Exercise

1. Increase VO2 Max
VO2 max (mL/kg/min) quantifies the amount of oxygen the cardiorespiratory system can extract from inhaled air and deliver to muscles during highly intense exercise. It is the best marker of cardiorespiratory fitness we have, as it integrates multiple organs and physiological factors, primarily, stroke volume (heart), red blood cell volume (circulatory system), pulmonary diffusing capacity (lungs), capillary density (circulatory system), and mitochondrial enzyme levels (muscle)  (https://doi.org/10.1111/apha.12827, https://doi.org/10.1146/ANNUREV.PH.58.030196.000321). It has emerged as one of the strongest predictors of all-cause and disease specific mortality (https://doi.org/10.1016/j.pcad.2017.03.001). In this paper that controlled for other variables, just +1 mL/kg/min of higher VO2 max (for reference, most people are around 30) was associated with a 9% lower risk of all-cause mortality (https://pubmed.ncbi.nlm.nih.gov/27444976/). In order to increase your VO2 max, you need to engage in short and intense bursts of exercise. We know that high-intensity interval training (HIIT) elicits greater improvements in VO2 max compared to endurance or moderate-intensity training (https://doi.org/10.1249/MSS.0B013E3180304570, https://doi.org/10.1371/journal.pone.0073182, https://doi.org/10.1007/s40279-015-0365-0).

2. Majority of Aerobic Exercise at Low Intensity
VO2 max training is straining on the body and must therefore be staggered with less taxing forms of exercise. In fact, training with a greater percentage of low-intensity aerobic (another word for cardio) exercise leads to greater improvements in endurance performance (https://doi.org/10.1519/R-19725.1, https://doi.org/10.1249/01.MSS.0000155393.78744.86). Fatty acid oxidation (a fancy name for burning fat) is the predominant fuel source at exercise intensities below 65% VO2 max, but declines at higher intensities as carbohydrates and proteins are used (https://doi.org/10.1186/s12970-018-0207-1). Mitochondria, known as the powerhouse of the cell, are the structures within cells that perform this fatty acid oxidation (https://doi.org/10.1016/j.cell.2012.02.035). As a result, training at low intensity increases mitochondrial density, oxidative enzymes, and fatty acid oxidation capacity (https://doi.org/10.1055/s-2007-971921, https://doi.org/10.1113/EP085319), in other words, training mitochondria to become more efficient. Conversely, mitochondrial dysfunction, characterized by low density and poor efficiency is associated with the development of disease and has even been proposed as the mechanism by which humans age (https://doi.org/10.1016/j.molcel.2016.01.028, https://doi.org/10.3390/genes8120398).

3. Be Strong and Muscular
This one is simple. Greater muscle mass is associated with lower all-cause mortality (https://doi.org/10.1016/j.amjmed.2014.02.007), while lower amounts of muscle mass contribute to metabolic disease (https://doi.org/10.3803/EnM.2020.35.1.1). However, a growing body of evidence supports that idea that low muscle strength (not mass) is the better predictor of mortality (https://doi.org/10.1093/GERONA/61.1.72, https://doi.org/10.1093/GERONA/57.10.B359). This meta-analysis found that high grip strength was associated with a staggering 31% lower risk of death (https://doi.org/10.1016/j.apmr.2018.01.008). Resistance training has been established as the best way to increase muscle strength (https://doi.org/10.1113/EXPPHYSIOL.1989.SP003268,  https://doi.org/10.1042/BSE0440085).

4. Avoid Minor and Major Injuries At All Cost
This one is so important it gets it's own bullet point. The maximal mortality risk reduction of 35%-42% occurs in individuals who engage in 150-300 minutes of vigorous activity (running, swimming, cycling) and 300-600 minutes of moderate activity (walking, weightlifting) per week or an equivalent combination of both (https://doi.org/10.1161/CIRCULATIONAHA.121.058162). Injuries, even if themselves not serious, prevent us from reaping this benefit. The stair-step decline model of aging describes how injuries trigger periods of inactivity that causes a sharp loss of strength, coordination, or cardiovascular capacity. As we age, it becomes harder and harder, eventually impossible, to return to previous baselines after these setbacks. This makes injury prevention a non-negotiable priority. Some proactive strategies I use include: warming up and stretching before exercise, running on even and non-slippery surfaces, avoiding high-risk sports, practicing good form during resistance training, lifting responsible amounts of weight, and responding immediately to painful signals.