Tuesday, February 2, 2016

Uncertain Health in an Insecure World – 74


“Increasingly Poor Decisions”


IFC’s television comedy (2010-2012), The Increasingly Poor Decisions of Todd Margaret, followed the doomed business fortunes of an American in London, selling the dubious energy drink, Thunder Muscle.  New to sales and British culture, with a single employee, the situation isn’t helped by the fact that Todd is also a pathological liar. Arrested for lewdness, pardoned by influence, with his American citizenship revoked, Todd ends up in the only country that will accept him – North Korea! In exile, Todd manipulates The Supreme Leader, and ends up pushing the nuclear launch button, resulting in a post-apocalyptic finale.


Funny mistakes, eh…

Make no mistake. It’s the decisions we do or don’t make as we age that cause the common signs & symptoms of aging. In fact, the associations of aging – weight gain, memory loss, lack of energy, wrinkled skin, and chronic illness – are not simply the result of the passage of time. Sedentary living, lack of sleep, poor diet, and insufficient skin care are the increasingly poor decisions that we can proactively chose to not make.


Aging is not a disease – it is a physiological process.

But if you Google the term, “reverse physiology”, you’ll be repeatedly directed to “reverse psychology”. If you dig a little deeper into the body of anti-aging science, you too may become convinced that aging physiology can be slowed, and actually reversed! Whether interventions can actually reverse aging, or are simply restoring healthy aging processes, is hotly debated. 

Unfortunately, many of us become so zealous or impatient that we resort to increasingly poor decisions – extreme exercise regimens, severe diets, hormones or stimulant drugs, and cosmetic surgery – often with counterproductive side effects after short-lived benefits. Research shows that these quick-fix strategies are not sustainable – lies that are counterproductive to underlying human physiology.

Some scientists think the cellular pathways to cancer are also part of aging.

With aging, nuclear and mitochondrial DNA communicate less effectively, adversely affecting cellular energy production. In 2013, Harvard Medical School researchers showed that increasing the level of a protein which helps cellular DNA signaling reverses aging in mice by >75% over two years. In human longevity terms, this would equate to 60 year old cells reverting to 20 year old cells!


The term epigenetics was first coined by Conrad Waddington in Nature (1942).


Epigenetic modifications to DNA methylation and to histone protein acetylation in gene chromatin are thought to affect RNA transcription (below), negatively impacting memory consolidation and synaptic plasticity. Chromatin structure is highly dynamic, and is integral to effective transcription. High frequency synaptic patterns activate NMDA receptors, causing a calcium influx which activates ERK. ERK regulates several genes by altering transcription factors essential to memory formation. The systemic administration of sodium butyrate (NaB), which increases histone H3 acetylation, rescues certain maze-solving cognitive functions in older rats and memory formation in juvenile snails.



Declining memory and cognitive ability are linked to altered gene expression in the human brain’s hippocampus and pre-frontal cortex. Some rare childhood neurodevelopmental conditions are caused (in part) by genetic defects in DNA methylation (MECP2 gene in Rett Syndrome) and histone acetylation (FMR1 gene in Fragile X Syndrome).


The basic metabolic rate (BMR) reflects total body calorie utilization at rest.

BMR is another physiologic marker which declines with age – by 2% per decade after 20 years of age. Humans lose 30% of total muscle cells between ages 20 to 70! As muscle mass decreases in middle age (i.e., sarcopenia), the resting need for oxygen and calories for muscle contraction declines. Regardless of age, adding lean muscle mass increases BMR, although aging still reduces BMR independent of muscle mass. And dieting to lose fat without exercise to build muscle is completely ill-advised.


If middle-aged persons eat the same number of calories that they ate at age 20, fat begins to build up, leading to obesity. The average 65 year old sedentary woman has twice the percent body fat of her 25 year old counterpart (43% versus 25%). For men, the corresponding figures are 38% versus 18%. Central body fat accumulation is particularly dangerous. Australian, Canadian and U.S. diabetes prevention programs have shown that lifestyle changes such as physical activity, weight loss, and de-stressing maneuvers (i.e., yoga, deep breathing, stretching, tai chi) delayed or prevented obesity-related type-2 diabetes, especially in those aged >60 years.

Many scientists believe that aging is a phenomenon unique to humans and domesticated animals.

Aging is defined as the accumulation of diverse deleterious cell and tissue changes (loss of homeostasis) that contribute to the increased risk of disease (pathology) and death. The major domains of research into the causes of aging are free radical damage, altered immunity, increased inflammation, and mitochondrial dysfunction (see above). Aging is likely multi-factorial, with each of these pathways being altered in different ways and to varying degrees.

Most scientists have long viewed the physiologic process of aging as immutable.


But many scientists have studied reversing aging physiology. One of the physiologic markers of aging is heart rate variability (HRV), which reflects a delicate balance between the health of the parasympathetic and autonomic nervous systems. HRV changes during breathing, postural shifts and sleep are primarily controlled by the vagal nerve, which loses function with advancing age. The related loss of HRV is a predictor of higher cardiovascular death rates (often sudden cardiac death). In autoimmune diseases such as diabetic neuropathy, and with the infiltration of fatty deposits into the carotid artery near the vagal nerve, blood vessel inflammation reduces HRV. Regardless of weight loss, HRV changes independently predict type-2 diabetes development in pre-diabetics.

You can’t manage what you can’t measure. Wearable fitness tracking technology has exploded!



There are dozens of commercially available wearables and mobile device apps that capture heart rate “little data” 24/7. Some can even record a medical grade ECG tracing. A few can derive HRV data – Hexoskin, OMSignal, Scanadu Scout, Zensorium Tinke, etc. The safe but not yet FDA-approved Thync device (above), worn on the temple where its impulses activate the adjacent central nervous system, increases alertness in a fashion compared to “digital Red Bullor produces relaxation when operating in “chill vibe”. Placing the FDA-approved Quell wearable device (below) on the calf of patients with chronic pain sends neural signals from the peripheral to the central nervous systems, releasing natural pain-relieving natural opioids – neuropeptides called enkephalins. Quell also tracks disrupted sleep patterns, which improve as pain is diminished.


Can we discipline ourselves to lead healthy lifestyles, which if sustained, have demonstrable anti-aging benefits in the long run?

Individual confidence is a big part of good decision-making. Todd Margaret had low self-esteem issues.

In the Square, there is growing confidence in the empowering science and technology of “reverse physiology”.            

And we're not laughing at increasingly poor decisions any more!

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