A few weeks back I wrote a post about Aging, Lifespan, and Healthspan.

… at least I think I did. Or did I? Yes I did… (here it is)

I’m so forgetful these days.

How we can stay healthy as long as possible is a HUGE topic (War and Peace HUGE) and I merely skimmed the surface of this story of how and why we age.

How are you aging, would you say?

Every day there is more and more talk and research into aging as science-based technology thrusts us forward into a future with a promise of healthful longevity.

There are a number of reasons you or I might be interested in understanding aging, but for me, it’s all selfish.

I’m a one-note singer…. *Me me me me!

First of all, my parents died quite young by today’s longevity standards: Mom at 61, Dad at 73.

This would have been considered old, generations back… from the book Ageless: A 20-year-old today has better odds of having a living grandmother than a 20-year-old in the 1800s did of having a living mother.

Secondly, as an atheist who believes that an afterlife for me is a very remote possibility, I’d really like to make my life last a bit longer (no guarantees, I know) so that I can bug my family – esp. grandkids – and friends for longer, as well as see the monumental and exciting (and scary) changes coming to our world for as long as possible.

Yup, I like living.

Now, to understand the concept of aging is interesting, but truly, the bottom line is that I want to know how it can be slowed (or gasp, even reversed) so that I can have a longer lifespan than I might otherwise. Critical also is to have an increased HEALTHSPAN… the ability to live all my days in reasonably robust physical and mental health.

(OK, before I jump into this, here’s the fine print: I am not a scientific expert, but rather an interpreter. I have an interest in this stuff, so I’ll share with you what I’ve found and provide some links for you to follow if you have a deeper interest too. Also, science by its nature is incomplete and evolving, meaning that what I share today may be replaced tomorrow by newer research that sounds different. It’s science but it’s not omnipotent… )

… only I AM OMNIPOTENT (*oh Larry, get off your high horse…)

Today I thought I’d skim a level deeper by delving into just ONE of the Hallmarks of Aging.

Do you recall that I mentioned the 9 HALLMARKS OF AGING in my earlier post? NO? OK, here’s a quick summary:

  • 1. genomic instability
  • 2. telomere attrition
  • 3. epigenetic alterations
  • 4. loss of proteostasis
  • 5. deregulated nutrient sensing
  • 6. mitochondrial dysfunction
  • 7. cellular senescence
  • 8. stem cell exhaustion, and
  • 9. altered intercellular communication

This is enormously complex stuff but what the hell, let’s just leap off the cliff and dive into GENOMIC INSTABILITY as it relates to aging.

WHAT IS GENOMIC INSTABILITY?

At its simplest, it’s all about damaging our DNA (the stuff that makes up our genes) daily, monthly, yearly.

There are a lot of ways for DNA to become damaged. Just a few examples of these “gene damagers” are things like sun exposure, X-rays and CT scans, exposure to chemical toxins and carcinogens, tobacco use, and internal virus interactions with our genes.

We have lots of fix-it crews running around our bodies 24/7 replacing and repairing all the wear and tear in our genes and cells, but genomic instability is damage that the crew just can’t seem to get to for various reasons, like aging ie it’s not repaired.

David Sinclair, author of the book: Lifespan:Why We Age- and Why We Don’t Have To, states:

DNA damage accelerates epigenetic aging and the loss of information at the epigenetic level and the genetic level [causing genomic instability]. We know that breaking a chromosome is the best way to accelerate aging. We’ve done this in mice and it’s not pretty. Even just a few DNA breaks can accelerate aging. To avoid breaking DNA, try to avoid using microwaves, don’t have too many x-rays done unnecessarily, or CT scans; I think CT scans are essential, but don’t have CT scans done every year just because you’re curious what’s going on inside. That’s my view. Avoid radiation of the type that will break DNA.

The odd dysfunctional cell inside of us is not really a huge problem. But, as we get older, an increasing number of cells succumb to DNA damage and begin to accumulate.

Eventually, the number of these damaged cells reaches a point where they can compromise our organ and tissue function.

Normally, the body removes these problem cells via apoptosis (normal programmed cell death). Unfortunately, as we age some cells evade apoptosis. These rogue cells take up space in our tissue and send out harmful signals that damage the local tissue.

All these forms of DNA alterations may result in dysfunctional cells that, if not eliminated by apoptosis or senescence (loss of a cell’s power of division and growth), may jeopardize tissue and the body’s stable equilibrium. (Jones and Rando, 2011; Rossi et al., 2008)

Another possible outcome of damaged DNA is cells that mutate but do not destroy themselves. If a mutation damages the systems that regulate cell division, or disables the tumour suppression, cancer is the result.

The unchecked and rampant cell growth of cancer is probably the most well-known consequence of DNA damage.

Even chemotherapy agents designed to kill cancer can potentially damage DNA.

Finally, even if we craftily sidestep all the external threats to our DNA, the body still damages itself.

Oxidative stress produced by our metabolism can damage our DNA and mitochondrial DNA. Double strand breaks are often the result of this metabolic damage and can be lethal to the cell.

This is where the clean-up crews play their part. Humans have evolved a complex network of DNA repair mechanisms and enzymes that are collectively capable of dealing with most of the damage inflicted to nuclear DNA (Lord and Ashworth, 2012).

Unfortunately, this repair process is not perfect, and, sometimes, our DNA is not repaired. This can lead to the cell replication machinery misreading the information contained in the DNA, causing a mutation.

Many studies have demonstrated all of these genomic “damages” accompany aging.

Less DNA damage hopefully = less aging.

But here’s the big question for you and me:

What reasonable steps can we take to minimize this damage to our genes?

The simplest things are avoiding risks, such as: excessive sun exposure, industrial chemicals, too frequent X-rays, and smoking; also, stay away from radioactive waste, as there are no comic book superpowers from these mutations!

Beyond this, no drugs or therapies are definitively shown to prevent or repair DNA damage. The good news is human trials for DNA repair are well underway.

Example: there is a good deal of evidence to suggest that caloric restriction (CR) can help combat DNA damage, along with other beneficial effects.

From a 2007 American study (here): Over the last three decades, numerous laboratories have examined the effects of CR (Caloric Restriction) on the integrity of the genome and the ability of cells to repair DNA. The majority of studies performed indicate that the age-related increase in oxidative damage to DNA is significantly reduced by CR. Early studies suggest that CR reduces DNA damage by enhancing DNA repair.

Practically, cutting back our calorie consumption by about 30% through dieting or intermittent fasting is difficult, and for many, nearly impossible. as we know from all the failed diets out there.

A lot of research is ongoing into “magic pills” that have the ability to fool our bodies into thinking that CR is happening.

A 2020 Canadian study sums up much of this discussion. Compounds such as Resveratrol, Metformin (common diabetes medication), and Rapamycin show a lot of promise, but further human-based research is still needed.

(Disclosure (but not a recommendation): I take 600 mg of resveratrol daily. This is a personal choice for me based on my age and my family history. In concentrations below 1,000 mg, resveratrol exhibits anti-oxidant properties, but above 1,000 mg. may actually be a nasty pro-oxidant. It’s all about risk vs reward).

That was a lot to absorb. Are you still awake? Are you still alive?

Maybe… just maybe… you’ll cross the finish line after your Centenarian Olympics, eh?

In a future post, I’ll likely strike out into another of the Hallmarks of Aging.

Are your genes singing a song of longevity? Hopefully your inner genes are as tough as your blue jeans!