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Giambattista Salinari and Gustavo De Santis

60% of the ad libitum condition) and calorie restriction was somewhere in between. Figure
5 showed that the relationship between caloric intake and survival was not linear. In star-
vation, an increase in nutrition enhances the likelihood of survival, which is also true in
humans (Woodward, 1998). What was probably surprising was that survival peaked under
severe caloric restriction, at about 50% of the ad libitum intake and started to decline
beyond this threshold.
Upon closer inspection of the settings and results of the CR experiments, focusing only
on rodents, the following points deserved attention:
1. Experiments on rodents are generally carried out in a pathogen-free environment.
The presence of pathogens may alter the connection between nutrition and survival.
2. A long-term 30-60% reduction in calorie intake below ad libitum feeding causes an
increase in maximum life ranging between 30-60% if calorie restriction starts just
after weaning and 10-20% if CR starts in adulthood instead (Omodei and Fontana,
2011).
3. Much of the improvements registered in the mean and maximum life span derived
from a retardation in the age-dependent increase in mortality (Weindruch and Wal-
ford, 1982; Harper, Leathers and Austad 2006) and from a lower rate of ageing
usually measured by OLS estimates of a Gompertz model (Masoro, 2005).
4. In CR rodents, several age-related diseases appear later in life and are less lethal.
This holds true for cancer, cardiovascular diseases, stroke, kidney failure, diabetes,
Alzheimer, Parkinson and Huntington’s disease (Omodei and Fontana, 2011).
5. CR rodents show lower levels of a few well-known biomarkers of ageing among
which are reactive oxygen species (ROS) and pro-inflammatory cytokines (Omodei
and Fontana, 2011).
Two main conclusions emerged. First, CR has long lasting effects (point 2). Secondly,
most of the evidence on the effects of caloric restriction points to ageing rates (the β pa-
rameter) rather than to the initial level of mortality (the α parameter), points 3–5.
These CR experiments seem to contradict a large body of evidence from historical de-
mography (Bengtsson, 2004), epidemiology (Waaler, 1984), economic history (Fogel &
Costa, 1997; Fogel, 2004) and biology (Bateson et al., 2004), which suggested that better
nutrition is associated with higher survival in humans. The central point is probably
represented by the fact that CR experiments are carried out in a pathogen-free setting
(point 1) which is clearly not the case for historic populations. A relatively recent line of
research has investigated the characteristics of the immune system of CR rodents and its
capacity to respond to infectious pathogens. The results have been mixed. On one hand,
CR apparently attenuates age-related decline in the immune system of rodents (delayed
immune-senescence) (Kristan, 2008; Pahlavani, 2004). On the other, studies using bacteria
(Sun, Muthukumar, Lawrence et al., 2001), viruses (Gardner, 2005; Ritz and Gardner,
2006; Ritz, Aktan, Nogusa et al., 2008) and parasites (Kristan 2007) showed a significant-
ly reduced capacity of long-term CR rodents to respond to and to survive such infections
despite their better immune system. This happened because the response of the immune
system to an infectious pathogen is very expensive in terms of energy and the body of CR
rodents may fail to mobilize the energy needed (Ritz and Gardner, 2006).
In Figure 6 we summed things up. In a pathogen-free environment, a reduced caloric
intake apparently retards ageing and slows it down (Figure 6(A)). However, with patho-
gens, a reduced caloric intake produces an upward shift of the mortality hazard function as
a consequence of the difficulties of the immune system in mobilizing the energies the body
needs to fight infections and heal wounds (Figure 6(B)).
Results presented in Figures 2 to 4 were essentially consistent with the outcomes of the

International Journal of Population Studies | 2015, Volume 1, Issue 1 51