Growth hormone treatments (and other hormone therapies) have a legitimate use in patients suffering excessively low hormone levels due to one or another cause. They have also long been overhyped and aggressively marketed by the anti-aging medicine community, not a field noted for its adherence to standards of truth and scientific accuracy. At the same time, the scientific evidence has consistently shown that aging is accelerated by higher levels of growth hormone. Tall people exhibit a modestly greater degree of age-related disease and mortality, for example, while the longest-lived mice are those with genetically engineered disruption of growth hormone function.
So what to make of this? There are obviously differences in the manifestations of aging in mice and humans, going beyond the obvious divergence in life span, despite the fact that the root causes are the same forms of cell and tissue damage in both species. The damage can be of a similar class, but different in detail, such as the identity of cross-links that cause loss of tissue elasticity. The important cross-linking molecules in mice and humans are quite different, but both contribute to stiffening of arteries and hypertension. The systems that react to damage or are made dysfunctional by it are different enough to react in different ways: mice have a far more plastic life span, capable of larger relative increases in longevity in response to improved cell maintenance or environmental factors such as calorie intake. A calorie restricted mouse and a calorie restricted human exhibit broadly similar short-term metabolic changes, but only the mouse lives 40% longer.
In an earlier article, we presented the evidence that growth hormone (GH) has an important role in the control of aging and longevity. Much of the evidence for this role of GH was derived from studies of mice with spontaneous or experimentally induced mutations affecting the somatotropic axis and transgenic mice with chronic increase in circulating GH levels. Results of these studies indicated that (i) major elevation of GH levels accelerates aging and shortens life; (ii) stimulatory actions of normal (physiological) GH levels on growth, maturation, and fecundity involve costs in terms of the rate of aging and average as well as maximal longevity; and (iii) suppression of GH signaling slows the process of aging, increases healthspan, and remarkably extends longevity at the expense of reduced growth, delayed puberty, diminutive adult body size, and reduced fecundity. Importantly, these effects of GH on aging as well as the associated trade-offs were shown to apply to normal mice (animals without genetic modifications) and to other mammalian species.
In humans, familial longevity is associated with reduced GH secretion, and height, a strongly GH-dependent trait, is negatively correlated with longevity in many (although not all) of the examined populations. Hereditary conditions of isolated GH deficiency (IGHD) or GH resistance do not extend human longevity, but appear to extend healthspan and provide strong, and in some cases complete, protection from age-associated diseases. Pathological elevation of GH levels in the syndrome of acromegaly reduces both healthspan and life expectancy, likely reflecting acceleration of the aging process.
Paradoxically, recombinant GH treatment of middle aged or elderly subjects, in whom secretion of GH is naturally reduced, can have beneficial effects on body composition along with subjective improvement in various aspects of the quality of life. Beneficial effects of insulin-like growth factor I (IGF-I), a key mediator of GH actions on various aging-associated traits, support the notion that GH can act as an anti-aging agent. However, age is not among the approved indications for GH therapy and side effects and risks of GH therapy are generally believed to outweigh known or hoped-for benefits.
Available evidence indicates that most of the aging-related effects of GH which were discovered in laboratory mice apply to other mammals, including humans, but important species differences also exist. We speculate that differences in the impact of GH on longevity in mice versus people stem from major differences in life history, energy partitioning, and reproductive strategy between species with a different pace-of-life. The slow pace-of-life of humans combined with the impacts of social organization, public health measures, and medical advances, favors longevity and makes it difficult to induce further increase in lifespan.