Senescent terminal weight loss in the male F344 rat

Abstract

. Senescent terminal weight loss in the male F344 rat. Am J Physiol Regul Integr Comp Physiol 284: R336-R342, 2003. First published October 17, 2002 10.1152/ajpregu.00640.2001.-Loss of weight, often of unknown cause and culminating in death, commonly occurs in humans at advanced ages. Rats that live to old ages, such as the Fischer 344 (F344) strain, also exhibit a terminal loss in body weight. A presently held hypothesis is that the terminal weight loss in the F344 rat model is due to reduced food intake because of an alteration in hypothalamic function resulting in early satiation. We report findings on terminal weight loss and food intake in male F344 rats fed ad libitum (AL group) or a life-prolonging dietary regimen in which caloric intake was restricted (DR group). Rats in both dietary groups that did not exhibit a terminal weight loss died at younger ages than those exhibiting the loss. Terminal weight loss in the AL group was not associated with decreased food intake; indeed, half of the rats in this group had an increased food intake during the period of terminal weight loss. This finding is not in accord with the presently held hypothesis. In the DR group, terminal weight loss was associated with reduced food intake. Pathology (renal disease and neoplasms) did not explain the presence or absence of the association between reduced food intake and weight loss in either dietary group. The duration of the period of terminal weight loss was similar for the AL and DR groups. Apparently, restricting calories delays the occurrence but does not affect the duration of senescent terminal weight loss. caloric restriction; food intake; hypothalamic function LOSS OF WEIGHT CULMINATING in death commonly occurs in humans at advanced ages and is a hallmark of a geriatric syndrome termed failure to thrive (11). Although in some individuals the loss in body weight is due to age-associated disease, the cause of this weight loss in many elderly individuals is unknown (28).Most rats that live to old ages also exhibit a terminal loss in body weight (5, 27, 33). Blanton et al. (4) proposed that the Fischer 344 (F344) rat is a good animal model for the study of the physiological basis of senescent terminal weight loss. They found the loss of weight to be associated with a decrease in food intake related to the consumption of shorter and smaller meals, rather than a decreased number of daily meals (5). These investigators hypothesized that senescent terminal weight loss is caused by neurochemical alterations in the hypothalamus resulting in dysregulation of food intake relative to the organism's energy needs (4).Since 1975, our laboratory has carried out life span studies on male F344 rats, and it was our impression that senescent weight loss often was not associated with decreased food intake. In the present study we have investigated this issue in three groups of rats studied in the 1980s and early 1990s for which detailed data are available on body weight, food intake throughout the life span, and pathological lesions at t...

Extended longevity mechanisms in short-lived progeroid mice: Identification of a preservative stress response associated with successful aging

“…Rats that live van de Ven et alto advanced age also display a related phenomenon known as senescent terminal weight loss. Although originally believed to be caused by decreased food intake, new data indicate this not to be the case (Black et al, 2003). The growth hormone/IGF-1 axis is already greatly reduced by this age, and thermoregulation and blood glucose may also be altered in this terminal senescent period (Black et al, 2003;van de Ven et al, 2006).…”

“…Although originally believed to be caused by decreased food intake, new data indicate this not to be the case (Black et al, 2003). The growth hormone/IGF-1 axis is already greatly reduced by this age, and thermoregulation and blood glucose may also be altered in this terminal senescent period (Black et al, 2003;van de Ven et al, 2006). In light of the data reviewed here, perhaps its not surprising then that rats (Black et al, 2003) (and probably mice (Miller et al, 2005)) that experience this senescent terminal weight loss "syndrome" actually live significantly longer than those that do not.…”

Stability of CART peptide expression in the nucleus accumbens in aging

“…at this age food intake declines and aging related anorexia appears in dramatic weight loss [6,20]. however, in contrast to the long period of time when strong decrease of food consumption can be seen in humans, this time period is restricted to only 3 weeks before death in rats [6,20].…”

“…in contrast to the difference in food intake, the expression of CaRt peptide was not changed in the naCC of both male and female aged rats. however, we have to emphasize that in most of the recently published studies, that have shown age-related changes of food consumption and altered of expression of peptides linked to food intake, rats between 25-30 months of age were used [2,6,15,24,25,29].…”

“…the positive energy balance of young animals supports anabolic mechanisms, but with age the catabolic processes become predominating. in middleaged rodents age-related obesity has been observed, while in old animals reduction of food intake and the loss of body weight results in a state of anorexia [6,7]. the reason for the decreased food intake is multi-factorial relating to both peripheral and central mechanisms.…”