A Study of the Aging ProcessJorge Roman, Department of Biological Sciences, College of Arts and Science & Honors College

Faculty Mentor: Edward Dzialowski, Department of Biological Sciences, College of Arts and Sciences

There are many theories as to why the biological process of aging takes place. The free radical theory postulates that organisms age due to the buildup of free radical damage over time. Free radicals are any number of atoms or molecules that have an unpaired electron in their outer shell. For biological organisms, free radical damage is associated with oxidative damage. Antioxidants act as reducing agents that limit oxidative damage. In theory, reducing oxidative damage should increase the lifespan of an organism. Free radicals are only one factor in the aging process. Another key contributor to aging lies within genes. Organisms are preprogrammed to age and eventually die to ensure that evolution can occur. Humans age progressively over time due to the presence of protein ∆50 lamin A, which sensitizes the structure of a cell. Over time cells become more prone to oxidative damage from free radicals and this results in aging. Although there are factors that contribute to damage.

• A study concerning antioxidants and their effects on aging found that the antioxidants had remarkable effects on aging as well as age-related disorders.

• The antioxidants were tested on mice, drosophila, and daphnia. In all the tests the antioxidants inhibited several age related disorders. The cells treated with antioxidants showed increase resistance to induced apoptosis via hydrogen peroxide. (Skulachev, 2007)

• Research concerning protein lamin A involved observing subjects with an accelerated aging disorder known as progeria. The subjects with progeria exhibited overproduction of protein lamin A.

• By studying subjects with progeria the researchers were able to deduce the role of protein lamin A within the cell. The over-production of lamin A caused malformations in cell structure. (Taimena, 2009)

• A study was performed in order to assess lamin A and its connection with aging. The study found a relationship between levels of a type of lamin A, ∆50 lamin A, and rates of aging.

• In subjects with progeria, the accelerated aging disorder there are high levels of ∆50 lamin A present. ∆50 lamin A is present in low levels in normal cells. The researchers formulated a theory that ∆50 lamin A could possibly make a cell more prone to aging by sensitizing its overall structure. (Kudlow & Kennedy, 2006)

Kudlow, B., & Kennedy, B. (2006). Aging: progeria and the lamin connection. Current Biology, 16(16), Retrieved from http://www.sciencedirect.com/science?_ob=MImg&_imagekey= B6VRT-

4KPFVNM-P-1&_cdi=6243&_user=10&_pii=S0960982206018963&_ coverDate=08%2F22%2F2006&_sk=%23TOC%236243%232006%23999839983%23630451%23FLA%23display%23Volume_16,_Issue_16,_Pages_1581-1684_22_August_2006)%23tagged%23Volume%23first%3D16%23Issue%23first%3D16%23 date%23(22_August_2006)%23&view=c&gw=y&wchp=dGLzVtb- zSkWz&md5=d3dbedb49afb777f55ca02a9c3cef3b0&ie=/sdarticle.pdf Skulachev, V. (2007). A Biochemical approach to the problem of aging: "megaproject" on membrane

penetrating ions. The first results and prospects. Biochemistry, 72(12), Retrieved from http://dq4wu5nl3d.search.serialssolutions.com/?genre=article&isbn=&issn=00062979&title=Biochemistry+(00062979)&volume=72&issue=12&date=20071201&atitle=A+biochemical+approach+to+the+problem+of+aging%3a+%e2%80%9cMegaproject%e2%80%9d+on+ membrane

penetrating+ions.+The+first+results+and+prospects.&aulast=Skulachev%2c+V.&spage=1385&sid=EBSCO:Academic+Search+Complete&pid=

 Taimena, P. (2009). A Progeria mutation reveals functions for lamin a in nuclear assembly, architecture,

and chromosome organization. Proceedings of the National Academy of Sciences of the United States of America, 106(49), Retrieved from

http://www.pnas.org/content/106/49/20788.full.pdf+html

Images:

"Antioxidant effects table." Adapted from “A Biochemical approach to the problem of aging: "megaproject" on membrane penetrating ions. The first results and prospects.” by Skulachev, V., 2007, Biochemistry, 72(12), pg 1394.

"Cell apoptosis charts." Adapted from “A Biochemical approach to the problem of aging: "megaproject" on membrane penetrating ions. The first results and prospects.” by Skulachev, V., 2007,

Biochemistry, 72(12), pg 1393. "Control cells versus mutant cells." Adapted from “A Progeria mutation reveals functions for lamin a in

nuclear assembly, architecture, and chromosome organization.” by Taimena P., 2009, Proceedings of the National Academy of Sciences of the United States of America, 106(49), pgs. 20790-20791. "D50 lamin A aging.." . Adapted from “Aging: progeria and the lamin connection.” By Kudlow B. and

Kennedy B., 2006, Current Biology, 16(16), pg R653.

ABSTRACT

LITERATURE REVIEW

REFERENCES

METHODOLOGY• A relationship can be established between the free radical theory of

aging and protein lamin A, specifically ∆50 lamin A. In the process of normal aging, low levels of ∆50 lamin A over time continuously weakens the structure of the overall cell. • By making the cell weaker free radicals have the opportunity to

induce more damage.• The antioxidant treatment has the potential to act as a treatment for

people with progeria.• Further studies need to be conducted to assess why some people

age better than others. Genetic analysis of these individuals could reveal new information with respect to aging.• I will explore the feasibility of a study examining the effects of lamin

A therapy on aging in mammals.

Cell Apoptosis Charts

Test results for induced cell apoptosis. Cells treated with antioxidants showed increase apoptosis resistance.

Antioxidants Effects Table

Table listing the various antioxidant effects on the animal test subjects.

Control Cells versus Mutant Progeroid Cells

∆50 lamin A and aging

Model showing the relationship between aging and the levels of ∆50 lamin A.

Stained cells show the differences in overall cell structure of normal cells versus those of progerian cells.

ACKNOWLEDGEMENTS Wendy K. Wilkins, Ph.D., Provost and Vice President for Academic Affairs Gloria C. Cox, Ph.D., Dean, Honors College Susan Brown Eve, Ph.D., Associate Dean, Honors College

Edward Dzialowski, Ph.D, Department of Biological Sciences, College of Arts and Sciences

Pamela Padilla, Ph.D., Department of Biological Sciences, College of Arts and Sciences