IGF1 and insulin secretion during ageing

The secretion of GH decreases with advancing age, mainly through a decrease in the amplitude of GH pulses (Veldhuis et al 1995). Mean 24 h GH concentrations decline from late puberty into old age (Rudman et al 1981) due to decreased GH production and an increased clearance rate (Iranmanesh et al 1991). The changes in IGF1 levels throughout life appear to mimic those of GH (Ho et al 1987).

Accordingly, in a cross-sectional study of healthy adults with similar lean body mass (LBM), the IGF1 blood levels decreased with population age (Ruiz-Torres & Corpas 1993), independently of adiposity (Copeland et al 1990). We observed that the slope of the corresponding curve shows differences dependent on the age range considered. In the range between 20 and 50 years the slope is clearly steeper than when all age groups up to a very advanced age are included. This indicates that people with low levels of IGF1 die earlier so that the average value in the surviving group is increased. Consequently, the curve obtained up to around 50 years age (and then extrapolated) represents a more realistic behaviour of IGF1 and should be considered as a standard reference curve.

These results could help explain the role of IGF1 levels on age-related differences in, for example, testosterone, thyroid hormone and procollagen III peptide blood concentrations that disappear when comparing young and old persons with similar IGF1 values (Table 1). Furthermore, individuals of very advanced age show IGF1 blood levels clearly above the standard regression curve, the behaviour of which is not affected by the selection of individuals by mortality (Soares de Melo 1997).

In a similar defined population of healthy individuals (as mentioned earlier) insulin levels are usually increased with advancing age (Ruiz-Torres et al 1996).

TABLE 1 Differences between younga and oldb depending on IGF1 blood level in males

IGF1

Testosterone PIIIP

Young versus old

Decreased Decreased P <0.0001 P< 0.0001

Increased Decreased

Increased NS P<0.01

Lowest range in young versus NS highest in old

of IGF1

a20-39 years age, n = 22. b70—92 years age, n = 33.

LBM, lean body mass; NS, difference not significant; PIIIP, procollagen III peptide.

FIG. 1. IGF1 serum levels and insulin secretion of young (20—39 years old, n = 22) and old (70—92, n = 33) healthy men with corresponding anthropometrical manifestations. On the right are blood concentrations of the N-terminal peptide of procollagen type III (PIIIP). The figure shows the opposite age-dependent behaviour of the hormones mentioned. IGF1 concentrations were determined after alcohol extraction by radioimmunoassay and PIIIP. Daily insulin secretion was by means of 24 h C-peptide excretion, corrections and normalization of results as described (Ruiz-Torres et al 1996); LBM calculated according to Forbes & Bruining (1976); and adipose mass worked out on the basis of skin fold thickness and body density according to Durnin & Womersley (1974).

FIG. 1. IGF1 serum levels and insulin secretion of young (20—39 years old, n = 22) and old (70—92, n = 33) healthy men with corresponding anthropometrical manifestations. On the right are blood concentrations of the N-terminal peptide of procollagen type III (PIIIP). The figure shows the opposite age-dependent behaviour of the hormones mentioned. IGF1 concentrations were determined after alcohol extraction by radioimmunoassay and PIIIP. Daily insulin secretion was by means of 24 h C-peptide excretion, corrections and normalization of results as described (Ruiz-Torres et al 1996); LBM calculated according to Forbes & Bruining (1976); and adipose mass worked out on the basis of skin fold thickness and body density according to Durnin & Womersley (1974).

This elevation of insulin is related to the increased body fat mass and reduced muscle mass, the latter primarily due to the progressive decrease of GH/IGF1 secretion (Fig. 1). Moreover, the reverse correlation between insulin secretion and IGF1 blood levels could be understood as a wear and tear effect. Nevertheless, it needs to be stressed that all regulatory processes have some side effects, in this case those concerning excessive amounts of insulin with or without hyperinsulinaemia.

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