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Is All This Talk About Aging Getting OLD?

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As Peter Attia, Canadian-born physician whose medical practice focuses on the science of longevity, asks in his lectures:

What is the greatest risk factor for atherosclerosis (deposition of plaques of fatty materials on arteries inner walls?“) …

… the answers from students and laypersons alike rebound back at him in rapid fire: smoking!… high blood pressure!… apoB!… LDL!… inflammation!…

These are all good logical answers.

And then he responds, “… the number one cause of atherosclerosis is age, hands down.

Yup, aging kills.

Welcome to Part 3 (Parts 1 and 2 are here and here) of my occasional dive into the science and maybe… science-fiction-like discussion of AGING, LIFESPAN, and HEALTHSPAN.

Yes, aging, and what we can do to slow it down. Or heaven forbid and glory be… reverse it!

We’re in the opening innings of a long game versus the profound effects of aging that could go well past the 9th inning before we declare something resembling a winner.

But this doesn’t mean we shouldn’t take a few swings of the bat when some tempting pitches come floating across our plate that auger well for a single or a double, ie. a potentially longer lifespan and healthspan.

So, this week, I’m cherry-picking another one of the 9 Hallmarks of Aging that I find particularly interesting.

Please remember, this is written in very simplistic terms. This topic is a very deep hole with exhausting complexity.

But first, as always… the fine print.

(I spent my professional life working in the sciences, but I am not a scientific expert. I am an interpreter with 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… )

Part 3, let’s go…

Senescence… my name is Cellular Senescence

It’s like we live in the world of The Walking Dead except internally, in our guts and cells, we have The Floating Dead… yes, Zombie cells…

Cellular senescence … way back in 1961, a couple of researchers by the names of Hayflick and Moorhead tried an experiment (here) to see if human cells could multiply over and over indefinitely in a lab dish.

The answer? Nope, these cultured human cells do not replicate forever but start to slow their divisions and just kind of nod off into a Zombie Zone. This is called cell senescence (the term senescence comes from the Latin “Senex”, which means “old man” in Latin).

But these cells don’t actually die.

In fact, they have an increased resistance to cell death by finding pathways that allow them to escape our immune system clearance and survive. They also begin to do some weird things, like changing their shape and size as well as secreting inflammatory molecules, which, in turn, can cause other cells to become senescent.

Scientists suggest that one of the main reasons that our cells have gained the ability to cause cells to stop dividing and doing their “job” is that senescence prevents the replication of cells that contain damaged DNA. This serves a critical function in preventing cancer and limits tissue damage by stopping the multiplication of faulty cells.

The link between aging and senescence has been well established. Simply, as we get older, our cells continue to be exposed to a cumulative stress (of many internal and external forms), which, ultimately, leads to an increase in the number of cells that become senescent.

On the bright side, Cellular senescence may play an important role in tumour suppression, wound healing, and protection against tissue fibrosis…

… but, there’s increasing evidence that the accumulation of senescent cells as we age may produce harmful effects and can contribute to tissue changes, biological aging, and many age-related diseases.

Senescent cells secrete hundreds of factors that include pro-inflammatory cytokines, chemokines, growth factors, and proteases (Kuilman and Peeper, 2009), some helpful, while others are nasty.

So, do senescent cells actually cause us problems as we grow older? It would seem, yes, according to this summary in December 2020 from the journal, Aging Cell.

Senescence is likely a double-edged sword.

Can we do something about this to increase our lifespan and healthspan? Anything?

There is really only a little we can actively do right now… but… we also have a lot to look forward to as research lifts the cover off some of these aging mysteries.

Strategies against cell senescence that can be used as “therapy” in humans can be classified into the following 3 groups:

  • non-drug interventions that prevent the accumulation of senescent cells, such as avoiding excessive UV radiation, and healthy dietary habits that include foods with anti-oxidation activity. Also, calorie restriction would appear to be beneficial as restricting calories is known to suppress oxidative stress (here), a major cause of DNA damage and cancers.
  • pharmacological therapies aimed at reducing the amount of inflammatory molecules secreted by already existing senescent cells.
  • pharmacological therapies aimed at reducing the number of senescent cells (or what researchers call senolytics). In early studies, senolytics appear to delay, prevent or alleviate frailty, cancers and cardiovascular, neuropsychiatric, liver, kidney, musculoskeletal, lung, eye, haematological, metabolic and skin disorders, as well as complications of organ transplantation, radiation and cancer treatment (Journal of Internal Medicine, 2020.)

LAST WORD: If you intend to participate in the Centenarian Olympics, your and my chances should be significantly increased if the quandaries of cellular senescence can be better understood and alleviated.

While you’re waiting for this to happen, maybe try working on your handstands!

Jagmeet Singh (Canadian NDP Party Leader) can walk on his hands at 42… will he still be able to do this at 100??

Are You In The Prime of Your Genes?

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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!

You Have The Right to Live, But Do You Have The Fight to Live?

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Take a deep breath… smile… there, that’s a good beginning… Namaste…

I’m aware that most of my blog followers and readers are of an age demographic that resembles me… near or at Senior’dom.

This post will be skewed towards your world, ie. the elder demographic’s area of interest, but I also want to stress to you younger “kids” that now is the real time to pay attention to the stuff I’m talking about here today.

You might think this post is a bit nerdy, yeah yeah, but hang tough, because it’s worth it for you, and those you love.

Today it’s all about Aging, Longevity, and perhaps most importantly, Healthspan.

In the past year or so, I’ve developed a greater and greater interest in the process of aging and the science of how it happens, and what can be done to delay aging, and yes, ultimately, death.

Aging is very complex stuff because our biological humanity is enormously complex, filled with millions of internal actions and interactions. We know so much, but in reality, we know so little.

Both of my parents died at relatively young ages – unnecessarily young in my opinion – from heart conditions that were, at a minimum, partly a result of lifestyle choices they made.

… the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution.” Journal – CELL

Yes, for my parents, genetics played a part in their too short lives as well, but I should learn from their choices and CHOOSE to make better decisions, based on what science tells us today.

I was cosmically lucky to be born, and I should choose to honour that luck and life with grace and effort.

Critically, achieving a greater age and lifespan is almost meaningless without a longer healthspan, life without major physical or mental infirmities.

This is what we all want for ourselves and our family, and unfortunately so often fail to achieve.

First off, as I talk about these topics, I’ll acknowledge that I’m not an expert.

BUT. I think the topic is important enough to us all to at least attempt a greater understanding.

I’ve often discussed “good science” (peer-reviewed, reproducible, double-blind where applicable) in my posts, and I’ll be paying close attention to this as I go along, while also bearing in mind that scientific knowledge, like technology, is CONSTANTLY EVOLVING.

What’s the bottom line here?

A longer, healthier life.

The end result of my curiosity is to tap into the truly limited knowledge that we possess on aging, lifespan and healthspan, and extract some useful guidance to increase my chances of breathing, in a healthy state, just a bit longer than I might have otherwise.

I’m merely scratching the surface on this today, so expect to see more posts that address this important topic as weeks and months go along.

Sound good to you? No?? Let’s jump in anyway! …

Much of the research and discussion that I draw from is originating from the bright minds of three scientists (although there are so many more out there whose work is equally valid and important).

The first is David Sinclair, PhD, an Australian biologist, Professor of Genetics and co-Director of the Paul F. Glenn Center for Biology of Aging Research at Harvard Medical School. He is known for his research on aging with a focus on epigenetics. He is the author of a 2019 book titled, Lifespan: Why We Age – and Why We Don’t Have To. The book has some complexity, but he does a pretty fair job of making it understandable to the lay person.

Second up is Dr. Jennifer Doudna, PhD, an American biochemist who has done pioneering work in CRISPR gene-editing. Dr. Doudna received the 2020 Nobel Prize in Chemistry, with Emmanuelle Charpentier “for the development of a method for genome editing.” She is a professor in the Department of Chemistry and the Department of Molecular and Cell Biology at the University of California, Berkeley. Her discoveries are hugely exciting for a number of reasons related to aging and other diseases which I’ll get to eventually, today or in the future.

Finally, Dr. Peter Attia is a Canadian-born physician whose medical practice focuses on the science of longevity. Attia received his M.D. at Stanford University, then spent five years at the Johns Hopkins Hospital in Baltimore as a general surgery resident followed by two years at the National Cancer Institute (NCI) at National Institutes of Health as a Surgical Oncology Fellow. In 2014, Attia founded Attia Medical, PC, a medical practice focusing on the applied science of longevity and optimal performance. His in-depth and well-communicated podcasts on aging and longevity can be found here.

OK… AGING…

Eight years ago, a landmark article was published in the science journal CELL that outlined the 9 hallmarks of aging…

These hallmarks are:

  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
  9. altered intercellular communication.

Each of these hallmarks was intended to meet the following criteria:

  1. it occurs during normal aging
  2. increasing it experimentally speeds up aging
  3. slowing it experimentally changes the normal aging process and increases healthy lifespan.

Every one of these 9 hallmarks is a long story unto itself. I give you these points so that you can do your own investigations should you choose.

There are a plethora of investigators (3 of whom I mention above) that are burning midnight oil to uncover interventions to alleviate the changes that occur with aging – some are practical and relatively simple, others are looking at medical and pharmacologic approaches that show promise.

Yada yada yada… your job and mine… is to attenuate, not stop totally, each of these aging processes and reach out to eventually participate in the Centenarian Olympics, a term used by Peter Attia to describe reaching the age of 100 with the ability to be mobile and mentally competent.

Here is how Attia describes the functional requirements of participation in the Centenarian Olympics: When you’re 100, you should be able to: 

  • Get up off the floor under your own support
  • Pick up a child that’s running at you (or, similarly, do a 30-pound goblet squat)
  • Walk up and down 3 flights of stairs with 10 lbs. of groceries in each hand
  • Pull yourself out of a pool
  • Lift a 30 lb. suitcase over your head (i.e., when you’re putting your luggage in an overhead bin on an airplane)

These requirements can be difficult for a 75 year-old in reasonable health. It will take consistent and determined effort to do it at 100!

One of the best and most effective ways that science shows we can take control over almost all of the hallmarks of aging come in one recipe ingredient: exercise. This is a great starting point on the journey to successful aging.

From a 2018 article in the Frontiers of Endocrinology, the authors write: “… regular physical activity in the older population—especially aerobic and resistance training—plays an important role at a multisystem level, preventing severe muscle atrophy, maintaining cardiorespiratory fitness and cognitive function, boosting metabolic activity, and improving or maintaining functional independence.”

Further: “… physical exercise is free, reduces the risk of many potentially lethal diseases, and helps strike the increasing sedentary behavior and physical-inactivity pandemic. Within this line, although exercise does not mitigate the aging process, it attenuates many of the deleterious systemic and cellular effects and improves the function of most of the mechanisms involved in aging” 

Over and over, research demonstrates that exercise “exercises” a positive influence over metabolic syndromes – described as those who have:

  • Large waist
  • Low levels of HDL (“good”) cholesterol
  • High levels of triglycerides
  • Elevated blood pressure 
  • Elevated fasting glucose (blood sugar) levels.

Beyond exercise, avoiding tobacco use is easy pickings, but one more area that we have control over and that also contributes to longevity is good dental hygiene and care. Periodontal disease can impact us in a number of negative ways.

Right. These are the ideas that I’ll leave you with today to think and ponder over.

Ask yourself: Do I have the desire to join in the Centenarian Olympics?

I’m asking myself a lot of questions and deciding which paths I’m willing to take to get there and where the risk/reward falls in my favour.

Within my own wheelhouse, the beast for me to tame is my lifelong sugar addiction… my personality should be sweet, but my oral consumption? Not so much!

Time to go… I’ll return in a future blog post to talk about promising medical and pharmacologic means of dealing with the 9 hallmarks of aging.

Grab your flashlight and let’s go on a fun search for the Fountain of Longevity and Healthspan.