Caloric restriction and the phytoalexin resveratrol found to increase longevity and decrease aging. This is the summary I have made after extensive review. everybody is invited to comment on it.

1. Addis Ababa University
School of Medicine
Department of Biochemistry
Integrated Metabolism Seminar
Title : Resveratrol, Caloric Restriction and Longevity in Human Mitochondrial Dysfunction
SUMMARY
Aging is a complex process involving a multitudes of factors. Even though multiple theories are available
to explain the causes of aging, the oxidative stress and mitochondrial dysfunction are found to be the
important factorscontributing to the aging process. Indeed, damage to mitochondrial DNA might lead to
mitochondrial dysfunction and hence in oxidative phosphorylation and ATP synthesis. Heterogeneous
class of disorders always linked to mitochondrial defect and oxidative stressresulting the pathogenesis of
age-associated neurodegenerative and metabolic diseases such as Alzheimer's disease, Parkinson's
disease, and Huntington's disease,cancer, diabetes mellitus and etc. The growing evidence is showing
that the possibility slowing down or reversing the processes of aging to extend both the maximum and
average lifespan. The NAD+
-dependent protein deacetylases called sirtuins are found to be important
regulators of organisms life span. Caloric restriction and resveratrol are found to activates sirtuins and
prolongs aging. Experimental and theoretical consensus supports in semi starvation mode activate
pathway that reduce cellular damage and improve metabolic efficiency. Indeed, caloric restriction
activate AMPK and resulting up-regulation of NAMPT the rate limiting enzyme for NAD denovo
biosynthesis leading higherNAD+ levels and SIRT1 activity. SIRT1 bind to PPARγ which is a nuclear
hormone receptor that activates transcription of genes involved in adipogenesis and fat storage a nd
repressestranscription of these genes,leading to loss of fat store. Since the concentration of adiponectin
increases during caloric restriction influx of calcium ion increases in myocytes resulting activation
AMPK through phoshorylation of CaMKKβ. The CaMKKβ-mediated activation of AMPK increased
SIRT1-mediated deacetylation of PGC-1α and increase mitochondrial biogenesis. Activation of SIRT1
affectsvarious genes in our tissue which repress many age related diseases. Resveratrol is naturally
produced antioxidant by plants as a defense systemagainst infection and oxidative stress due to external
attacks. Reseveratrol inducesapoptosis in unhealthy cells, promotesnormal nuclear factor kappa B and
cyclooxygenase-2 activity, promotes normal activity of the SIRT-1 gene (involved in calorie restriction,
fat mobilization, mitochondrial function, longevity), promotes cardiovascular health, possibly fights
obesity and diabetes.Activation of SIRT1 though caloric restriction and resveratrol leading to increased
physical activity, oxygen consumption, glucose tolerance,insulin sensitivity, mitochondrial function and
decreased body weight, glucose,insulin, cholesterol, hepatic steatosis, inflammation and oxidative stress
which intern leading to enhanced stress resistance,genome stability,memory and cognitive function, beta
cell function and reduced diet induced obesity, type 2 diabetes, Alzheimer's disease and other
neurological disorder which ultimately leading increased longevity.
By Ayetenew Abita
Submission Date: 04/12/2017