Mystery of Life

Mystery of Life

Human Genetics

Aging begins at conception.

Age 30 seems to be the turning point of decline.

Individuals are functionally less efficient 0.8% each year

Death rate rapidly begin to increase after puberty

Log scale Gompertz plotting

Strait line from 15 to 90 years

Death rate doubles every 8 years

Fibroblast Aging

Telomere depletion hypothesis

Iso base pair position of the telemere cap is lost in each subsequent division

Cancer cells appear to avoid telemere shortening

Capping done by the enzyme telemerase

Telemerese is arrested but the results unequivocal

Only 20 cell generations were added.

It is strange all cells of living beings last only 50 cell cycles.

In human 42 to 45 are finished by puberty and we have 5 cell cycles to live after puberty.

This is universal in all larges animals but the inter-phase between cell cycles determine the life span of any individual.

Why this is finite is unknown.

Wear and Tear Hypothesis

Collagen and elastic fibers

Aging cells accumulate damage (DNA repair is defective)

Free radical damage

Non enzymatic process called glycation

Gene Clock Hypothesis

Centerarie

Werner Syndrome

Premature aging plus cancer

Defect in helicase enzyme involved in DNA repair.

Helicase enzyme is necessary to unwind the DNA double helix whenever DNA has to be replicated, repair or translocated.

Indy-I am not dead yest

37 days to 70 years.

Centenarians

Single gene implicated

Affects

1. Insulin secretion and glucose metabolism

2. Immune System

3. Cell Cycle

4. Lipid Metabolism HDL

5. Response to stress

6. Production of anticoagulant enzymes

In other words, the older one gets, the healthier one becomes.

This why I say, if one could pass 65 years without disease or drugs, it is hard to kill one (only by medical misadventure).

Mitochondrial Genetics

non Mendelian genetics, the law of absence of segregation

Mitochondria contain 37 genes

Copies as mini chromosomes.

Several copies of mini chromosomes.

Maternally inherited

Paternal mitochondria selectively destroyed in early development.

Mitochondrial DNA does not cross over.

Mitochondrial DNA does not have repair enzymes.

Mitochondrial DNA does not mutate faster

Free radicals in mitochondria damages DNA.

No histone proteins.

No introns.

Many mitochondria

37 genes.

22 transfer RNAs

13 genes that encodes for proteins that functions in cellular respiration.

Diseases first recognized in 1962.

Mitochondrial myopathies.

Weakness fatigue, flaccidity

Lhon Leber’s hereditary optic neuropathy.

MELAS

Mitochondrial Myopathic encephalopathy

Lactic Acidosis syndrome.

Ooplasmic transfer.

Heteroplasmy.

Mitochondrial replication occurs with the participation of the nuclear genes

Mitochondria cannot be grown without cell infrastructure (Symbiotic becoming completely parasitic)

Some of the mitochondrial DNA has become translocated into the chromosomal DNA in evolution.

Oxidative phosphorylation requires at least 69 polypeptides

13 = 1 cytochrome b

2 ATPases subunits

3 cytochrome c oxidases

7 subunits of NADH dehydrogenases

Mitochondrial ribosomal RNA is more similar to prokatotic ribosomal RNA

Sensitive to streptomycin/chromphenicol antibiotics

Inhibit their functions

Strong support for symbiotic origin of mitochondria

Lynn Marguiles (who committed suicide, my memory needs confirmation)

Exception is yeast

Yeast mitochondria are 5 times larger and have introns

These genes probably arise from nude DNA and later captured by mitochondria

The ten mysteries that I have not yet worked out.

The greatest mystery is the origin of the first successful cell with the union of prokaryotic bacteria (mitochndria within a cell without a cell wall) and cellular DNA to form an Eukaryotic cell.

1. Origin of Zero

2. Origin of Dogs from the Wild

3. Sex differentiation in cells

4. Matter and antimatter

5. Levo-rotation of molecules

6. Superconductivity at absolute zero temperature

7. Left and right orientation of brain

8. Origin of language

9. Proton spin

10 Viral flu