The Science of Aging Why We Grow Old and Die

Sections The Aging Process: Basics The Cell Cycle and Mutation Stem Cells, Gene Activity and Methylation Sites Telomere Degradation Interaction with Our Environment Aging Anomalies and Extending Human Life

Key Question: When DNA from these individuals are compared side by side, only 1.15 bases out of a thousand are different. Yet given this striking similarity, one human’s life is just beginning, while the others is coming to an end… ….WHY?

Aging Basics The average human is composed of 100 trillion cells. Cellular Senescence or biological aging is the gradual deterioration of lifeforms at the cellular level, that results in mortality. The word "senescence" essentially refers to the phenomenon in which normal diploid cells cease to divide.

Aging Basics (Cont.) fibroblasts (connective tissue cells that generate pliability in the skin) can reach a maximum of 50 cell divisions before becoming senescent. Neurons are innately senescent. While some other cells divide thousands of times. Erythrocytes never divide. An array of senescence exists among the thousands of cell types in the human body, yet they’re governed by a few natural phenomenon…

The cell Cycle and Mutation Cells are governed by the Cell Cycle, which, depending on cell type, will determine if a cell divides or undergoes apoptosis (programmed cell death). Often times this is appropriate, but in damaged cells usually happens prematurely.

The cell Cycle and Mutation Mutations (random errors in DNA replication) build up every day in any organism….the product of the numerous cell divisions that keep us alive. Although the vast majority are harmless, some can disrupt the cell cycle…

The Cell Cycle and Mutation Although governed by 50+ “proofreading” enzymes that continuously patrol our newly formed DNA, “Free radicals” and random errors persist and are preserved in the genome…. Mutations in the genes that code for the proofreading enzymes themselves are particularly deleterious.

The cell Cycle and Mutation: the END Game Apoptosis occurs prematurely or inappropriately in cells with altered genes. Mutations trigger regulatory enzymes which not only inhibit expression, but illicit a cascade of events which will kill the cell and prevent it from replicating. Over time, mutations accumulate in our genome. Apoptosis is more pervasive, cell functionality decreases, and senescence abounds.

Stem Cells Stem cells are essentially generic ‘starter cells. They are “pluripotent” meaning have the potential to develop into different cell types in the body. When division occurs, subsequent cells can remain as stem cells, or under certain conditions become a specific cell type.

Stem Cells Stem cells decrease as we age, although even the all adults retain stem cells in spinal tissue and Hematopoietic tissue within red marrow. Although Embryonic stems cell research is controversial, the potential for their use in tissue regeneration is exceptionally promising.

MHC = Mesenchymal Stem cells

Gene Activity and Methylation sites DNA methylation is a process by which methyl groups are added to DNA on cytosine monomers. Methylation modifies the function of the DNA, typically acting to suppress gene transcription

Gene Activity and Methylation sites Although every person's DNA remains the same throughout their lives, gene expression functions differently as we age. Changes appear in DNA methylation patterns as we grow older, scientists believe these act as a "secondary code" on top of our DNA that lock genes in the “on” or “off” position, governing their expression.

Telomere Degradation Telomeres represent portions of DNA and protein present at the tips chromosomes. Telomeres prevent them chromosomal degradation and end- to-end fusion during cell division. Mammalian DNA consists of the 6 base sequence “TTAGGG” repeated thousands of times.

Telomere Degradation The enzymes associated with DNA replication cannot function at the very tips of chromosomes, therefore, tiny portions of our chromosomes are left every time a cell divides. As a result, these non-coding regions become shorter and shorter as cell divisions increase accumulate over time. Eventually, senescence becomes inevitable.

Interaction with our environment Human behaviors can accelerate the rate of mutation within our genes, subsequently increasing the likelihood of apoptosis and cancer. More generally, “overworking” specific organs in various capacities can result in failure and premature death.

Aging Abnormalities While a number of factors limit the lifespans of different organisms, some have evolved remarkable genetic mechanisms which extend life considerably. In particular scientists have focused on mapping the genomes of Bowhead whales and Galapagos tortoises. These animals can live over 200 years and 170 years respectively. Why?....

Aging abnormalities Although slower metabolic rates within the cells of these organisms slows senescence. Over a dozen unique genes have been discovered within their respective genomes which repair DNA, and regulate the cell cycle much more efficiently (as compared to similar vertebrates), extending life considerably. Link: http://www.slate.com/articles/health_and_science/science/2015/01/longest_living_mammal_on_earth_bowhead_whale_s_genome_gives_clues_about.html

Did you know? A koi fish named Hanako holds the record as the longest lived vertebrate in recorded history. Dying at the age of 226 years. Hanako was born in 1751, and died in 1977.

Extending human life Modern health and hygiene, coupled with significant advances in medicine have extended human life dramatically over the last 200,000 years. Although still the stuff of science fiction, the potential for transgenic advances capable of extending human life are quite real…