Why We Age — The Junk In and Around Our Cells (listen up)

Famed anti-aging iconoclast, Dr. Aubrey deGrey tells us why we age and what is being done about it. Hear what he has to say and find out how the whole aging process can be filtered down to seven reasons.

REGULAR READERS know that I’ve been following the work of the uniquely brilliant biomedical gerontologist, Dr. Aubrey deGrey, the founder of the SENS Research Foundation, dedicated to understanding why we age, thereby freeing us from age-related diseases.

I wrote about Dr. deGrey twice before: In 7 Ways Science Will Repair the Damage of Old Age, I zig zagged between DeGrey’s approach to categorizing and intervening in the aging process to that of Dr. David Sinclair’s, which began this way:

How long would you want to live if you could stay as healthy as you were at 40?  Two prominent scientists are getting close to making this your reality as they work to repair the damage of old age.

And in Aubrey deGrey: “We Can Stop Aging”, I wrote that:

Aging begins before birth and happens as a side effect of metabolism, Aubrey claims.  Metabolism causes damage, but the damage is relatively minor for much of our lives until it accumulates sufficiently to manifest as some pathology (the scientific study of the nature of disease and its causes, processes, development, and consequences).

This distills down to:

Metabolism –> Damage –> Pathology

Now, as you’ll soon see, I’m still digging into Dr. deGrey’s research and findings about how to, at minimum, push out the age curve (the number of years we can live with health and vitality – “healthspan”), and, at maximum, live forever (which deGrey gets a lot of flack for, given his proclamation that it will eventually be possible)

.In large part, today’s material that I present for your edification comes from the SENS website and a long, smart interview about why we age that Dan Pardi, founder of Dan’s Plan, conducts with Dr. deGrey.

Those of who would like to immediately dispense with reading the rest of this article in favor of listening to the interview, simply click on the red arrow near Dan Pardi’s head:

Readers will get through the material quicker, so to you I say, read on…

You’re Not A Car, But…

Dr. deGrey often compares the human body to a vehicle.

Vintage cars can be more than 100 years old even though they were not designed to last that long. Nevertheless, they can stay intact and perform decades longer than intended because of the comprehensive maintenance, repair and parts replacement that their owners do.

In the case of the human body, the damage associated with aging is often self-inflicted as the consequence of its normal operation, and that damage accumulates and eventually exceeds what’s tolerable, and eventually it – the body – no longer works.

Generally speaking, the “damage” Dr. deGrey refers to concerns all aspects of the structure and composition of the body at the molecular or cellular level that progressively degrades throughout life as a side effect of the body’s normal metabolism. Once there’s too much degradation, it contributes to the various ills associated with old age, such as the loss of mental or physical performance.

The usefulness of the car analogy is to understand that there’s much we can do to maintain and repair our bodies over time, just like those auto hobbyist do with their vintage cars.

A Quick Look At Dr. deGrey’s Aging Categories

Before we get into the Dan Pardi’s interview of deGrey, I want to show you a few images from my article, 7 Ways Science Will Repair the Damage of Old Age, to make all this a bit more relevant to you.

Click pic

The seven categories cited below are the bedrock of the approach the SENS foundation takes to dealing with aging. Note that it lists the damage type and what type of intervention is needed:

• Replace;
• Reinforce;
• Remove; and
• Repair.

As you would expect, the intervention fits the situation.

To make this potentially relevant to you, consider the “damage type” behind two of the most fearsome diseases just ahead of us as we age, heart disease and Alzheimer’s.

According to the American Heart Association:

“Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially.” (source)

Well, I guess something’s gotta kill you eventually, but my worry is not death per se, but a very compromised life, like having some sort of heart disease dramatically diminishing one’s joie de vivre.

Which brings me to a study write-up called, Aging of the United States Population: Impact on Heart Failure, that puts the incidence of all CVD in the U.S. at 37% of the population in 2010, and estimates that it will grow to be 40.5% by 2030. (See this table.) These stats are probably similar across the industrialized world.

I bring this heart stuff up to underscore the value of categorizing the deterioration that is aging the way Dr. deGrey does it. As you’ll see as you read on, the interventions underway that address deGrey’s seven categories will potentially be useful not only to diseases like CVD and Alzheimer’s but also Parkinson’s, ALS/muscular atrophy, neurodegenerative diseases and a host of others Dr. deGrey touches on in the interview.

As you can see in the image below, four of Dr. deGrey’s seven categories contribute to heart disease; thereby, interventions to prevent or mitigate this damage will also diminish the incidence of CVD.

Among my circle of friends, Alzheimer’s a greater worry than CVD. This is not because these people eat right and are fitness buffs, and thus need not worry about heart disease. No, the reason people are more worried about getting Alzheimer’s than heart disease is because it attacks the essence of who we are – our minds.

There’s good cause for worrying about Alzheimer’s. According to the Alzheimer’s Foundation of America:

• 1 million Americans may have Alzheimer’s disease;
• Half a million Americans younger than age 65 have some form of dementia, including Alzheimer’s disease; and
• One to four family members act as caregivers for each individual with Alzheimer’s disease, which means – at minimum – one-quarter of families are affected by Alzheimer’s one way (you have it) or another (you care for someone who does).

It’s an understatement to say that Alzheimer’s is a problem, which is why it’s important to understand how this disease happens and what are the likely interventions.

Although Dr. deGrey has classified the damage coincident with aging into seven major categories, this does not reflect his view that there are only seven mechanisms or processes that account for why we age, but rather that his particular bundle of seven lend themselves to specific interventions.

For each of deGrey’s categories there is a corresponding generic intervention and approach that may differ in detail from one example within the category to another, but only in detail; the basic thing is the same, he says.

For more on this, be sure to click on the “SENS solution” link under each of the following seven categories of aging.  Now, let’s dig into Dr. deGrey’s work and insights about why we age.

1. Cells Die and Aren’t Replaced — Cell Loss and Atrophy

The Replacing lost cells section of the SENS website describes cell loss and atrophy:

Every day, our cells are damaged by both tiny molecular-level insults and by obvious trauma. Some of these damaged cells are repaired, but others are either destroyed, or forced into a dysfunctional ‘senescent’ state where they can no longer divide, or commit ‘cellular suicide’ (apoptosis) for the greater good of the body.

The pools of specialized, tissue-specific stem cells replace some of the lost cells, but the degenerative aging process makes these stem cell pools less effective at repair over time.

The net result is that over the course of many decades, long-lived tissues like your brain, heart, and skeletal muscles begin to progressively lose cells, and their function becomes increasingly compromised. Muscles weaken, and don’t respond properly to exercise or injury. The brain loses neurons, contributing to cognitive decline and dementia, as well as to loss of control over fine muscle movements (a process that ends in Parkinson’s disease). The thymus – the gland in your breastbone where a major class of immune cells mature – shrinks, leaving you more vulnerable to infectious disease as fewer fresh immune cells are produced.

(Click here to read the SENS solution to cell loss and atrophy.)

With that preamble, here’s Dr. deGrey:

2. Too Many Cells — Cancerous Cells

The Making cancerous mutations harmless section of the SENS website describes cancerous cells:

Two types of damage accumulate in our genes as we age: mutations and epimutations. Mutations are damage to the DNA sequence itself, whereas epimutations are damage to the “scaffolding” of that DNA, which controls how and when genes get turned on in the cell.

For practical purposes, both mutations and epimutations ultimately harm us in the same way: by causing abnormal gene expression, whether it’s by increasing or decreasing the amount of a protein encoded by a gene being produced, by altering in the conditions under which that production is activated, or by altering the structure and function of the ensuing protein itself. Because of their similar effects, an approach that prevents the negative consequences of these changes in gene expression can be used to make both kinds of damage harmless, despite the fact that the molecular basis of mutations and epimutations are quite different.

So what kind of harm can the changes in gene expression resulting from (epi)mutations cause?

The one that most people know about is cancer, which is the result of a series of (epi)mutations that happen in sequence in the cell, leading to its uncontrolled growth.

Other kinds of (epi)mutations also occur in our cells over time, and some scientists have worried that these non-cancer-causing (epi)mutations might also contribute in different ways to age-related disease and disability. But there is good reason to believe that there aren’t enough such mutations to actually have a meaningful impact on our health.

This is because the threat of cancer from even a single (epi)mutation is so great that it forces the body to develop defenses against (epi)mutations that far exceed what would be needed to prevent a meaningful burden of non-cancer (epi)mutations  from occurring.

(Click here to read the SENS solution to cancerous cells.)

Dr. deGrey:

Cancer immunotherapy has caught on. Right now, a dear friend of my sister’s who has brain and lung cancer is about to be entered into a trail that uses this therapy.

Cancer immunotherapy is a type of cancer treatment designed to boost the body’s natural defenses (immune system) to fight the cancer. It uses substances either made by the body or in a laboratory to improve or restore immune system function. The trick that scientists are trying to figure out is how to tip the balance between the ingenuity of the cancer and the ingenuity of the immune system.

3. More too many cells – Death-Resistant Cells

The Removing dysfunctional cells section of the SENS website describes death-resistant cells:

Our cells have built-in programming that sometimes veers them far away from their normal fate. Some of this programming watches out for conditions emerging within the cell that could put the rest of the body at risk; similar systems exist because the body no longer has need for the function that the cell normally fulfills.

Pushing these cells to undergo such transformations is favored by evolution because it meets short-term needs, and having a few of these abnormal cells in the body for is nearly harmless. But the number of these cells in our tissues gradually rises over time, until by our fifth decade or so they begin to reach levels that are harmful to normal tissue function.

Examples that are reviewed here include:

• Classic senescent cells;
• Cells in fat tissue; and
• Immune cells.

(Click here to read the SENS solution to death-resistant cells.)

Dr. deGrey:

Dr. deGrey puts too many cells, or “Death-Resistant Cells”, into a separate category due to the distinction between having too many cells that are dividing when they shouldn’t versus having too many cells hanging around because they refuse to die when they should.

This distinction informs the intervention to solve the problem. In this case, Dr. deGrey says that too many cells refusing to die when they should are theoretically easy to get rid of than those that are dividing,

The likely approach, he says, is called “Suicide Gene Therapy”, already a routine procedure in laboratories, but not yet a clinical therapy to eliminate these over abundant cells that don’t want to die when they should.

4. Replacing Lost Cells — Mitochondrial Mutations

Whereas the first three categories covered above are about the number of cells we have, this one deals with what happens within cells.

The Preventing damage from mitochondrial mutations section of the SENS website describes mitochondrial mutations:

Mitochondria are the living machines within cells that act as their “power plants,” converting the energy-rich nutrients in our food into ATP, the form of energy that directly powers biochemical reactions in the cell. Unlike any other part of the cell, mitochondria have their own DNA (mtDNA), separate from the DNA in the cell’s nucleus, where all the rest of our genes are kept.

Just like real power plants, mitochondria generate toxic waste products in the process of “burning” food energy as fuel – in this case, spewing out highly reactive molecules called free radicals, which can damage cellular structures. And the mtDNA is especially vulnerable to these free radicals, because it is located so close to the center of its production.

At worst, a free radical “hit” to the mtDNA can cause major deletions in its genetic code, eliminating the mitochondria’s ability to use the instructions to make proteins that are critical components of their energy-generating system.

Lacking the components needed to produce cellular energy the normal way, these mutant mitochondria enter into an abnormal metabolic state to keep going — a state that produces little energy, while generating large amounts of waste that the cell is not equipped to metabolize.

Perversely, the cell tends to hang onto these defective, mutant mitochondria, while sending normal ones to the recycling center, so if just one mitochondrion suffers a deletion; its progeny quickly take over the entire cell.

Although this happens to just a few cells in our body, those few cells wind up doing disproportionate damage to the body as a whole, because they dump the waste that their mutant mitochondria generate into the circulation, poisoning their environment by causing oxidative stress to rise all over the body.

(Click here to read the SENS solution to Mitochondrial Mutations.)

Dr. deGrey:

5. Damage Inside the Cells — Intracellular Junk

We continue with issues within cells.

The Clearing waste accumulation out of cells section of the SENS website describes intracellular junk:

The proteins and other constituents of our cells are all eventually damaged as the result of biochemical accidents that occur during normal metabolism, or simply outlive their usefulness.

Cells have a variety of systems for breaking down and recycling such unwanted materials, allowing them to clear garbage out of the way and reuse the raw materials. One such system is the lysosome, a kind of cellular “incinerator” that contains the most powerful enzymes in the cell for breaking mangled molecules down into manageable pieces. However, sometimes these constituents are so badly fused together that not even the lysosome is able to tear them apart. And if something can’t be broken down in the lysosome, there’s nowhere else for it to go: it just stays there until either the lysosome disastrously ruptures, or the cell itself is destroyed.

Over time, the material that the lysosome has been unable to break down accumulates inside of it, and eventually the rising buildup of such material begins to interfere with the lysosome’s function. This is an especially big problem for cells that have to last for a lifetime in our bodies, such as the cells that make up heart, the back of the eye, and nerve cells in the brain and elsewhere.  And of course, when the cell’s ultimate garbage disposal system starts malfunctioning, it impairs the function of the cell as a whole. And as more and more cells become dysfunctional over time, tissue function is impaired, and age-related disease sets in.

Consider what happens to macrophages, for example – the cells from the immune system that are responsible for protecting our blood vessels from being damaged by infiltrations of toxic byproducts of cholesterol. “Macrophage” means “big eater,” and these cells protect our arteries by surrounding and swallowing these toxic materials and then sending them to the lysosome, where they are thoroughly digested and their useful raw materials are released. But as macrophages consume more and more of these toxic materials, their lysosomes become engorged with byproducts they can’t break down. Eventually, they cease functioning, and either become immobilized and dysfunctional in the artery wall, or die outright.

This buildup of sick and dying macrophages in the artery wall is the basis of atherosclerosis, the plaques in our arteries that are responsible for heart disease. As their numbers gradually increase over time, the injury swells and festers until it eventually bursts, spewing out clots and other materials that trigger heart attacks and strokes.

Similarly, the inability of particular cells to break down their specific cellular waste products is also a key factor driving several types of neurodegenerative diseases (such as Alzheimer’s and Parkinson’s), as well as macular degeneration, which is the main cause of blindness in people over the age of 65. So, it’s very important that we find a way to clean the decades of stubborn waste buildup out these long-lived cells.

(Click here to read the SENS solution to Intracellular Junk.)

Dr. deGrey:

6. Damage Outside the Cells — Extracellular Junk

The Removing junk from between the cells section of the SENS website describes extracellular junk:

Extracellular junk is accumulations of sticky, malformed proteins that no longer serve their function, but instead impair cell or tissue function by their presence.

Extracellular junk is different from extracellular cross-linking, which is a form of damage that occurs between structural proteins and impairs their ability to move. Most extracellular junk is termed “amyloid” of one variety or another.

The most well-known form of extracellular junk is beta-amyloid: the stifling, web-like material that forms plaques in the brains of patients with Alzheimer’s disease, and also (more slowly) in everyone else’s, and impairs cognitive function.

There are also a variety of similar aggregates that form in other tissues during aging and contribute to age-related diseases, including islet amyloid in Type II diabetes and senile cardiac amyloidosis, which is a major contributor to heart failure. In fact, there is some evidence that senile cardiac amyloidosis may be the main cause of death in people who survive beyond age 110.

(Click here to read the SENS solution to Extracellular Junk.)

Dr. deGrey:

More about senescence and autophagy read my articles:

• How Intermittent Fasting Ignites Cellular Autophagy and A Longer, Healthier Life
• 11 Ways To Increase Your Lifespan

7. Outside the cell — Extracellular Crosslinks

The Breaking the extracellular crosslinks section of the SENS website describes extracellular junk:

Many of the major structural features of the body are built out of proteins that are laid down early in our life, and then more or less have to last for a lifetime. They are never recycled or replaced, or are only recycled over the course of many decades slowly.

The healthy functioning of these tissues relies on these constituent proteins maintaining their proper structure. Such proteins are responsible for the elasticity of the artery wall, the transparency of the lens of the eye, and the high tensile strength of the ligaments, for example. But occasionally, blood sugar (and other molecules in the fluids in which these tissues are bathed) will react with these proteins, creating chemical bonds called crosslinks.

Crosslinks act like molecular “handcuffs,” taking two neighboring proteins that were previously able to move independently of one another and binding them together, impairing their function in the same way that occurs to participants in a three-legged race.

In the case of the artery wall, for instance, the crosslinking of strands of the protein collagen prevents them from spreading apart from one another to accommodate the surge of the pulse being driven forward by the pumping action of the heart. As more and more strands of collagen become crosslinked together over time, the blood vessels to become ever more rigid, leading to a gradual rise in systolic blood pressure with age.

With the loss of the cushioning effect provided by free-moving collagen in the blood vessels, the force of the surge of blood that is driven into the arteries by the pumping action of the heart is carried directly to organs like the kidneys and the brain, damaging to the structures that filter our blood and that connect the functional regions of our brain, and putting us at risk of a stroke.

(Click here to read the SENS solution to Extracellular Crosslinks.)

Dr. deGrey:

Well, dear reader, now you have a good deal of insights about why we age and what scientists are doing about it to find interventions that replace, reinforce, remove or repair, as each situation requires.

In the meantime, there’s much you can do to slow down the aging process and maintain (or regain) your vitality. I encourage you to check out the CATEGORIES (scroll up, look right) and dive into your topics of interest.

Find the one thing you’re willing to do, and begin it now.

Last Updated on July 7, 2023 by Joe Garma