Notes

Humans are not naturally physically inactive, and the "sedentary death syndrome" is a significant risk factor for diseases and premature deaths. Long-lived species are more efficient in cellular maintenance, suggesting that enhancing the body's maintenance systems may slow the aging process. Interventions in poor lifestyles may prevent damage, promote repair, and increase life expectancy. About two-thirds of the major causes of death are lifestyle-related. Although a sedentary lifestyle is important in the pathogenesis of chronic diseases, little is known about the mechanisms where physical activity decreases their incidence. Future research will determine if changes in physical activity and body composition act as CR mimetics.



Physical inactivity leads to "disuse syndrome," causing premature aging, obesity, cardiovascular vulnerability, musculoskeletal fragility, and depression. This syndrome affects the young, middle-aged, and elderly, and 15% of newly diagnosed chronic diseases are due to sedentary lifestyles. Physical activity improves balance, flexibility, mental health, and overall quality of life, with lifetime benefits greater for early and consistent participation.

The 1995 guidelines for physical activity recommended at least 30 minutes of moderate intensity physical activity on most days of the week for significant health benefits. These guidelines were updated in 2007 and now require all healthy adults aged 18 to 65 years to engage in moderate-intensity aerobic physical activity for a minimum of 30 minutes on five days each week or vigorous-intensity aerobic physical activity for a minimum of 20 minutes on three days each week. The guidelines also include activities that maintain or increase flexibility and balance exercises for those at risk of falls. Recent studies have shown that exercising for 15 minutes/day has a 14% reduced risk of all-cause mortality and a 3-year longer life expectancy. Gait speed has also been associated with survival in older adults. However, at least 26% of American adults are sedentary and more than 50% are not regularly active at the minimum recommended level. The objectives of Healthy People 2010 aim to have at least 50% of American adults regularly involved in moderate to vigorous exercise.


What Does All-Cause Mortality Mean?
Definition and what it can tell you about risks to your health

All-cause mortality means death due to any cause. The term is commonly used in medical research where it is often expressed as the total number of deaths that occur within a specific timeframe and population.

For example, a 2022 report in the journal Tobacco Induced Diseases states that "smoking was associated with a significantly increased risk of all-cause mortality." In other words, smoking cigarettes increases the risk of dying prematurely due to cancer, cardiovascular disease, respiratory disease, or any other cause.1

Learning about all-cause mortality and the leading causes of death can help you make healthier choices. This article discusses the risk factors for all-cause mortality along with how to minimize your risk of certain causes.


primary prevention
Heart disease is the leading cause of death in the U.S., accounting for 33.6% of all deaths in 2007. It is the major worldwide cause of death in women, accounting for one-third of all female deaths. Primary heart disease prevention, reducing coronary heart disease risk factors in healthy people, results in a four-fold higher reduction in mortality from CHD than secondary prevention. Adherence to a healthy lifestyle is associated with a significantly lower risk of heart failure. Research shows that active conductors in London double-decker buses and postmen are protected against CHD compared to sedentary bus drivers. Exercise capacity is an important prognostic factor in people with CHD, but its effectiveness in predicting mortality is uncertain.


secondary prevention
Regular exercise and fitness can significantly reduce the risk of coronary heart disease (CHD) in patients with established CHD. Aerobic training and cardiac rehabilitation can improve quality of life for elderly women with CHD. Primary heart disease prevention reduces mortality by four times compared to secondary prevention. Adherence to a healthy lifestyle is associated with lower heart failure risk. Exercise capacity is an important prognostic factor in people with CHD, but its prediction is uncertain.

ischemic stroke
Physical activity has been shown to reduce the risk of ischemic stroke in both men and women. Studies have shown that high-fit men have a 68% lower risk of stroke mortality compared to low-fit men. Recent studies have confirmed the importance of physical activity in reducing the risk of ischemic stroke, with moderate to heavy physical activity protective against the risk in men but not women. Increased levels of physical activity are also associated with a lower risk of silent brain infarcts.

Hypertension is a growing public health issue due to cardiovascular changes in aging, including decreased elasticity and increased stiffness of coronary arteries. Lifestyle modifications, such as vigorous sports play and physical fitness, are strongly encouraged to prevent, treat, and control hypertension. Studies have shown that those who do not engage in vigorous sports play are at a 35% greater risk for hypertension. Older women may be resistant to exercise-induced reduction in systolic BP, possibly due to the lack of improvement in aortic stiffness. The American College of Sports Medicine recommends 30 or more minutes of moderate-intensity physical activity for hypertensive people on most days of the week.

Type 2 Diabetes Mellitus is a prevalent health issue in the U.S., with a significant increase in diagnosed cases since the 1950s. The disease is the seventh most common cause of death in the U.S., but its actual cause is higher due to its role in cardiovascular, cerebrovascular, and peripheral vascular diseases, hypertension, and renal disease. The major risk factors for type 2 diabetes are abdominal obesity and physical inactivity. Exercise has been shown to improve glucose metabolism, and studies have shown that lifestyle intervention can decrease the incidence of diabetes by 58% and metformin use by 31%. Studies have also shown that physical inactivity is the second most important risk factor for insulin resistance in children. In diabetic adults, walking at least two hours/week has been linked to a 39% lower all-cause mortality rate and a 34% lower cardiovascular mortality rate compared to sedentary persons.


Cancer is the second leading cause of death in the U.S., Canada, and Europe. Physical inactivity, poor nutrition, tobacco use, and poor lifestyle contribute to various cancers. Adopting an active lifestyle could reduce all-cause cancer rates by up to 46%.

prostate cancer
Physical activity and prostate cancer risk have been inconsistently studied. A literature review between 1989 and 2001 found that increased physical activity decreased the risk of prostate cancer. However, a population-based Canadian study reported mixed evidence, with only vigorous physical activity decreasing the risk. A Norwegian study found that exercise frequency and duration were inversely associated with the risk of advanced prostate cancer and cancer death. A study by Richman et al found that men who walked briskly for 3 hours/week or more had a 57% lower rate of progression than those who walked at an easy pace for less than 3 hours/week.

breast cancer
Physical activity significantly reduces the risk of breast cancer, especially in postmenopausal women. Studies show a linear decrease in breast cancer risk with increasing moderate and vigorous recreational activities. The Women's Contraceptive and Reproductive Experiences Study found that lifetime exercise activity significantly decreased breast cancer risk in all women. The Women's Health Initiative Observational Study found that strenuous physical activity three or more times/week and working up a sweat at age 35 years reduced the relative risk of breast cancer by 0.86. Obesity, which can be controlled by physical activity, is also a major risk factor for postmenopausal breast cancer.

coleteral cancer
Physical activity has a strong inverse association with the risk of colon cancer. Studies show that lifetime physical activity has a higher odds ratio for high exercisers compared to non-exercisers. Heavy occupational activity reduces the risk of distal colon cancer and rectal cancer. Increased job-related physical activity in males is associated with a significant risk reduction in both distal colon and rectal carcinoma. However, total and moderate non-job physical activity averts a positive effect on rectal cancer.

lung cancer
Physical activity has been found to have inconsistent results in relation to lung cancer risk. Studies have shown no consistent protective effect of physical activity on lung cancer risk, even after adjusting for factors like smoking, education, and diet. However, some studies have shown that physical activity can decrease the risk of lung cancer, such as the Iowa Women's Health Study and a Norwegian study. Additionally, moderate leisure-time physical activity has been found to have a lower risk of lung cancer.

ovarian cancer
Physical activity may lower the risk of ovarian cancer by decreasing circulating sex hormones, ovulation frequency, body fat, or chronic inflammation. A prospective cohort study found no overall significant association, but inverse associations were observed in various studies. Physical activity also protects against ovarian, endometrial, and postmenopausal breast cancer independently of BMI.

endometrium
Studies have shown that non-retired women with sedentary jobs or lifestyles are at a slightly increased risk of endometrial cancer. Physically inactive women are more likely to be overweight or obese. High exercise levels have been linked to a significant reduction in endometrial cancer risk. Exercise participation in both adolescence and adulthood reduces cancer risk by 40%. Reductions were also found for house-hold activities and walking for transportation.

Sarcopenia occurs when muscle mass and adaptive ability decrease due to lack of use, depletion of muscle regeneration stem cells, decline in anabolic hormones, and decreased physical activity. Muscle strength decreases by approximately 50% from 30 to 80 years, and by the seventh and eighth decades of life, maximal voluntary strength decreases by 20-40% for men and women in both proximal and distal muscles. A recent study found that moderate lifelong exercise programs can protect against harmful aging effects. Increased physical activity is associated with greater muscle mass and less truncal body fat, and progressive resistance training can lead to significant improvements in muscle strength in frail individuals.


Osteoporosis is a common issue in postmenopausal women and the elderly, causing a decrease in bone mineral density (BMD) and increased fractures. It affects 20 million Americans and another million will develop the disease unless preventive action is taken. Over 1.5 million fractures occur annually in the U.S., resulting in 500,000 hospitalizations, 800,000 emergency room visits, 2.6 million physician visits, 180,000 nursing home admissions, and 12-18 billion dollars in healthcare costs. Physical activity is an important factor in reducing or preventing osteoporosis, especially during childhood and adolescence. Studies have shown that increased physical activity during peak bone acquisition (age 12-18 years) has lasting benefits for lumbar spine and proximal femoral BMD. However, walking only has a significant positive effect on lumbar BMD, not on the femur or calcaneus.


physical disability
As individuals age, they are at a higher risk of becoming frail and disabled. Studies show that runners' club members have better overall health and less disability, with factors like medication, smoking, age, blood pressure, arthritis, and less physical activity predicting greater disability. Engaging in aerobic activities, such as running, can reduce mortality and disability development. Regular exercise can compress morbidity into later years, with runners' club membership and participation being protective against mortality.

obesity or over weight
Physical inactivity and obesity are major public health concerns in the industrialized world, contributing to all-cause and cause-specific mortality among young and middle-aged adults. Studies have shown that lean inactive women have higher mortality risks than physically active lean women. A BMI greater than 25 and less than 3.5 hours of physical activity each week account for 31% of premature deaths. Maintaining normal weight requires 60 minutes of daily moderate intensity activity. Extracurricular wheel-related activities can reduce the likelihood of being overweight young adults. The HALE project found that adherence to a Mediterranean diet, moderate alcohol use, physical activity, and non-smoking can lower the all-cause mortality rate to 0.35.

Depression is the leading cause of nonfatal medical disability in developed countries and the 10th leading cause of death in the U.S. Physical activity has been shown to delay these disorders, with studies showing that aerobic exercise, antidepressants, or combined exercise and medication can reduce depression after 15 weeks. Studies have also found that inactive elderly individuals have higher depression scores, and those who exercise regularly experience less depression, anger, and stress. treadmill walking has also shown significant improvement in those with major depressive disorders.

alzimer
Regular exercise can improve cognitive function in older adults, as it can mitigate the negative effects of aging on the hippocampus and olfactory systems of the adult brain. Studies have shown that regular exercise can improve neurogenesis and dentate gyrus cerebral blood volume, which correlates with cardiopulmonary and cognitive function in humans. Regular long-term physical activity, such as walking, can also maintain cognitive function in older adults. Studies have shown that women in the highest activity quintile have a 20% lower risk of cognitive impairment. Increased cardiovascular fitness can also improve the attentional brain network during cognitively challenging tasks. Alzheimer's disease (AD) is the sixth leading cause of death in the U.S., with factors such as age, family history, education level, and the presence of the apolipoprotein E (APOE) genotype e4. Environmental enrichment can decrease amyloid protein accumulation and alter gene expression changes in mice. Regular physical activity may reduce the risk or delay the onset of dementia and AD, especially among genetically.

Dementia/Alzheimer’s Disease
Miscellaneous Diseases/Disorders
Inflammation and Atherosclerosis

Inflammation is a widely accepted mechanism for atherosclerosis, which is the leading cause of death in the U.S. and most Western countries. Studies have shown that increased blood levels of high sensitivity C-reactive protein (hs-CRP) are a strong predictor of future CHD. Physical activity can decrease the inflammatory process, potentially retarding the process of atherosclerosis in patients with CHD.

immune system
The immune system's decline with aging can lead to increased infectious diseases, malignancy, and autoimmune disorders. Physical activity levels may influence this, as moderate exercise can attenuate immunosenescence in the elderly. However, intense long-term exercise, such as marathon running, can increase susceptibility to URTI. Regular exercise also accelerates wound healing in the elderly, with the exercise group experiencing faster wound healing rates compared to the sedentary group.

Metabolic syndrome, a combination of cardio-metabolic risk factors, is linked to leisure time sedentary behavior and cardiovascular disease risk factors. Men with four or more LTSB hours/day have a 1.94 odds of developing the syndrome, while women with high LTSB risk only have an increased risk.

summary

Physical activity clearly leads to increased physical fitness, exercise capacity, and risk reduction of a wide variety of pathological diseases and clinical disorders resulting in lower rates of morbidity, all-cause and cause-specific mortality, and increased life expectancy. More specifically, physical inactivity increases the risk of coronary heart and cerebrovascular diseases, type 2 diabetes mellitus, hypertension, several cancers (e.g., lung, prostate, breast, colon, others), osteoporosis/fractures and dementia, among others. However, even among the very old “not only continuing but also initiating” physical activity is associated with better survival and function [165]. Moreover, since there is a linear relationship between the level of physical activity and health status, children and adolescents should participate daily in 60 minutes or more of moderate to vigorous physical activity that is enjoyable, involves a variety of activities, and is developmentally beneficial.