Effects of growth hormone and insulinlike growth factor 1 deficiency on ageing and longevity

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Zvi Laron

Endocrinology & Diabetes Research Unit, Schneider Children's Medical Center of Israel and Sackler Faculty of Medicine, Tel Aviv University, Israel

Abstract: Present knowledge on the effects of growth hormone (GH)/insulin-like growth hormone (IGF)1 deficiency on ageing and lifespan are reviewed. Evidence is presented that isolated GH deficiency (IGHD), multiple pituitary hormone deficiencies (MPHD) including GH, as well as primary IGF1 deficiency (GH resistance, Laron syndrome) present signs of early ageing such as thin and wrinkled skin, obesity, hyperglycemia and osteoporosis. These changes do not seem to affect the lifespan, as patients reach old age. Animal models of genetic MPHD (Ames and Snell mice) and GH receptor knockout mice (primary IGF1 deficiency) also have a statistically significant higher longevity compared to normal controls. On the contrary, mice transgenic for GH and acromegalic patients secreting large amounts of GH have premature death. In conclusion longstanding GH/IGF1 deficiency affects several parameters of the ageing process without impairing lifespan, and as shown in animal models prolongs longevity. In contrast high GH/IGF1 levels accelerate death.

2002 Endocrine facets of ageing. Wiley, Chichester (Novartis Foundation Symposium 242) p 125-142

In contrast to growth and development, ageing is a progressive process orchestrated by decreasing synthesis and secretion of numerous factors and hormones; among them growth hormone (GH) and its anabolic effector hormone, insulin-like growth factor 1 (IGF1). Therefore, ageing is often compared with growth hormone deficiency (GHD) (Toogood & Shalet 1998). This assumption is based on the evidence that pituitary GH secretion and serum IGF1 concentrations decline with increasing age (Gil-Ad et al 1984, Arvat et al 2000), reaching low levels in late adulthood, and have similarities to changes of body appearance, composition and function (Carroll et al 1998, Toogood & Shalet 1998) (Table 1). These findings led to trials of GH treatment in elderly people (Rudman et al 1990). The finding that GH increased lean body mass, decreased adiposity and improved apparent skin changes gave birth to an

TABLE 1 Similarities between GH deficiency and ageing

Thinning of skin (wrinkling)

Excess adipose tissue (obesity)

Rise in insulin resistance (tendency for diabetes)

Decline in b cell function

Reduced lean body (muscle) mass

Reduced physical performance

Reduced mineral density (osteoporosis)

Lowered venous access

Rise in serum cholesterol approved (Butterfield et al 1997) and non-approved administration of GH to ageing people, at 'so-called' rejuvenation clinics. These medical acts were reinforced by reports that GH deficiency increases the risk for cardiovascular disease (Rosen et al 1993) and leads to premature mortality (Rosen & Bengtsson 1990).

In order to analyse the present knowledge on the possible role of GH and IGF1 in ageing and lifespan, this paper reviews states of congenital (i.e. primary) GH and/or IGF1 deficiency in humans and animals. Attention is paid as to whether patients or animals with GH/IGF1 deficiency present early signs of ageing and effects on the duration of their lifespan.

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