Unbundling Sirtuins, aka the longevity proteins
Everyone has their favourite longevity pathway. Dr. David Sinclair's favourite is Sirtuins. Let's unbundle the seven sibling Sirtuins, SIRT1-SIRT7. What do they do and how can we intervene?
👋 Hola! Welcome to Out of Singapore. I write this newsletter every Sunday on topics that I come across. As part of my current work, I get information on longevity - the science of living longer, maybe until 120 or 140 years. I see it as an effort to be a productive human for longer (maybe work till you are 90). Yes, longevity will create many new social issues to deal with. On the plus side, it will prevent another “Biden” as president of USA or any other country.
Today, I will cover
What are Sirtuins?
What do we know about the seven siblings?
How can you activate Sirtuins?
Before I move forward, please note this - I am not a medical professional. I work with researchers and medical professionals. My source of information is conversation with experts and internet research. Please do not consider any information here as medical advice. Longevity is an evolving research area. We are all learning together. Please speak to your Doctor for any medical advice.
Okay, now let’s forward.
#1 What are Sirtuins?
Sirtuins are a family of proteins that play a crucial role in regulating cellular processes related to aging, metabolism, and stress resistance. Sirtuins are involved in DNA repair, gene expression, and mitochondrial function, among many other cellular functions.
In simple terms, Sirtuins are longevity proteins. They are produced or activated by NAD+ in our cells. They help maintain homeostasis (cellular balance).
There are seven sirtuin proteins. The are named as SIRT1, SIRT2, SIRT3, SIRT4….SIRT7. The most known, studied and common sirtuins are (source) -
SIRT1
SIRT3
SIRT6
Note this - “Notably, this protein family plays a important role in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a potential therapeutic target for pathologies including cancer, cardiovascular disease, respiratory disease, and other conditions.“ Source: The sirtuin family in health and disease
However, sirtuins are controversial. They are new class of proteins discovered as recent as 1980s, most research happened after 2000s. There have been conflicting studies, and a bad saga over claims that resveratrol activates sirtuins. GSK lost $700 mn due to this in 2010. Here are some publications which capture controversies about Sirtuins. Do read them when you are free.
The field of longevity needs counter arguments to survive and come up results that accepted by larger part of the population.
Now, let’s look at what function these longevity proteins play.
#2 Functions of the seven longevity siblings
I have updated my longevity spreadsheet document with information on Sirtuins (captured in a new tab). Here is the summary screenshot of the roles played by each sirtuins.
To summarise,
SIRT1 regulates aging, mitochondrial function and cholesterol. The benefits of SIRT1 are in increased lifespan, better metabolic health and stress resistance.
SIRT2 regulates cell cycle, tumour suppression and neurodegeneration. It’s benefits are in neuroprotection and metabolism regulation.
SIRT3 regulates mitochondrial function, energy production and manages oxidative stress. It helps improve mitochondrial function and strengthen stress resistance.
SIRT4 regulates insulin secretion and fatty acid oxidation. It helps regulate insulin and metabolic health.
SIRT5 is involved in urea cycle, fatty acid metabolism and amino acid metabolism. It improves mitochondrial function.
SIRT6 is involved with DNA repair, telomere maintenance, glucose and lipid metabolism. It benefits are in DNA health, and extended lifespan.
SIRT7 is involved in DNA repair, stress resistance and tumour promotion. It improves stress resistance, ribosomal biogenesis (DNA synthesis) and genomic stability.
While all of them are important, SIRT1, SIRT3, SIRT4, SIRT6 and SIRT7 looks most important for extended and healthier lifespan. What do you think?
Here is tabular summary for your reference.
#3 How to activate sirtuins?
Sirtuins are activated by biochemical processes in our body normally. However, with aging and lifestyle choices, they become subdued. How can you potentially activate these proteins to ensure you are healthy? Here are some ways
Caloric Restriction - Fast, eat less, eat within small fixed time window.
Exercise - Increase physical activity, lift weights, walk, run, play, laugh.
Diets like ketogenic diet, fasting and intermittent fasting.
NAD+ precursors like NR and NMN.
Flavonoids like Fisetin and quercetin.
Most of these don’t need external stimulation. If you can fix your food, lifestyle and physical activity, you are doing great!
The world is going gaga over sirtuins as they have shown promise of increasing lifespan in research studies. Has it been established as non-disputable scientific fact? Unfortunately, not yet.
Thanks for reading again. I understand that these topics may not be relevant for readers. It took me more than a year to make a sense of this science. Even now, I am generally confused and trust the scientific wisdom shared in research papers. There is belief that there will be a breakthrough one day. One day, one of these papers will find something interesting that will change how we age.
If you don’t vote any option, I would assume the answer is “no”.
Thanks again, please do like the post if you felt this was a good read. 😍
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Please note that I may not write next week as I am travelling. If I find time to write, I will pen down something short and punchy (like me 🤣).
Have a great week ahead. 🍻