Modification of age-related immune decline in mice dietarily restricted from or after midadulthood.

Abstract

Although weaning-initiated dietary restriction of rodents is known to increase maximum survivorship and inhibit spontaneous late-life disease and immunologic aging, restriction begun in adulthood has been much less thoroughly evaluated. In the present studies, male mice ofa long-lived F1 (4)(5)(6) and is the only strategy known to slow age-related increases in mortality rates in homeotherms (7). Restriction also inhibits or delays (or both) the occurrence of many late-life diseases (8)(9)(10)(11) and retards the development of immunosenescence (12)(13)(14)(15)(16) (23) and rats (24). With regard to immunologic effects, only mouse splenocyte mitogen-induced T-cell proliferative responses (which are known to decline with age) have been looked at. These were increased in 16-to 17-mo-old mice restricted from 12 mo of age (14) and in 22-mo-old mice restricted from 17 mo of age (25).The present studies, done with male mice of the long-lived (C3H.SW/Sn X C57BL10.RIII/Sn) F1 strain (C3B10RF,),were aimed at providing further information on the impact of gradually imposed adult-initiated diet restriction on immunologic aging and spontaneous cancer incidence.MATERIALS AND METHODS Mice. C3B1ORF1 mice bred in our animal facilities were studied. Those fed Purina lab chow ad lib have a mean lifespan of ""28 mo, and those restricted at weaning have a mean lifespan of "-40 mo. Lifespan was not determined in the present experiments as all mice were killed and studied for immune parameters and cancer incidence. Stimulator cells in the cell-mediated lymphocytotoxicity (CML) study came from DBA male mice (H-2d; Jackson Laboratories).Diet Strategies. Three hundred male mice weaned at 3 to 4 wk of age were housed in groups of 4-6 with free access to Purina lab chow. At 12 mo, mice were individually caged and randomly assigned to one of two diet categories. (i) Purina 898The publication costs ofthis article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate this fact.

Dietary restriction modulates synaptic structural dynamics in the aging hippocampus

“…In conclusion, the present findings document that dietary restriction is capable of a positive modulation of the synaptic dynamic morphology which may be due to the many reported effects of a reduced caloric intake on free radical generation and/or control (4,6,7,(35)(36)(37)(38)(39)41).…”

Long-term voluntary exercise, representing habitual exercise, lowers visceral fat and alters plasma amino acid levels in mice

“…A reduction of visceral fat has also been reported in such rats [16,17]. These observations are significant in terms of our understanding of the impact of exercise; however, the observation periods (4-8 weeks), which are equivalent to 2-4 years in humans, may have been insufficient to elucidate the impact of habitual exercise [18,19]. Female A/J mice have about a 2-year mean life-span [20]; thus, 24 weeks is equivalent to one-fourth of their life-span.…”

“…We believe that the duration of voluntary exercise, 6 months, is the longest of any mouse experiments performed to date. One month for rodents may be equivalent to 2 years for humans [18,19]. The 6-month duration of the exercise period for mice in our study is equivalent to more than 10 years for humans; therefore, the duration was considered to be appropriate to evaluate the effects of exercise on biological markers.…”

“…First-strand cDNA synthesis was performed using 5 lg total RNA and the oligo-(dT) 18 primer following the manufacturer's instructions (Invitrogen). Real-time quantitative PCR was performed using SYBR Green on a TAKARA detection system (TAKARA, Shiga, Japan) under the standard conditions recommended by the manufacturer.…”

Effects of Germfree Status and Food Restriction on Longevity and Growth of Mice

“…Age-associated malignancies which contribute to early death have been correlated with decreased immune activity [7]. Weindruch et al [24,25] have suggested that immunological consequences of food restriction may contribute to of f ectson longevity and late-life spontaneous cancer. Hence, we have examined the effects of food restriction on immune system function and prolongation of life span in GF and SPF mice, yielding the following information on immunological function.…”