4.3.2.

5 Size Does Matter

Topic Summary of Research Article and Publication Data (APA format)
Aging Aging is a gradual process that results in dysfunction and reduced reserve capacity of all body organs.
It occurs at the cellular level and reflects both a genetic program and cumulative environmentally
imposed damage. Mammalian cells can undergo only a limited number of cell divisions and then arrest
irreversibly (Hayfick and Moorehead, 1961, Hayflick, 1965, Hayflick, 1977) in a state known as
replicative senescence, after which they are refractory to mitogenic stimuli. Age-associated changes in
pattern of gene expression and cellular proliferative capacity appear largely under the control of the
telomeres. Telomeres are the ends of linear chromosomes, several thousand bases in length that
consist of tandem repetitive DNA sequences. The 3′ strand has in mammals the sequence (TTAGGG)n
and extends 75–300 bases beyond the complementary 5′ strand, leaving a single-stranded G- rich
overhang at the very end. It is clear that telomere-based signaling plays a crucial component in this.
Progressive telomere shortening, which is exacerbated by low grade oxidative damage to telomeres
and other cellular components as a result of aerobic cellular metabolism, essentially regulates intrinsic
aging. UV radiation also damages DNA and speeds up telomere shortening in skin that has been
exposed to the sun. The last step of aging and photodamage appears to include signaling through p53
after telomere breakage. These and other insights into the molecular foundation for skin
aging/photoaging may lead to improved management choices. These telomere-initiated reactions, in
combination with UV-induced damage to crucial regulatory genes, lead to the recognized appearance
of "photoaging."

Disease The World Health Organization (WHO) estimates that the incidence of infants born low birth weight
(LBW) in North America is approximately 7% and is commonly characterized as a birth weight under
2500 g. A further sub classification within the LBW classification is that of intrauterine growth
restriction (IUGR) where a fetus fails to reach its genetic growth potential, as a result of a
compromised intrauterine environment and is generally defined as being less than the 3rd percentile
of normal birth weight. IUGR can be caused by a heterogeneous mix of fetal, placental and maternal
factors. Fetal factors include genetic abnormalities, multiple gestation, and infections, while maternal
contributing factors for IUGR include malnutrition, drug intake, hypertension, Type I or gestational
diabetes, and persistent hypoxia due to cardiovascular disease or high altitude.