Greetings everyone!

This is your host, Ralph Sanchez.

Today I am finally delivering on a preview note from my last episode in which I promised to provide an overview on what it takes to become a cognitive super-ager and truly live younger, longer.

Thus, I am very much looking forward to bringing you this review here today with regard to longevity and healthspan, and what more specifically underlies the capacity for anyone to attain a cognitive super-ager’s health and wellness lifespan (healthspan) if you think ahead.

The science of getting older (gerontology), and the biology of aging has spurred an immense interest and research effort that centers on the biochemical, molecular, and indeed the related senescent cellular changes that underlie age-related diseases.

And, the term "super-agers" has emerged as a handy expression to reference long-lived individuals that seem to weather the damaging brain aging processes associated with cognitive impairment. and retain a superior cognitive performance in later life.

According to study recently (2023) published in The Lancet Longevity Journal, super-agers are "people in their 80s who have the memory function of people 30 years younger".

So what is their secret?

Well, as all of you most likely know by now, numerous studies have asserted that the fundamental and healthy diet and lifestyle habits that nourish an optimal healthspan are requisite elements for life extension wellness and our brain health span.

Indeed, diet and lifestyle habits—that includes social enrichment—are often cited as keystone longevity pillars of long-lived centenarians of "Blue Zones"—5 or more specific regions around the world in which people achieve exceptional healthspans.

There is also a wealth of research that links a host of longevity genes to a longer lifespan and recent research indicates that genetic factors that influence longevity are particularly important the older you get (oldest old).

And, a number of studies have also determined that cognitively healthy centenarians are protected against Alzheimer's disease by a host of protective genes and their associated variants (genetic variants).

While the nature-nurture axis has some recognizable and potentially very modifiable pieces to the longevity puzzle, the science behind it all keeps revealing the secrets that not only allows for some fascinating insights, it also provides us all with a wellspring of knowledge which enables us, to some extent, to control our destiny.

One very important link that bridges the environment (nurture) to our innate potential (nature) is the emerging science of epigenetics—or the epigenetic modifications that are critical mechanisms in the dynamism of what I define as the “epigenetic bridge”.

Indeed, epigenetic mechanisms are a critical epigenetic bridge in upstream and core hallmarks of aging—dysregulation of epigenetic mechanisms (e.g., methylation, acetylation), accelerated telomere shortening and attrition, and genomic instability.

And those 3 hallmarks of aging all reflect the interrelated genomic and epigenomic determinants that are a critical component of accelerated aging processes.

However, there are 9 other hallmarks of aging that also must be taken into account when evaluating health assessments over the course of a healthspan.

Please listen in to this Cognitive Super-agers episode for the rest of story with regard to the hallmarks of brain aging, and how you can leverage that vital information for living younger, longer.

Fair warning … this review is lengthy and filled with the science backed research on epigenetic mechanisms and the Hallmarks of Aging.

Sincerely,

Ralph Sanchez, MTCM, CNS, D.Hom

BrainDefend®
https://www.TheAlzheimersSolution.com

https://www.facebook.com/TheAlzheimersSolution/
https://www.linkedin.com/in/ralph-sanchez/


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Episode #22—Where We Left Off

I’ll begin this episode by sharing an excerpt of the primary outcome from study #1 that I reviewed in part #1—#22—of this two part episode series.

In that study, the authors found “a positive association between OC [plasma osteocalcin levels] and working memory capacity, executive functioning and global cognition scores.”

Study #2—Excerpt

The authors of study #2 remarked “we observed that in both older adults with osteopenia and older adults with AD [Alzheimer’s disease] as compared to cognitively normal participants, BMD [bone mass density] values were lower and were associated with the severity of cognitive impairments.”

And, "that BMD could identify AD participants with high accuracy”.

Study #3 —Excerpt

Bone loss biomarkers were analyzed, and a key DEXA scan (dual-energy X-ray ) finding from the study revealed that: a lower bone mineral density is closely associated with early-stage AD in male patients.

Study #4—Excerpt

In the review of study #4 of this two-part episode series, analysis of data drawn from 3,651 participants from a sub-study of the Rotterdam Study found that the participants that had a lower BMD [bone mineral density] had a twofold higher risk over those with a higher BMD of developing dementia.

Lastly, in episode #22, I quoted the lead author of the 2016 study, Christine Dengler-Crish, who stated “Measurement of bone density, which is routinely performed in the clinic, could serve as a useful biomarker for assessing AD risk in our aging population.”

Gut-Bone-Brain Axis—Excerpt

A significant body of research that has amassed over the past 20 years and more, and several key and recent studies have shown that the gut microbiota and the short-chain fatty acids (SCFAs), such as butyrate that are metabolized from fiber (resistant starches) fermentation play a role in regulating bone homeostasis (bone resorption and formation).

A very recent study concluded that “Our findings indicated that there were remarkable changes in gut bacteria, fungi, and fecal metabolites in postmenopausal women, and such changes were notably correlated with patients’ BMD (bone mass density) ​​and clinical findings.”

Estrogen in the Bone-Brain Axis—Excerpt

Estrogen—RANKL-RANK Pathway

I’ll now close out this episode with a review of a couple of key risk factors linked to estrogen, and how it all fits into the bone-brain axis.

A key pathway in which estrogen modulates bone remodeling is represented by a key regulatory factor in this bone remodeling phenomena—the receptor activator of Nf-kB—or its acronym—RANK.

Estrogen is a critical yin regulator of inflammation associated with osteoporosis and many other health conditions in a women’s body and brain.

Estrogen’s regulatory effect on inflammation—a yin force— counters and naturally buffers the inflammation pathway of RANKL and RANK—the yang element in this duality.

Tune in to hear the rest of the details and episode!

Thanks, and God Bless!

Ralph Sanchez, MTCM, CNS, D.Hom

BrainDefend®
www.TheAlzheimersSolution.com

https://www.facebook.com/TheAlzheimersSolution

https://www.linkedin.com/in/ralph-sanchez

https://www.instagram.com/alzheimers_solution

Hello once again!

This is your host Ralph Sanchez, and welcome to episode #22 and indeed, it has been much too long between this episode and the last one.

I have been busy with new book projects on the key underlying risk factors for late-onset Alzheimer’s disease that are unique to women.

I’ll have an announcement on when those books will be available here soon, and frankly, I'm looking forward to doing so.

And on that note, I have in store for you another special episode today in which I’ll present the evidence and the rationale for the bone-heart-brain axis as it pertains to an increased risk for dementia and late-onset Alzheimer’s disease (LOAD), and why age-related bone loss may be an indicator of an increased risk for LOAD.

Bone is an endocrine organ

Several key studies over the past 15 to 20 years have demonstrated that the human skeleton is an endocrine organ that bidirectionally communicates with our brain and our gut and other organs.

Normally, one may think of typical endocrine organs such as the pancreas, thyroid or pituitary gland which produce and release hormones that regulate a myriad of functions in the body and brain.

Well, the same can be said for bone, which secretes the hormones—FGF23 (Fibroblast growth factor-23) and osteocalcin—a peptide hormone.

So let's dive right in to that osteocalcin overview.

Osteocalcin—Heart and Brain Health

To begin with, a seminal study published in 2007 by Dr. Gerard Karsenty, has set in motion numerous studies since which have expanded on these endocrine and metabolic linkages between a form of osteocalcin—uncarboxylated osteocalcin (ucOC)—and other organs.

Indeed, bone cells (osteoblasts) secrete a form of a bone protein/hormone—osteocalcin (and others)—which is normally associated with the maintenance of bone mass, and it also functions as a key protein/hormone in the crosstalk and regulation of physiological pathways between bone

A modified form of osteocalcin, uncarboxylated osteocalcin (ucOC), easily crosses the blood brain barrier, and it has been shown to an essential hormone in fetal brain development, and in the regulation of mood and cognition throughout life.

Uncarboxylated osteocalcin that is associated with insulin resistance and cardiometabolic disease (metabolic syndrome, type 2 diabetes).

Uncarboxlated osteocalcin in turn regulates insulin secretion in pancreatic islet cells which underlies the regulation of glucose homeostasis by bone.

Thus, this bone-insulin dynamic is termed the bone-pancreas endocrine loop.

In a collaborative research effort and study published in 2017, Dr. Eric R. Kandel, a Nobel laureate (Nobel Prize for Physiology or Medicine in 2000) and senior researcher at Columbia University / Howard Hughes Medical Institute, and Dr. Karsenty, reported on a key hippocampal receptor— Gpr-158—that binds with osteocalcin and mediates hippocampal memory formation.

The study also reported another significant finding with regard to the benefit of how osteocalcin mediated “a molecular pathway critical for hippocampal-dependent memory” by stimulating brain-derived neurotrophic factor (BDNF) transport to the synapses of hippocampus.

So much more with regard to the role of osteocalcin and uncarboxylated in part 1 of this bone-heart-brain axis episode, so please listen in for the rest of the story.

Episode #2 of the Bone-Heart-Brain Axis will be available soon so please look for it as it will include additional insights into this fascinating and important research and science.

God bless and goodbye.


Ralph Sanchez, MTCM, CNS, D.Hom.

https://www.TheAlzheimersSolution.com

BrainDefend®

https://www.facebook.com/TheAlzheimersSolution/

https://www.linkedin.com/in/ralph-sanchez/

https://www.instagram.com