Comparative Endocrinology of Aging and Longevity Regulation

Abstract

Hormones regulate growth, development, metabolism, and other complex processes in multicellular animals. For many years it has been suggested that hormones may also influence the rate of the aging process. Aging is a multifactorial process that causes biological systems to break down and cease to function in adult organisms as time passes, eventually leading to death. The exact underlying causes of the aging process remain a topic for debate, and clues that may shed light on these causes are eagerly sought after. In the last two decades, gene mutations that result in delayed aging and extended longevity have been discovered, and many of the affected genes have been components of endocrine signaling pathways. In this review we summarize the current knowledge on the roles of endocrine signaling in the regulation of aging and longevity in various animals. We begin by discussing the notion that conserved systems, including endocrine signaling pathways, “regulate” the aging process. Findings from the major model organisms: worms, flies, and rodents, are then outlined. Unique lessons from studies of non-traditional models: bees, salmon, and naked mole rats, are also discussed. Finally, we summarize the endocrinology of aging in humans, including changes in hormone levels with age, and the involvement of hormones in aging-related diseases. The most well studied and widely conserved endocrine pathway that affects aging is the insulin/insulin-like growth factor system. Mutations in genes of this pathway increase the lifespan of worms, flies, and mice. Population genetic evidence also suggests this pathway’s involvement in human aging. Other hormones including steroids have been linked to aging only in a subset of the models studied. Because of the value of comparative studies, it is suggested that the aging field could benefit from adoption of additional model organisms.

Insulin-Like Growth Factor Binding Protein-5 in Physiology and Disease

“…IGFBP-5 may play a role in the pathogenesis of atherosclerosis, which is a process of inflammatory tissue remodeling within the matrix of the arterial wall that is the top cause of cardiovascular disease and aging-related mortality in humans (136). A cross-sectional case-control study found a positive association between circulating IGFBP-5 levels and coronary heart disease (137).…”

“…The role of IGFBP-5 in both atherosclerosis and fibrosis may be linked to the induction of cellular senescence (145,151). Aged artery walls are more susceptible to atherosclerosis and hypertension which may be related to accumulation of senescent cells and the resultant compositional changes in the subendothelial matrix (136). The accumulation of senescent cells in the arteries of children with the premature aging disease Hutchinson-Gilford Progeria seems to be the cause of their severe accelerated atherosclerosis and premature death from resulting stroke or heart attack before age 20 (152,153).…”

“…IGFBP-5 was upregulated in senescent human umbilical vein endothelial cells and knock down of IGFBP-5 partially reversed the senescence, suggesting a role for IGFBP-5 in promoting cellular senescence (145). The accumulation of senescent cells may play a causal role in many aspects of the vertebrate aging process, which is known to be promoted by IGF signaling (136). Future research will determine the extent to which IGFBP-5 may be involved in linking IGF signaling to aging-related changes in tissues and the pathology of aging related diseases.…”

How age, sex and genotype shape the stress response

“…For instance, the use of different endpoints across studies, combined with the lack of a necropsy report, can render an aging study incomplete ( Santulli et al., 2015 , Treuting et al., 2016 ). Similarly, the use of different paradigms of chronic stress render inter-study consistency even more difficult to achieve ( Allard and Duan, 2011 ). These are some of the critical challenges for the field in the near future; hopefully, more multi-centric collaborative research efforts may allow for the overcome of such critical obstacles.…”

<p>Hormonal Function Responses to Moderate Aerobic Exercise in Older Adults with Depression</p>

“…36 During aging, the increase in the cortisol/DHEAS ratio refers significantly to an increase in the neurotoxicity and probably contributes to the occurrence of age-related neurodegenerative illnesses. 37,38 Thus, higher secretions of DHEA/DHEAS considered of great importance in improving health outcomes, [39][40][41][42] including psychological status, and reduced risk of death from cardiovascular disease. [39][40][41][42] Similarly, corticosterone (CORT) levels were generally raised following stressful events and impairs in cognition/memory and stress coping which in turn lead to a reduction in the structural and functional plasticity of the brain.…”