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Influence of dietary restriction and aging on natural killer cell activity in mice
Abstract:
Natural killer cells (NK) are believed to defend against tumor growth. Because rodents subjected to dietary restriction without malnutrition live longer and develop spontaneous tumors less often or later in life than unrestricted controls, we measured NK activity in restricted and in unrestricted mice. An age-related decline in NK responses to YAC-1 tumor target cells was detected in both groups. NK responses for control mice were highest in 2- to 3-mo-old mice, sharply reduced in middle-age mice (14 to 15 mo), and slightly reduced further in old mice (30 to 33 mo). At all ages the response of restricted mice was less than that of controls. However, after injection with Poly I:C (which increases NK activity), old restricted mice showed NK cytolysis not different from young mice on either diet, and substantially higher responses than old unrestricted mice. In addition, restricted mice showed increased in vitro generation of cytotoxic T lymphocytes (CTL) to YAC-1 and P815 compared with age-matched controls. Restricted mice may better resist cancer via an NK system very responsive to induction signals coupled with a CTL system more effective than that of unrestricted controls.
Insights
Dietary restriction enhances natural killer (NK) cell activity in aged mice, improving tumor defense. This dietary intervention boosts the immune system
Area of Science:
- Immunology
- Aging Research
- Cancer Biology
Background:
- Natural killer (NK) cells are crucial for anti-tumor immunity.
- Dietary restriction (DR) without malnutrition extends lifespan and reduces tumor incidence in rodents.
- Age-related decline in NK cell activity is a known phenomenon.
Purpose of the Study:
- To investigate the impact of dietary restriction on NK cell activity in aging mice.
- To compare NK cell responses between restricted and unrestricted mice across different age groups.
- To assess the potential of dietary restriction in enhancing anti-tumor immune mechanisms.
Main Methods:
- Measurement of NK cell activity against YAC-1 tumor target cells in mice under dietary restriction and control diets.
- Administration of Poly I:C to stimulate NK cell activity.
- Assessment of in vitro generation of cytotoxic T lymphocytes (CTL) in restricted and control mice.
Main Results:
- Aged mice showed a decline in NK cell responses, evident in both dietary groups.
- Restricted mice exhibited lower baseline NK activity compared to controls at all ages.
- Poly I:C stimulation revealed that old restricted mice had NK cytolysis comparable to young mice and superior to old unrestricted mice.
- Restricted mice demonstrated increased in vitro generation of CTLs against tumor targets.
Conclusions:
- Dietary restriction may enhance cancer resistance through an NK cell system that is highly responsive to immune-boosting signals.
- The combination of a responsive NK system and a more effective CTL system in restricted mice suggests improved anti-tumor surveillance.
- Dietary restriction offers a potential strategy to bolster immune defenses against cancer in aging populations.