Metabolic Disequilibrium and Aging: Modifying
Favorably with Calorie Restriction and Calorie Restriction Mimetics by Vinod
Nikhra* in Gerontology & Geriatrics Studies _ International Journal of
Gerontology
Abstract
Metabolic
disease and aging: There are increasing
evidence that metabolic disequilibrium and disorders influence the aging
process and survival including the quality of life (QOL). The adipose tissue
mediates various age-associated metabolic disorders such as insulin resistance
(IR), metabolic syndrome (MetS), dyslipidemia and type 2 diabetes mellitus (T2DM),
altogether which can negatively affect the lifespan and sends signals to modify
the aging process in various tissues and organs. The role of master-switch and
genomic guardian, p53 is important in this context.
Calorie
restriction (Cr): The energy needs are
determined by the body composition, especially the fat free lean mass and level
of physical activity, and there is a change in nutritional needs during the
middle age and later. The diet-gene interaction is a major determinant of
health and illness, and the amount and type of food ingestion and caloric
intake, in general, influence the health and life span. An excess calorie
intake causes overnutrition and nutritional overload leading to increased
adipose stores culminating as weight gain and obesity, which lead to IR, MetS, T2DM and other metabolic
alterations. At the subcellular and cellular level there is increased
potentially damaging exposure to reactive oxygen species (ROS).
Cr Mechanisms
and pathways: There have been
identified several metabolic and genetic pathways that govern food ingestion,
metabolism and life span. Experimentally, the CR has been shown to achieve
increased lifespan in a broad spectrum of life forms from yeast, nematode,
fruit fly, rodents and primates, including Homo sapiens, endosing that a diet
adequately fulfilling nutritional needs, but low in calories may improve
health, prevent many late-onset diseases and extend the life span. But, the
benefits of CR are not a passive result of lower caloric intake but the
consequence of an active regulatory intervention mimicking the food scarcity
and activating certain genetic and metabolic programs that result in various
vital beneficial effects. The genetic and molecular studies in model organisms,
in fact, suggest that CR is a regulated process, in which the SIRT (Silent
Information Regulator 2) gene plays an important role.
Impact of Cr On
Qol and disease: CR has long been
recognized for its ability to extend life span and mitigate aging and stall
disease processes in various organs. The data from animal and human studies
indicate that the CR affects favorably several metabolic and molecular factors
that modulate cardiovascular age-related alterations including cardiac and
arterial stiffness, hypertension and heart rate variability. These effects, in
combination with various other benefits, such as protection against adiposity,
IR and T2DM, neurodegenerative diseases and cancer, suggest that the CR may
have a major beneficial effect on health status, quality of life and life span
in humans.
Keywords: Calorie restriction; Cardiovascular disease; Metabolic syndrome;
Neuro-degenerative disorders p53; Reactive oxygen species; SIRT gene; Type 2
diabetes mellitus
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