In 2023 a group of researchers used a genetic based research technique, Mendelian randomisation, to identify modifiable lifestyle risk factors that relate specifically to longevity. While the findings may not be surprising, they serve as a reminder to us on where we can specifically focus our efforts to reduce risk and promote longevity.
As ever, please talk to your doctor or medical practitioner most familiar with your medical history before implementing any changes in diet, exercise or lifestyle; especially if you are under treatment. We provide links to relevant studies at bottom of page.
How does Mendelian Randomisation Work?
Imagine researchers want to know if high levels of cholesterol cause heart disease, or if it's just an associated factor (a correlation). Conducting a long-term randomized controlled trial (RCT) to manipulate cholesterol levels might be expensive, time-consuming, or even unethical.
Instead, they use Mendelian randomization (MR):
Genetic Proxy for Cholesterol: Certain genetic variants are known to naturally lead to higher or lower levels of cholesterol throughout life. These variants are used as a stand-in (or "instrumental variable") for cholesterol levels.
Analysis: Researchers study people with these genetic variants to see if they are more likely to develop heart disease, independent of other lifestyle factors.
Finding: If people with genetic variants for higher cholesterol consistently show higher rates of heart disease, it provides strong evidence that high cholesterol is a causal factor in heart disease, not just a coincidence.
This method works because the genetic variants are randomly assigned at conception and are not influenced by lifestyle or environmental confounders, making the results more reliable for causal inference.
What Does the Study Show?
In the study (Ni et al), researchers examined how certain health factors relate to living up to the 90th and 99th percentiles of life expectancy. Out of the 46 factors they looked at, 9 were strongly linked to a longer life. Here's what they found:
Higher levels of HDL (good) cholesterol were associated with better odds of living longer. Why is this important? Read here.
Lower odds of living longer were found in people with the following traits:
higher body size at age 10
higher body mass index
obesity
higher diastolic blood pressure
higher systolic blood pressure
type 2 diabetes
high LDL (bad) cholesterol
high total cholesterol.
Other factors:
Starting to smoke later in life seemed to slightly improve the odds of living longer, but this was not a strong link. No, this does not mean to start smoking.
Higher educational attainment, a low genetic risk for blood clots and lower genetically predicted triglyceride levels were linked to a higher chance of living longer, but only up to the 90th percentile, not necessarily the longest lifespan: 99th percentile.
Why does BMI Matter?
An association between BMI and mortality is often made. Despite some criticism of the value of BMI on an individual basis, across a population the effects are clear. In a study looking at the BMI and mortality of 3.6 million UK residents, this is what was found:
The study showed that higher BMI is linked to a greater risk of death, especially from heart disease, more in men than in women. For both men and women, this link between BMI and risk of death became weaker in older age groups. In a closer look at the data, it is seen that the BMI with the lowest risk of death is about 23 for people under 70 years old, and about 25 for people 70 and older. Followers of longevity guru Bryan Johnson will note that, at time of writing, his BMI is an "optimal" 22.8.
In Singapore, with its mixed Chinese, Malay and South Asian population, the BMI for a normal (healthy) weight is set by the government’s Health Promotion Board at BMI 18.5 to 22.9 - lower than the healthy weight range for Caucasian populations.
What to Make of the Data?
A high body mass index and related chronic illnesses - high blood pressure, high cholesterol - are modifiable factors of ill health. These are factors that we can, with the right tools, control.
Certainly following the standard recommendations on diet, exercise, sleep will provide most benefit for most people. As will reducing stress and improving work-life balance. With those foundations in place, there is room to explore and make progress with more advanced longevity techniques, to gain advantage in the margins of health.
If you could address one area of your health, what would you start with and why?
For most people, improving health is about finding motivation and prioritising self-care with an ultimate goal of taking action. If you want to take effective and targeted steps that fit into your unique lifestyle, The Whole Health Practice is here to help.
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Stay Healthy,
Alastair
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Related Studies
The studies in the artcile above:
Ni X, Su H, Lv Y, Li R, Liu L, Zhu Y, Yang Z, Hu C. Modifiable pathways for longevity: A Mendelian randomization analysis. Clin Nutr. 2023 Jun;42(6):1041-1047. doi: 10.1016/j.clnu.2023.04.026. Epub 2023 May 5. PMID: 37172463.
Bhaskaran K, Dos-Santos-Silva I, Leon DA, Douglas IJ, Smeeth L. Association of BMI with overall and cause-specific mortality: a population-based cohort study of 3·6 million adults in the UK. Lancet Diabetes Endocrinol. 2018 Dec;6(12):944-953. doi: 10.1016/S2213-8587(18)30288-2. Epub 2018 Oct 30. PMID: 30389323; PMCID: PMC6249991.
Other:
Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement. JAMA. 2021;326(16):1614–1621. doi:10.1001/jama.2021.18236
Bowden J, Holmes MV. Meta-analysis and Mendelian randomization: A review. Res Synth Methods. 2019 Dec;10(4):486-496. doi: 10.1002/jrsm.1346. Epub 2019 Apr 23. PMID: 30861319; PMCID: PMC6973275.
Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians. BMJ. 2018 Jul 12;362:k601. doi: 10.1136/bmj.k601. PMID: 30002074; PMCID: PMC6041728.
Fontana L, Hu FB. Optimal body weight for health and longevity: bridging basic, clinical, and population research. Aging Cell. 2014 Jun;13(3):391-400. doi: 10.1111/acel.12207. Epub 2014 Mar 14. PMID: 24628815; PMCID: PMC4032609.
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