Is All This Talk About Aging Getting OLD?

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??

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

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.