Why Lifespan doesn’t = Healthspan
An intro to human longevity
Looking for the fountain of youth?⛲
For centuries humans have dreamed of immortality. When our loved ones are sick in hospital beds, we pray for just one more day.
But extending life isn’t enough when you're in chronic pain. I’d rather see my loved ones out of the hospital for as long as possible.
So where’s the fountain of health?
Global average life expectancy is over 70 years old, that’s double what it was in 1900!
But how many of those years are we healthy and free of chronic diseases?
A better question to ask is how long are we in optimal health conditions, how long is our healthspan?
The key to a prosperous life is increaseing healthspan, most of our health spans are only 75% of our life spans. As we age our bodies become worn out and more vulnerable to illnesses.
There isn’t a single pill to longevity💊, there’s multiple factors involved. Instead, we need to change our approach to target a combination of these areas:
- Senescent cells
- Stem cells
Zombie Cells infecting other cells: Senescent cells🧟
In order to reproduce our cells divide in a process called mitosis. After going through mitosis 50 times they turn into these zombies called senescent cells, they are still alive but don’t make any new tissue, they’re chilling.
They accumulate as we age. As a baby👶, we have barely detectable amounts of senescent cells but older folks👵🏻 have tons of these trouble makers.
Their correlation to longevity was discovered when scientists we’re running tests against cancer on mice by turning off a gene called BubR1. What they noticed was these mice aged rapidly by 3 months old they had a bunch of diseases. They took a closer look at these mice and noticed they had accumulated numerous senescent cells.
When researchers removed these zombies they lived up to 25% longer!!
But why are senescent cells so bad?
While they’re chilling, they cause inflammation to nearby cells. The immune system tries to clean them out but over time it gets harder to hunt them down, as a result, they build up.
So why not just make a drug to attack senescent cells? It’s not that simple, there’s a different type of senescent cell for every type of tissue. The way the immune system hunts things down is by using these identifiers called biomarkers. But senescent cells have different biomarkers for every type of tissue they came from.
Senescent cells may even be helpful for repairing damage, as researchers found that mice without them took longer to heal from wounds.
Researchers are looking into senolytic, a compound that selectively kills these cells.
DNA caps protecting chromosomes: Telomeres
A senescent cell is a cell that can’t divide anymore, but why does this happen?
Our DNA is coiled up in chromosomes, to replicate themselves they divide undergoing a process called mitosis, when this happens our chromosomes get shorter uh oh… No worries our DNA is protected by these little caps on their ends called telomeres. Telomeres are just extra repeats of our DNA, it’s okay if we lose these.
But we run into trouble when the telomeres are gone, now our important DNA is exposed, as a result, the chromosome will deteriorate leading to… senescent cells.
Cellular senescence is around 50, meaning the cell can undergo mitosis 50 times before it’s telomeres die out. This is also known as the Hayflick limit.
Telomere shorting is a natural process by our bodies but can be accelerated due to factors like stress. (Stress is literally killing you)
We know there's an enzyme called Telomerase that slows down telomere shorting, but can also increase the chances of cancer(cells dividing uncontrollably).
Increasing telomere length by 10%
Telomerase regulates telomere health during reproduction in stem cells, the active component is TERT. Ramunas Yakubov leads a team that discovered a method to increase telomere length by up to 10%.
They added 3 applications of modified TERT mRNA. Increasing telomere length by 1,000 nucleotides(a single nucleotide is 3 DNA bases of either A/T/C/G). Of the cells, they treated skin cells were able to divide an additional 28 times, while muscle cells divided 3 more times.
Superhero cells: Stem cells
Stem cells are superpowered because they can turn into any type of cell, but before they transform they’re just cells without a specific function, they’re undifferentiated.
We can use stem cells to replace worn-out cells for example, we replace the entire lining of our intestine every 4 days!!
There are 3 main types of stem cells:
- Embryonic/ Pluripotent: can turn into any kind, formed during the blastocyst phase of embryonic development.
- Induced Pluripotent: are regular stem cells that are modified to act like pluripotent stem cells.
- Tissue-Specific/adult stem cells: limited to replacing existing cells
Right now medicine is very general, but we’re seeing a shift to personalized health care. Companies are interested in using our own bodies' stem cells to repair damaged tissue, this field is called regenerative medicine.
Patients with Leukemia(where bone marrow is crowded with cancer cells) can be treated through stem cell transplants, the cells turn into blood cells to repopulate the bone marrow.
At around 25 our stem cells start to turn off. When you’re a kid a broken finger will heal up in a couple of months, but for an 80-year-old it’ll have a huge blow on their lives.
Nad+, Nicotinamide Adenine Dinucleotide
Nad is a co-enzyme that helps out with a ton of reactions, it activates enzymes in the nucleus to protect DNA.
DNA is like a thread, sometimes it gets tears in it, to fix these tears we have a compound called PARP1. Buttt PARP1 is deactivated by DBC1. No worries Nad+ comes in and kicks the DBC1 out, enabling the PARP1 to fix the damaged DNA strands.
By age 50 our body has half its original amount of NAD, this is a problem because NAD helps our cells communicate.
In a study by Harvard medical, researchers put NAD droplets into the water of old mice, in a week they noticed significant changes in DNA repair and even stopped DNA ageing.
So how do we get more NAD+?
There’s a couple of precursors(ways to get) to NAD: Nicotinamide (Nam), Tryptophan (Trp), Nicotinic Acid (NA), Nicotinamide Mononucleotide (NMN).
The most efficient is NR (Nicotinamide Riboside). Certain companies are selling NR supplements such as MetroBiotech.
By 2025 the longevity field could be worth over $600 billion, big players include:
Unity biotechnology developing drugs to target specific diseases targeting senescent cells, backed by Jeff Bezos fund and Peter theil
MetroBiotech, testing human-grade NAD, they’ve already made nicotinamide mononucleotide (NMN), which naturally is found in small does in broccoli and avocado. They see use cases in protecting cancer patients during radiation treatment
Elysium Health created Basis, a boaster for NAD+, its a combination of 2 natural compounds, pterostilbene (found in almonds and grapes)and nicotinamide riboside(found in cheese and yogurt).
Celulairty clinical-stage allogeneic cell therapeutics company using postpartum placenta raised 250million and backed by Peter Diamandis. 1 placenta =1000 doses. Umbilical cord banking has been around for a while but The placenta can be used in any person, unlike other organ transplants which the body can reject.
Key takeaways 🔑
- We should aim to increase human healthspan not just human life span
- The best path to longevity is a one-stop solution rather a combination of therapies
- Stem cells are unspecialized. they can be used for regenerative medicine, There’s induced pluripotent, embryonic and adult stem cells.
- NAD+ helps aid DNA repair and cell communication, we have smaller levels of it as we age.
- Senescent cells do not create new tissue, cause damage and inflammation to surrounding cells. We have more of these as we age.
- Telomeres are protective DNA caps on chromosomes, they shorten each cycle of mitosis. They can do this about 50 times before turning into senescent cells(Hayflick limit)