Hormonal and Metabolic Changes of Aging and the Influence of Lifestyle Modifications

Abstract

Increased life expectancy combined with the aging baby boomer generation has resulted in an unprecedented global expansion of the elderly population. The growing population of older adults and increased rate of age-related chronic illness has caused a substantial socioeconomic burden. The gradual and progressive age-related decline in hormone production and action has a detrimental impact on human health by increasing risk for chronic disease and reducing life span. This article reviews the age-related decline in hormone production, as well as age-related biochemical and body composition changes that reduce the bioavailability and actions of some hormones. The impact of hormonal changes on various chronic conditions including frailty, diabetes, cardiovascular disease, and dementia are also discussed. Hormone replacement therapy has been attempted in many clinical trials to reverse and/or prevent the hormonal decline in aging to combat the progression of age-related diseases. Unfortunately, hormone replacement therapy is not a panacea, as it often results in various adverse events that outweigh its potential health benefits. Therefore, except in some specific individual cases, hormone replacement is not recommended. Rather, positive lifestyle modifications such as regular aerobic and resistance exercise programs and/or healthy calorically restricted diet can favorably affect endocrine and metabolic functions and act as countermeasures to various age-related diseases. We provide a critical review of the available data and offer recommendations that hopefully will form the groundwork for physicians/scientists to develop and optimize new endocrine-targeted therapies and lifestyle modifications that can better address age-related decline in heath.

Figure 1:. Decline in hormone production with age.

A: There is a gradual and consistent decline in T production with each year of age in men beginning around the 3^rd decade. Free T, the most biologically active form of T, declines at nearly twice the rate of total T. B: Plasma levels of DHEA and DHEA-S sharply decline at birth until the age of ~6-7. A sharp rise in the levels of DHEA and DHEA-S occurs until approximately the 3^rd decade. DHEA and DHEA-S then gradually decline until death in men and women, with a slightly steeper decline in DHEA-S compared to DHEA. C: IGF-1 consistently decreases with age beginning around the 3^rd decade in men and women. Pulsatile release of GH throughout the day maintains plasma IGF-1 levels through production and secretion from the liver. ^aT = testosterone; DHEA = dehydroepiandrosterone; DHEA-S = dehydroepiandrosterone sulfate; IGF-1 = insulin-like growth factor 1; GH = growth hormone.

Figure 2:. Schematic diagram of the aging-related influence on metabolism.

Aging results in a decline in anabolic hormone production and, as is true for a large sum of the older population, a habitual decline in physical activity. This decrease in physical activity results in lower daily energy expenditure, leading to increased rates of obesity in the older population. Moreover, both hormonal dysregulation and reduced physical activity influence the reduction in muscle mass that occurs with age, also known as sarcopenia. The increased rates of obesity in aging combined with the development of sarcopenia can have devastating consequences on metabolism. After the development of insulin resistance, obesity and sarcopenia can result in an increased risk for type 2 diabetes, hypertension, and hyperlipidemia. These metabolic disturbances are known to lead to the development of cardiovascular disease and dementia. Importantly, positive lifestyle modifications such as regular exercise and healthy diet can combat multiple nodes in this process and are critical for healthy aging and the prevention of metabolic disease.