Aging: Molecular insight

When Adwaita died, he was 250 years old; remarkable isn’t it? He was a tortoise. The freshwater pearl mussel may live for 200 years. Various trees, such as the bristlecone pine, the giant sequoia, live for 1000 of years. Yet humans, who are generally considered to be at the apex of terrestrial life, do well to live for 80 or 90 years despite our sometimes extraordinary efforts to extend the life! Mammalian gerontologists usually define aging in terms of the gradual, insidious, and progressive declines in structure and function that begin to unfold after the achievement of sexual maturity. The decline at cellular level affects the germ line as well as the soma. Ageing is among the largest known risk factors for most human diseases.[1]

The biogerontologistsfirst came out with the Evolutionary theory of aging hypothesis based on the fact that aging evolved due to the species selective advantage. Overtime, however, theories have undergone dichotomy of sorts, and divided into damage based in which aging occurs as part of the accumulative effect of cell by products or inefficient repair/defensive systems. Whereas Programmed based theories focus on a stochastic process or random series of timed process causing genetically triggered cellular senescence and eventually organism death.

The mechanisms of aging are basically divided into three sets. Initiator trigger mechanisms include some of the most significant breakthrough in the systematic analysis of aging process. Genome flux is all about gate keeper genes and care taker genes, inclusive of the putative DNA repair genes and the mismatch, nucleotide excision and repair genes. Telomere wear and tear involves the telomerase enzyme gradually loosening its effect on cells. The initiator trigger mechanism malfunctions lead to numerous progroid syndromes such as Xeroderma pigmentosa, Cockayne syndrome, Blooms syndrome, Hutchinson Gilford Progeria, Werner syndrome, etc.[2]

The secondary subsets are known as the reactionary shield mechanisms, which cause response to the damages, which include Malfunctioning nutrient - cell signals, Mitochondrial break down, and cellular senescence. Malfunctioning nutrient - cell signals is all about caloric restriction which in turn means regulation of DAF 16 by insulin/insulin growth factor 1 (IIS pathway), IIS stimulation tends to promote aging by inhibiting DAF16 pathway, which helps build antioxidants, heat shock proteins. Caloric restriction also promotes build-up of sirtuins and FOXO and inhibition of TOR, ultimately improving mitochondrial function and promoting longevity.[3]

The third subset can be best termed as the culprits of the phenotype changes, and include the stem cell fatigue and flawed intercellular communications. The compelling evidence found in Drosophila intestinal stem cells suggests that the stem cells quiescence for prolonged intervals holds the key to long-term functionality of stem cells.[4]

Identifying and defining the hallmark regulators of aging will help build a road map for the potential research emanating on the molecular concepts of aging and will ultimately procreate a major impact on human health and longevity. On a lighter note, scientists claim that good indicators of longevity are conscientiousness and having a large number of social ties. “Conscientious people do more things to protect their health and engage in fewer activities that are risky”. The adage “the good die early and the bad die late,” crumbles under scientific scrutiny, say the authors. “Generally speaking, the bad die early, and the good do great.” [5]