Dr. David Sinclair is a geneticist at Harvard Medical School as well as the co-founder and co-chief editor of the journal Aging. He is an inventor on 35 patents and has received more than 35 awards and honors. InsideTracker is proud to have him on the team as the chairman of the Scientific Advisory Board. 

Three years ago, Dr. Sinclair published his book Lifespan: Why We Age and Why We Don’t Have To. Lifespan quickly rose to popularity and has remained a must-read read over the years. 

This Q+A session with Dr. Sinclair (originally live on July 26, 2022) dives into a few of the most commonly asked questions from the audience. 

Intermittent fasting: Who is it for, who is it not for, and which blood biomarkers indicate it is right for you?

Dr. Sinclair believes that most people over the age of thirty do not need to be eating three meals a day, as this eating pattern often provides too many calories for the average person. Through rigorous scientific literature, it has been shown that the longest-living animals and humans do not eat constantly. “We need to get away from the idea that being a little hungry—and being without food for 15-18 hours— is a bad thing,” says Dr. Sinclair.

Dr. Sinclair elaborates that to be successful with intermittent fasting, you should continuously optimize biomarkers and track how this dietary pattern is impacting you as an individual. “This is why I was one of the first people at InsideTracker – I have always believed you need to measure things.”

In terms of specific biomarkers, Dr. Sinclair looks for improvements in blood sugar levels and decreases in inflammation. To do so, he pays close attention to fasting blood glucose, HbA1c, hsCRP, and cortisol. “It is also important to make sure you are not deficient in anything—specifically, B vitamins, magnesium, and sodium, says Dr. Sinclair.

*Please note, intermittent or prolonged fasting is not for everyone—individuals who are underweight, under 18 years old, pregnant or breastfeeding, have a history or currently struggle with eating disorders, and those with diabetes or on certain medications should refrain from intermittent fasting. Before beginning intermittent fasting, we recommend consulting with a doctor or dietitian to see if it’s appropriate for you. 

Which specific biomarkers do you track over time for longevity?

Dr. Sinclair played a key role in helping InsideTracker put together the InnerAge 2.0 calculations, and he feels that all the biomarkers included in that calculation are indicative of aging. However, there are some key markers he pays special attention to including blood sugar levels and albumin.

As we age, our bodies typically become less sensitive to insulin. “One way to extend life is to keep optimal blood sugar levels rather than watch them [levels] creep up with age,” says Dr. Sinclair. For this reason, he regularly measures fasting blood sugar and HbA1c.

Dr. Sinclair also explains the importance of albumin. Albumin levels decline with age and are correlated with longevity. “I have a theory that old and damaged albumin is toxic to the body, and may be one the reasons that having plasmapheresis is seemingly very healthy for animals,” he postulates.

How are resveratrol supplements associated with the aging process?

Resveratrol is a plant polyphenol naturally found in grapes, red wine, cocoa, and blueberries.

Resveratrol has been shown [in preclinical trials] to slow aging through activation of the protein deacetylase sirtuin 1 (SIRT1) gene. “Resveratrol directly binds to this enzyme, making it hyperactive. In doing so, SIRT 1 can protect the body from various toxins, damage, and inflammation,” explains Dr. Sinclair.

Dr. Sinclair also mentions that if taken in supplement form, resveratrol must be consumed with food, or something else it can dissolve in. Blood levels of resveratrol must be in the micromolar range to activate the sirtuin enzymes.

Is it possible to participate in endurance events while also pursuing longevity?

“Yes, if you get it right, you are likely to live longer and healthier than someone who doesn't do both of those things,” Dr. Sinclair responds.

It is not easy, however, to do both. Because, you are putting your body into a state of perceived adversity. He further discusses the importance of knowing your body on a deeper level through biomarker tracking. “The more you measure biomarkers and get to know your body, the more you can optimize your longevity strategy,” he says.

What is the relationship between metformin and exercise?

Dr. Sinclair explains that taking metformin at the same time you want to train will leave you feeling a bit weaker – which is why your muscles don’t bulk up as much if you take metformin with exercise.

Dr. Sinclair has tweaked his routine through data tracking and understanding of his own body. He transitions between taking metformin and exercising, – he does not work out every day or take metformin daily.

Since writing Lifespan, have you found new longevity insights that will be featured in your next book? 

Dr. Sinclair responds that in his book Lifespan, he didn’t fully appreciate the impact of diet on longevity. He has been able to further improve his biomarkers through changing his diet—specifically by not eating meat and minimizing dairy.

With this said, Lifespan is still very relevant, and the science behind it stands. “Lifespan is essentially a textbook for longevity, and is the basis of what I do as well as what you do at InsideTracker.”

Since Lifespan, Dr. Sinclair has also published his epigenetic reprogramming work. While writing Lifespan, he was still researching epigenetic reprogramming and the information theory of aging. Since publishing in Nature Magazine in 2020, the information theory of aging continues to grow in understanding and popularity.

What is the future of epigenetic reprogramming?

Dr. Sinclair’s team is investigating the next generation of drugs. They are in the process of developing medications to cure blindness through gene therapy, as mentioned in Lifespan.

Dr. Sinclair is also working on medications to reverse aging. “This would be the ultimate dream,” he says, “to take pills for a few weeks and go back decades in time.”

What’s the relationship between metformin and homocysteine levels?

With metformin, you can see a rise in homocysteine levels and you don’t want homocysteine to rise for several reasons. Increased homocysteine levels have been associated with heart disease, and can hinder DNA methylation and methylation in general, which is partly what drives the aging process, says Dr. Sinclair. He also cautions that if you take metformin, you should monitor your homocysteine levels to make sure they don’t get too high.

What’s next for Dr. Sinclair? 

Dr. Sinclair always has a full plate of researching, teaching, and lecturing in various capacities. He is also in the process of writing his second book, which should hopefully debut next year. And he is looking forward to season two of his wildly successful podcast that’s aptly named Lifespan.