your day of birth. Chronological age however doesn't tell you how old you are biologically nor can it be impacted by therapeutic interventions so it's not exactly the best measuring stick.

Your biological age can be impacted by lifestyle and possibly other interventions, as discussed earlier. A person who is 60 years old may actually be biologically much older because of eating or smoking habits.

There are a few ways to assess your biological age, including fitness, blood markers, and imaging, but these are too crude. For many decades, biological researchers have tried finding a precise clock for aging. In the early 1960s, it was discovered that cells are not immortal but die after 40 to 60 rounds of replications, with the number of replications as an approximate measure of age. In the 80s, the length of telomeres (protective caps at ends of chromosomes) were proposed but that didn't pan out. And then, about a decade ago, a strong correlation was found between epigenetic markers and age by Steve Horvath.

Epigenetics comes from the Greek prefix epi (meaning "over, outside of, around") and roughly implies features that are on top of your DNA. Epigenetics determine how genes are expressed without changing the underlying genetic code. You can compare it a bit with an orchestra, your DNA represents the musicians and the configuration of seating, and your epigenome will be the conductor, guiding the orchestra in creating the music.

Turns out that the epigenome changes with age and this is what the epigenetic clocks are measuring. Several versions from this type of clock have since been launched. Each with its strengths and weaknesses, You can read more about epigenetic clocks and a story of a reporter who tried it out.

What's next

The longevity field has come a long way and is moving from fringe science into the mainstream.

Its goals are shifting from "immortality" to extending healthspan.

Along with the maturation of the field are its goals which are shifting from "living forever", with its own set of ethical implications, to a focus on extending healthspan as a goal. Where academia and biotech companies are pursuing a longer and healthier human lifespan. Something that we'd all want for ourselves, family, and friends.

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