Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement

#1

A reasonably good overview of the scientific momentum in biology of aging research…

The growing social and economic concern of an aging world population has catapulted aging-related research into the spotlight. Indeed, over the past decades, progress in medicine has powered a significant increase in life expectancy worldwide. Thus, more than 2 billion individuals are expected to be older than the age of 60 by 2050. (1) This demographic milepost will come with a major increase in age-related diseases, such as Alzheimer’s disease, cardiovascular disorders, and cancer, which effectively double in incidence every 5 years passing the age of 60. (2) The relationship between aging and these diseases has triggered fundamental research into the aging mechanisms and approaches to attenuate its effect.

Aging is broadly defined as a gradual functional decline in the living organism’s intrinsic ability to defend, maintain, and repair itself in order to keep working efficiently and has attracted attention throughout the history of civilization. (3,4) The health and survival of an organism present a dynamic equilibrium between the processes of damage and repair, alteration, and maintenance, a conventional concept of which is homeostasis. This concept, recently replaced by homeodynamics, involves the constantly changing interrelations of body constituents while an overall equilibrium is maintained. (5) Thus, aging is characterized as a multidimensional process involving a gradual contraction of homeodynamic space. It affects many different aspects of life including physical health, cognitive functioning, emotional well-being, and social relationships. There is a consensus that aging is associated with two key aspects: (i) the progressive decline of numerous physiological processes, such as the body’s ability to accurately regulate homeostasis, and (ii) the enhanced risk of developing severe diseases such as cancer or cardiovascular disease. However, while aging is a major risk factor for many chronic diseases, it is important to recognize that aging and disease are not synonymous. Many older adults maintain good physical and mental health well into old age, and there is growing interest in promoting “successful aging” by focusing on factors that contribute to overall health and well-being. (6,7)

Researchers have distinguished between two categories of age: the chronological age based on the birthdate, and the biological age, which measures the true age at which the cells, tissues, and organs appear to be, based on biochemistry. (8) While it is impossible to alter the chronological age, there are ways to manage biological age. Since aging is influenced by multiple factors, including genetics, lifestyle aspects such as diet, exercise, and stress, environmental factors such as pollution and climate change, and social factors such as social support and socioeconomic status, interventions such as lifestyle adjustments, medical treatments, and social programs can help promote healthy aging and extend the lifespan. Understanding the complex interactions between these factors is essential for promoting healthy aging. (9)

Along with the whole organism, the functional capabilities of the brain gradually degrade upon aging, manifesting as declines in learning and memory, attention, decision-making capacity, sensory perception, and motor management. The aging brain exhibits significant indicative signs of impaired bioenergetics, weakened adaptive neuroplasticity and resilience, anomalous neuronal network activity, dysfunctional neuronal calcium homeostasis, accumulation of oxidatively modified molecules and organelles, and inflammation. (10−16)Reduced number and maturity of dendritic spines in aging organisms, along with alterations in synaptic transmission, may indicate abnormal neuronal plasticity directly related to impaired brain functions. (14) At worst, neurodegenerative and cerebrovascular diseases, which strongly damage the basic functions of the brain, may develop. Thus, age-associated alterations render the aging brain vulnerable to degenerative disorders including Alzheimer’s and Parkinson’s diseases, stroke, and various kinds of dementia. (17,18) While currently there is no cure for these age-related brain disorders, early detection by recognizing symptoms can help slow the progression of the disease.

cn3c00531_0001

Figure 1. Yearly growth of the number of aging-related documents (journal articles and patents) in the CAS Content Collection.

Full, Open Access Paper:

https://pubs.acs.org/doi/full/10.1021/acschemneuro.3c00531

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#2
#3

This video perfectly defines what I have experienced after age 80. Fortunately, rapamycin and other supplements mentioned in various threads have mitigated the symptoms.

Yes, food tends to taste like crap, and that is why many seniors become underweight and frail. (Change #5) This is my primary struggle. Fortunately, I live in a state where cannabis products are legal. I take a 25 mg indica THC tablet every afternoon, about one hour before my evening meal. While it doesn’t give me the pot smokers’ munchies, it definitely increases my appetite and allows me to gain some weight back.

Even though I take rapamycin, wounds still seem to heal at an acceptable rate (Change #4).

I am working to slow down change #3. I think that rapamycin and galantamine help.

Rapamycin and exercise have brought sarcopenia to a virtual standstill. (Change #2)

Change #1 is under control; my sleep hygiene and supplement stack allow me to sleep well.

The Age of 80 Marks Biological Transformation: By age 80, the body undergoes significant changes, as it shifts from performance to survival mode, prioritizing basic functions over complex ones.

Five Irreversible Changes: Research indicates that there are five major biological transformations that all humans experience once they reach 80.

  • Change #5: Taste Buds Shrink: By age 80, the body loses nearly 70% of its taste buds, leading to less enjoyment of food and an increased risk of hypertension and diabetes as a result of compensating with more salt and sugar.
  • Change #4: Skin Struggles to Heal: As we age, skin loses its ability to repair itself, with wounds taking longer to heal due to a decline in fibroblast function and collagen production.
  • Change #3: Brain Rewires Itself: The brain loses 20% of its white matter by age 80 and starts rerouting neural pathways, which can cause slower thinking and memory lapses, but also prioritize emotional memories.
  • Change #2: Muscle Atrophy (Sarcopenia): By age 80, the body begins consuming its muscle tissue for energy, leading to sarcopenia, which weakens muscles, making balance and immune function harder to maintain.
  • Change #1: Disrupted Sleep Cycle: The circadian rhythm begins to break down, leading to sleep disturbances, where people may wake up in the middle of the night and feel tired during the day.

Executive Summary:

As people cross into their 80s, their bodies undergo five significant, irreversible biological changes. These include the shrinking of taste buds, slower skin healing, brain rewiring, muscle atrophy, and disrupted sleep cycles. While these changes can be alarming, they are part of a larger survival strategy employed by the body. The aging process doesn’t signify breakdown but rather a shift in the way the body operates, adapting for survival rather than performance. Recognizing and adapting to these transformations, such as managing muscle loss and sleep irregularities, can improve quality of life in later years.

:hourglass: Timestamps:

:stopwatch: Intro - 0:00

:dna: Change no.5 – 01:40

:dna: Change no.4 – 04:47

:dna: Change no.3 – 08:01

:dna: Change no.2 – 10:39

:dna: Change no.1 – 13:38

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#4

It’s great that you have mitigated most of these issues to at least some extent - an example for us all to follow!!

#5

My PCP says that another dramatic change occurs at age 85, which he described as “going off a cliff,” by which he meant that that setbacks are no longer followed by comebacks, that the aged don’t fully recover from illness and injury.

#6

Let’s hope rapamycin and other life extension protocols prevent that.

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#7

I think I’d be zonked on 25, but maybe tolerance changes with age along with all the other changes. I take 10 or 15 mg to enhance my running music, but I’ve noticed recently that the effect has diminished somewhat.

#8

For some reason I am a low responder to THC. Two beers gives me more of a buzz than 25 mg THC.

Oral THC half-life
"THC has a complex elimination profile with multiple half-lives, but studies show a long terminal half-life that increases significantly with repeated use.
For occasional users: The terminal half-life of THC is estimated to be 1 to 3 days.
For chronic daily users: The terminal half-life can be much longer, ranging from 5 to 13 days or more, because THC builds up in fat tissue."
“Lower bioavailability: Oral THC has a much lower bioavailability than inhaled THC (estimated at 4–20% versus 10–35%). This is because it undergoes significant “first-pass” metabolism in the liver before entering the bloodstream.”

So, I tried cutting the tablets in half so that I am now using 12.5 mg daily. This seems to be just as effective for appetite stimulation and produces a mild mood boost without significantly affecting brain function.

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#9

A half-life of 5-13 days means that I’m permanently stoned.

#10

You don’t feel permanently high on daily oral THC because:

  1. THC has multi-compartment kinetics: psychoactive levels in the brain fall within hours as THC rapidly redistributes out of the brain into blood and fat—even though a tiny tail lingers in fat for days.
  2. The effect tracks the effect-site (brain) concentration, not the low, lingering plasma/fat “tail.” This creates a pronounced peak (hours) then a steep fall in effect, despite detectability for days.
  3. With daily dosing, you reach a steady state of low background levels, but not a steady state of intoxication, because CB1 receptors desensitize/downregulate (tolerance) and then resensitize overnight. [4. Oral dosing makes more 11-OH-THC (potent, short-lived in the brain), giving a strong but finite window of intoxication after each dose.
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#11

Is your galantamine a supplement or a far more costly Rx? Do you use it in addition to choline, a supplement you once recommended that indirectly increases acetylcholine? And what about hupercine A, an inexpensive supplement that inhibits acetylcholine breakdown?

Thanks

#12

I got my supply from India. Unfortunately, I did not order a large enough supply to last through the current tariff fiasco.
I was taking 16 mg/day, but now I have cut back to 8 mg/day to stretch my supply.
When I ordered the galantamine tablets, I also ordered:

Rivastigmine: increases the level of acetylcholine, a neurotransmitter important for memory, attention, and other cognitive functions.
Memantine: an N-methyl-D-aspartate (NMDA) receptor antagonist. It helps regulate a brain chemical messenger called glutamate, which plays a role in memory and learning.

So far, I have tried memantine, which gave no subjective benefits. Galantamine works for me. It definitely clears up some brain fog. I had forgotten I even had rivastigmine, which I haven’t tried yet, but since it also increases acetylcholine levels, it might be a substitute for the galantamine. I will add some to my daily memory stack.

Huperzine A: It works by inhibiting the enzyme acetylcholinesterase, which allows for increased levels of the neurotransmitter acetylcholine in the brain.

I never felt any subjective benefits from huperzine A; maybe I just wasn’t taking enough. In any case, I never reordered when my supply ran out.

Also, I experienced no unwanted side effects from memantive and galantamine.

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