Can Aging Be Slowed / Prevented / Reversed ?!

Mitul Saha
(Last Updated: 19 August 2023)

*

There is a lot of buzz on Internet about a 45 year CEO, trying to be 18 year old again.

The desire to retain / regain youth has been one of the greatest, since the dawn of human civilization.

The question is (in-fact, always has been) - where does Science and Medicine stand on this topic, as of today ?! Can aging be slowed / prevented / reversed ?!

These are what we try to answer in this blog.

What Is Aging?

Aging can be defined as "the time-related deterioration of the physiological functions necessary for survival and fertility", usually leading to illnesses of increasing severity over time (apart from common visual symptoms such as wrinkles, hair gray-ing & loss, etc).

What Causes Aging?

Aging is believed to be caused by a number of processes going awry, accumulating un-repaired damages (especially with time) in the cells of our bodies.

(Image courtesy Cell)

These processes include:
  • Genomic Instability: Our DNA is damaged million times a day (say, by UV radiation, mitochondrial dysfunction). Due to imperfections in cells, some of these are left un-repaired and those accumulate with time, leading to gradual deterioration in organ function (aka aging).
  • Telomere Attrition: Each time a human cell divides, a piece of telomere is lost. At some point the telomere length becomes so small that the cell stops dividing. These cells can then die or cause inflammation, accelerating the aging process.
  • Epegenetic Alterations : Histone proteins in our DNA can be altered by certain life-style habits (that include stress, certain diets & drugs), likely contributing to aging.
  • Loss of Prosteostatis : Proteins are the most important molecules in our cells (building block of life). Degraded / misfolded proteins accumulate with time (again, due to imperfections in the cell machinery) contributing to aging.
  • Disabled Macroautophagy: Macroautophagy disablement occurs when cells in the body are not able to perform self-cleaning. Processes such as, genomic instability (described earlier), can result in loss-of-function mutations in genes that regulate or execute autophagy. These result in impaired autophagy, which in turn contributes to aging (e.g., via cardiovascular / infectious / and neurogenerative diseases).
  • Mitochondrial Dysfunction : Mitochondria are like "power plants" of cells and also central hub for metabolic processes. Mitochondrial DNA accumulates mutations with age (say, via "Genomic Instability" described earlier). This also causes decrease in mitochondria efficiency overtime, contributing to aging.
  • De-regulated Nutrient-Sensing : Cells have nutrient-sensing pathways to ensure the body takes in right amount of nutrition (not too much, not too little). The regulation of these pathways get awry with time (say, due to "Mitochondrial dysfunction" described earlier), contributing to aging.
  • Cellular Senescence: The above processes may lead cells to become dormant over time (ceasing its normal function), contributing to aging.
  • Stem Cell Exhaustion: The above also happens to stem cells, hampering its efforts to keep our organs repaired / renewed, leading to organ aging, with time.
  • Altered InterCellular Communication: For proper functioning, cells need to recieve signals from neighboring cells and even from distant tissues (say, via blood). The signalling patterns can progressively go awry with time, contributing to aging. For instance, senescent cells (see above) start releasing signals which can cause other cells to go senescent as well. Also, with time, cellular damages along with debris from inflammation and metabolic processes acculate in and around cell, disrupting inter-cellular communication (especially, via "inflammaging").
  • Chronic Inflammation also contributes to aging. It is referred to persisting, longer-term immune response of the body, even when there is no "irritant" (e.g., viruses / bacteria / toxic chemicals). This could be due to hypersensitivity, auto-immune diseases, persistent irritant, deteriorating health condition, etc.
  • Dysbiosis: Changes in gut microbiome with time may also contribute aging - but it is not yet known how.

How To Measure Aging?

Chronological age (how many years one has lived) is actually NOT a good measure of aging. I am sure you have met people in their forties who look / act like in their early thirties (actor Paul Rudd ;)), and you have met people in their thirties who look / act like they are in their late forties. At the age of 85 (in 2018), Hiromu Inada completed the world championship Ironman - a feat unthinkable for most humans decades younger to him. There are many such examples, from throughout the human history. (How do they do it?? We will get to that ...)

So, instead of "chronological", scientists currently estimate biological age of a person via second generation "epigenetic clocks" - PhenoAge, GrimAge - and a third generation version known as DunedinPACE.

DunedInPACE is like an "aging speedometer". PhenoAge and GrimAge give more like a age snapshot.

Also, PhenoAge correlates with all-cause mortality, cancer, cardiovascular disease, and chronic respiratory disease. GrimAge is superior in predicting time to death and risk for coronary artery disease and cancer.

Pre-mature Aging - Causes & Prevention

Aging in one's body can get accelerated (aka pre-mature aging) because of:

Can Aging Be Slowed?

According to Science, yes, aging can be slowed, via:

Can Aging Be Prevented?

If aging can be reversed, then logically it can also be prevented. So, do see the Section: "Can Aging Be Reversed".

Can Aging Be Reversed?

Can aging be reversed or even just prevented completely? Science has not yet shown this, "definitively", in humans. But, there are already some preliminary encouraging results, which warrants continued scientific quest to reverse or prevent aging al-together:
  • In 2019, a small study on 9 people (aged 51 to 65, white men) showed that the biological clock can be reversed by ~2.5 years (!!!) via a cocktail of drugs (growth hormone, a diabetes medication, and a hormone supplement). This is a very promising breakthrough. But, at this point, this only means - more thorough study (involving larger and more diverse participants) is needed to confirm the findings, before this treatment can be made public. Studies would also investigate the potential of larger age reversals.
  • Using gene therapy (derived from cell-reprogramming techniques that won Nobel prize in 2012), researchers (Dr. David Sinclair and associates) were able to restore half of the lost vision in glaucoma plagued mice as well as turn back their biological clock to some extent. In follow up studies, from the same group, rejuvenation was also seen with brain tissue, kidney, and muscle. And, recently, they have now shown that similar approach also restores vision in monkeys as well. These are very promising developments! Now, as a next step - these studies need to be done on humans.
  • Exercise has the potential to reverse aging (1, 2, 3)
  • Supplements / Drugs (Metformin, Rapamycin, and Taurine are under investigation)

Final Words

(* Image by Freepik)