The Mystery of Aging
By Julianne Glaser
No one is spared from the inevitable effects physical aging — aching joints, muscle loss, declining vision, increased fatigue and a multitude of symptoms associated with "getting old." It's a universal human experience that causes myriad changes to our bodies and biological functions. But what causes these changes? Is our life span predetermined by our genes or do our bodies simply wear out over the years?
Two schools of thought theorize what determines how we age and how long we live. One theory is that our bodies are designed to live for a certain number of years based on our genetics. The second theory holds that damage that occurs to our DNA over time accumulates until it's too much to for our bodies to withstand.
Which theory is correct is the subject of debate. If our genes hold the key to our lifespan, then we must be able to modify our genetic "programming" in order to affect the aging process. If aging is the result of accumulated damage to DNA, then the secret to a longer life lies in preventing accumulated damage. In reality, aging is likely the result of both genetics and years of damage to DNA.
Several ongoing studies are exploring ways to slow the aging process and unlock the secrets to longer life with potential keys at the genomic and cellular level.
Controlling Genomic Damage
New research indicates that on the genomic level, aging results in impaired DNA maintenance. DNA accumulates damage and cells enter a senescent, or nonreplicating, state. These senescent cells actually speed the aging process by secreting inflammatory cytokines believed to contribute to tissue atrophy, atherosclerosis and other aging-related diseases.
Impaired DNA maintenance may also result in premature aging diseases, such as progeria and cancer. According to Jan Vijg, a geneticist at Albert Einstein College of Medicine in New York City, “There is this exponential increase in cancer risk during aging, so it’s not at all unlikely . . . that accumulation of damage to the genome is really a major factor...”
Influence of Epigenetics
Epigentics studies the mechanisms that cause cells with identical DNA to develop, appear and function very differently. In a fetus, epigenomes direct development of undifferentiated stem cells at the right time and sequence.
One of the most studied epigenetic mechanisms is DNA methylation where methyl groups attach directly to DNA strands. An equilibrium between methylation and de-methylation directs healthy cell growth and differentiation. An imbalance in DNA methylation has been found in diseases including cancer and autoimmune diseases such as lupus and multiple sclerosis.
Studies are exploring whether external factors such as diet, stress or pollutants could influence epigenomes and speed or slow aging, even when the exposure occurred generations earlier.
Proper Protein Function
Proteins are essential for life but they must be correctly "folded" for proper gene expression, enzyme function, and other essential physiological functions. Research has revealed that protein misfolding accompanies aging, causing misshapen proteins to clump together and inhibit cell function.
“The big open question is whether the accumulation of misfolded protein aggregates is the cause or consequence of the aging process,” says Claudio Soto, a neuroscientist at the University of Texas Health Science Center at Houston . “The hypothesis is that maybe there is a widespread accumulation of misfolded protein aggregates affecting all cells in the body, and that produces progressive dysfunction of cells in the body that leads to aging.”
According to Soto, “Correcting protein misfolding may be a way of staving off a host of age-related maladies or even aging itself; you could envision really intervening and delaying the aging process.”
Mitochondria are the powerhouses that convert nutrients to energy in cells. In contrast to earlier studies, recent evidence indicate that moderate amounts of stress to mitochondria may actually benefit the cell and organism as a whole. “If damage is not too severe, there’s some sort of protective response,” says Toren Finkel, an aging researcher at the National Heart, Lung, and Blood Institute; It appears that “what won’t kill you makes you stronger.”
Though resilient, damage to mitochondria from oxidation can eventually impact cellular function. Mitochondrial damage likely plays a key role in aging given its involvement in metabolism, inflammation and epigenetic regulation of DNA.
Dwindling Stem Cells
In healthy adults, hematopoietic stem cells (HSCs) produce about 200 billion new red blood cells daily, replacing an equal number removed from circulation. For unexplained reasons, the rate of blood-cell production decreases with age.
Harvard's Derrick Rossi and colleagues discovered that even when dormant for extended periods, HCSs are still vulnerable to DNA damage. This results in reduced capacity for DNA repair and eventually a decreased capacity for red blood cell production.
How and why stem cells slow down with age is unknown. According to geneticist Norman Sharpless from the University of North Carolina at Chapel Hill School of Medicine, “Everybody’s got a favorite theory, but it’s sort of an open question.”