Insights

There have been countless proposals over the years for ways in which to beat ageing, with some proposers arguing that following their diets, exercise or other plans will enable you to grow to a ripe old age, remaining fit and healthy along the way.

In the modern age, the old “Snake Oil Salesmen” of yesteryear have been replaced by influencers who rely on social media to promote their ideas.  Unlike the Snake Oil Salesmen who typically sold elixirs containing innocuous ingredients or sometimes even toxic substances as a “cure all”, many of today’s longevity promoters base their ideas on actual scientific evidence.

The term “biohacking” refers to non-specific lifestyle self-improvement by making changes to one’s, diet, exercise and lifestyle to improve one’s body, health and overall well-being.

Bryan Johnson is one of many influencers who attempts to beat ageing and maintain excellent health through a regimen of vitamins and other supplements and wellness activities.

In this article, we’ll explore some of the activities and interventions that Bryan Johsnon and others use, and explain the scientific reasoning behind them, including the pros and cons related to each.

Bryan Johnson and “Project Blueprint” — a quick overview

Bryan Johnson is a tech entrepreneur who follows an extreme and intensive health program that he publishes online.  He has named his program “Project Blueprint” and it combines strict diets and calorie control with the consumption of dozens of supplements and targeted prescription medicines and lifestyle practices such as sleep optimisation, sauna/cold exposure and exercise.  Along with all of this, he undertakes continuous monitoring and regular advanced testing, including MRIs, organ screens and measurement of blood biomarkers.

His extreme methods have raised comment for both his results and the medical/ethical questions that his approach raises.

Many of the individual practices that Bryan Johnson is following have been tried in one form or another by many others.  We’ll look at each of them.

1) Calorie restriction / very low-body-fat diet

In Bryan’s case, he follows a very tightly controlled calorie intake and dietary composition with the aim of achieving biological markers that resemble younger adults.

Studies have shown that calories restriction extends lifespan in many animals species.  A study in humans demonstrated that calorie restriction of approximately 25% over a period of 2 years did result in improved cardiometabolic risk markers and reduced some markers of ageing physiology.[i]  This study showed that participants had an improvement in their insulin sensitivity index, a decrease in blood pressure and improvement in many cardiometabolic risk factors.

Similar studies have demonstrated decreases in cardiometabolic risk factors.[ii]

The problems with calorie restriction however relate to the difficulties in maintaining it over long periods, along with low energy levels, reduced libido, low body fat and nutritional insufficiencies if not medically supervised.  It is also unknown if there is a long-term extension of life span or if there are long-term issues related to bone and/or muscle loss.

2)  Time-restricted eating / intermittent fasting

Another tool used by Bryan Johnson and many others is intermittent fasting or time-restricted eating whereby eating is restricted to particular hours within a day.

A randomised, controlled study by Sutton et al. (2018) demonstrated that restricting eating to earlier in the day only had metabolic benefits including improved insulin sensitivity, blood pressure and oxidative stress markers, even in the absence of weight loss.[iii]

The evidence for the long-term benefits associated with intermittent fasting or time-restricted eating is however, not uniformly conclusive, with other studies showing only small or no effects.[iv]

3)  NAD+ precursors (NR, NMN) and related “cell-energy” supplements

Nicotinamide adenine dinucleotide (NAD+) precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are supplements that can influence the level of NAD+, which is an essential element found in all living cells playing a critical role in metabolism, energy production and cellular repair.

Studies in animals have shown that boosting NAD+ improves mitochondrial function and some age-related phenotypes.  Studies in humans have shown that NR and NMN raise NAD+ metabolites, but, whilst plausible, clinical benefits related to ageing endpoints are not clear.[v]^,[vi]

4) Prescription drugs repurposed for “anti-ageing” (e.g., metformin, rapamycin/rapalogs, acarbose, others)

Metformin is a prescription medicine that is used to treat high blood sugar levels in patients with Type 2 diabetes.  It works by reducing the amount of glucose in the blood through reducing the absorption of glucose from food that is eaten and also from glucose that is made naturally by the liver.  It also increases the body’s response to insulin.

Rapamycin, and its analogues (known as rapalogs) are also a prescription medicine, and is used to coat coronary stents to prevent narrowing of blood vessels, and also to prevent organ transplant rejection through some immunosuppressant functions, among some other uses.  Some early human studies have suggested that rapamycin and related drugs may have clinically beneficial effects on immune and age-related measures, but can also cause adverse effects.[vii]

Whilst these drugs can be useful and beneficial for patients with the conditions for which they are normally prescribed, their use as a means to longevity is not generally recommended due to the potential for serious side effects in otherwise healthy individuals.

Indeed, Bryan Johsnon, as part of his protocol, has included prescription agents, but , despite careful biomarker monitoring and medical oversight, experienced adverse effects and publicly reported stopping at least one experimental drug.

5) Senolytics (dasatinib + quercetin, fisetin, etc.)

Senolytics are a class of drugs that selectively target and eliminate senescent cells.  Whilst some are available as prescription medicines, most are still undergoing research and development and are thus not available.

Some biohackers use senolytic drugs periodically to clear senescent cells.

The results from some early stage human clinical studies suggest that senolytics may alleviate physical dysfunction in idiopathic pulmonary fibrosis, which is age-related, chronic, irreversible fibrotic lung disease.[viii]^,[ix]  The safety and efficacy for broad use of these drugs is, however, unproven.

6) Advanced monitoring and frequent medical testing

Advanced monitoring and medical testing can indeed detect treatable conditions earlier, but more testing can lead to incidental findings and cause unnecessary anxiety.  There is also a significant cost involved in frequent testing, especially in the absence of symptoms or other indicators to support additional testing.

There is little evidence to support acting on small biomarker shifts that may occur with high frequency testing in order to improve long-term outcomes.

7) Exercise, resistance training, sleep optimization

There are significant bodies of scientific evidence to support exercise, and especially resistance training, to preserve muscle mass, strength and metabolic health, and thus reduce the frailty that can occur with ageing and generally improve multiple health outcomes.

Equally, sleep quality has been shown to be strongly linked to cardiometabolic and cognitive health.

These strategies are widely prescribed for the majority of people as well established, low-risk activities to improve lifespan.

8) Sauna / heat therapy and cold exposure

Sauna bathing has been linked to lower cardiovascular and all-cause mortality events.[x]

Cold exposure through cryotherapy and other means is similarly linked to short-term metabolic or recovery benefits, but long-term anti-ageing data is scarce.

It should be noted that heat/cold therapies can be risky in people with cardiovascular instability, and especially if people are not accustomed to this type of therapy.

9) High-volume supplement stacks

Some supplements, such as omega 3-fatty acids, vitamin D, iron or vitamin B12, when deficient, have good evidence for the correction of deficiencies.  Clinical trials of other single supplements show mixed results, with some supplements showing harm when given in high doses.

Supplement stacks, when a number of different supplements are taken together, have few clinical studies to support their use, and clinical benefits for overall longevity are unproven.

As widely prescribed, a healthy, balanced diet will, in most cases, provide the vitamins, minerals, antioxidants and other requirements for healthy living.

Practical takeaways / recommendations (evidence-based, risk-sensible)

For most healthy people, a balanced diet, exercise – both resistance and aerobic – and high quality sleep are the factors with the strongest scientific evidence for a healthy life.  Monitoring, and where necessary, controlling, key physiological parameters such as blood pressure, lipids and diabetes, along with maintaining a healthy body composition are also important.

If considering drugs or novel supplements, this must be done under the supervision of specialist clinicians as there can be adverse effects and unknown long-term risks.

Interpretation of short-term biomarker improvements can be misleading as these changes don’t necessarily provide proof of increased longevity.

Bottom Line

So, in short, the bottom line for these interventions in terms of increasing longevity is as follows:

• Strongest evidence:  exercise, good sleep, healthy diet and smoking cessation/alcohol moderation.
• Encouraging but not proven:  calorie restriction, time-restricted eating, sauna and rapalogs in small trials.
• Promising but preliminary:  NAD+ boosters and senolytics.
• Riskier : polypharmacy supplement/drug stacks without trials.

[i]     Kraus, W.E., Bhapkar, M Huffman, K.M., Pieper, C.F., Das, S.K. and Redman, L.M. (2019). 2 years of calorie restriction and cardiometabolic reis (CALERIE):  exploratory outcomes of a multicentre, phase 2, randomised controlled trial.  Lancet, 7(9), pp 673-683.

[ii]     Ravussin, E., Redman, L.M., Rochon, J. et al. (2015).  A 2-year randomised controlled trial of human caloric restriction:  feasibility and effects on predictors of health span and longevity.  J. Gerontol., 70(9), pp 1097-1104.

[iii]    Sutton, E.F., Beyl, R, Early, K.S., Cefalu, W.T., Ravussin, E and Peterson, C.M. (2018).  Early time-restricted feeding improves insulin sensitivity, blood pressure, and oxidative stress eve without weight loss in men with prediabetes.  Cell Metab., 27(6), pp 1212-1221.

[iv]    Liu, J., Yi, P. and Liu, F. (2023).  The effect of early time-restricted eating vs later time-restricted eating on weight loss and metabolic health.  J. Clin. Endocrin. Metab., 108(7), pp 1824-1834.

[v]     Reiten, O.K., Wilvang, M.A., Mitchell, S.J., Hu, Z. And Fang, E.F. (2021).  Preclinical and clinical evidence of NAD+ precursors in health, disease, and ageing.  Mech. Ageing Dev., 199, article 111567.

[vi]    Freeberg, K.A., Udovich, C.C., Martens, C.R., Seals, D.R. and Craighead, D.H.  (2023).  Dietary supplements with NAD+-boosting compounds in humans:  current knowledge and future directions.  J. Gerontol., 78(12), pp 2435-2448.

[vii]   Mannick, J.B., Morris, M., Hockey, H.-U.P., et al. (2018).  TORC1 inhibition enhances immune function and reduces infections in the elderly.  Science Trans. Med., 10(449), eaaq1564.

[viii]   Nambiar, A., Kellog III, D., Justic, J., et al. (2023).  Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis:  results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability.  eBioMed., 90, 104481.

[ix]    Justice, J.N., Nambiar, A.M., Tchkonia, T., et al. (2019).  Senolytics in idiopathic pulmonary fibrosis:  results from a firs-in-human, open-label, pilot study.  eBioMed., 40, pp554-563.

[x]     Laukkanen, T., Khan, H., Zaccardi, F., et al. (2015).  Association between sauna bathing and fatal cardiovascular and all-cause mortality events.  JAMA Int. Med., 175(4), pp 542-548.