The Science of Aging

The Universal Truth

There’s one Truth for all in this life and that is, no one gets out alive! Aging is a natural fact of life and how we do it the big question. Slowing down the rate at which we age and succumb to disease and eventually death is a multi-hundred-billion-dollar business- the “appearance market” alone is estimated to reach $119.6 billion by 2030 (Precedence Research, March 2022).

To embark on this article, I did some reading and asked some questions. After twenty years in the Esthetics business, what I thought I knew about aging I realized was a little… shallow. When I heard the word, I automatically thought about dry skin, wrinkles, hyperpigmentation. Gray hair, weak bones, and muscle atrophy. Poor eyesight, hearing and cognitive decline, inevitable. I really didn’t think about aging at the cellular level. After this exploration, all the above “side effects” of aging make a lot more sense. For the purposes of this writing, I will clarify that “aging” is inclusive of all the body systems, down to the cellular level.

An important topic like this one has multiple theories and a deep well of research studies and papers to explain why we age. According to 13-year-old Rory Carter, “Everyone has an expiration date. When it’s up, we die.”  Pop culture entertainer, Dr. Oz, has an Anti-Aging Plan with product recommendations and dietary inclusions that claim to take seven years off your appearance. Even the “Medical Medium” has a chapter on aging. According to his book, the liver is solely responsible for the aging processes in the body- right down to DNA function (William, 2018). There are many more theories out there about what products we can buy, foods we can eat, diets to crash, procedures to invest in. I found there are a lot of theories on aging that discuss exposure to unstable “free radicals” and aging interventions like “antioxidants”, but before we talk about environment, we must start at the source- and that is in our DNA.

It’s in our nature to age…

The fact is, we were born to die. As our lives and time go on, our bodies more (or less) naturally age. Cell division slows, the body’s rate of repair suffers, and diseases of aging take hold. The Rate of Living Theory, or “Wear and Tear Theory”, suggests that we all have a specific amount of energy that can be used for cell division. When that limit is reached, cell death and system break down is inevitable. In looking at a maladaptation of aging, Progeria, (think Benjamin Button) a gene mutation is responsible for accelerating aging due to an abnormal protein causing cell break-down, so we know not everyone ages according to time on planet earth. Another cellular aging theory was born out of the Hayflick study that revealed that cells may be programmed to die, specifically after 40-60 divisions (Bartlett, 2014).  Some of these dead cells get removed by the lymphatic system while others become “senescent” or deactivated cells.  The Hayflick Limit Theory explains the body’s natural defense against certain diseases of replication like cancer. The other side of cellular senescence is cell inactivity which limits cellular repair mechanisms and opens the body up for a variety of age-related symptoms and diseases (M. Youselfzadeh, et al 2021).  What’s further is these senescent cells give off chemicals like inflammatory cytokines that are thought to cause aging, much like a free radical. Programmed Cell Death theory may very well account for diseases of aging, as when cells “self-destruct” we see conditions such as Alzheimer’s with the physical manifestation of neural death and resulting brain shrinkage.

 But what triggers the process?

What we do know is that mesenchymal stem and stromal cells respond to transcription factors from a gene called GATA6 (Hongli Jiao et al 2020). The GATA6 gene can turn on or off cellular activities of aging. What begins the cellular changes in the DNA that causes the cascade of aging processes may have something to do with some inherited factors from our mother. Passing down codes in the mitochondrial nucleus may have an influence over the energy a cell is able to maintain to divide for a longer period. A study from 2013 found that mitochondrial DNA has a stronger blueprint for aging than nuclear DNA (Ross et al 2013). Mutations here cause an eventual demise of the cell’s energy producing capabilities with ATP. Cellular energy has a direct impact on its ability to divide and therefore repair and regenerate. If it’s triggered early, what we see is considered premature aging, if it’s triggered late, we consider that person to be aging well.

So, why do some people age better than others?

There are two theories in geroscience that covers the many aspects of the biological aging process, inclusive of both natural and environmental factors. Lopez-Otin et al, have identified nine Hallmarks of Aging. The Seven Pillars of Aging theory out of the Franceschi study of 2018, focuses more on “inflammaging” and how that relates to aging processes. Understanding these pillars may lay the path for future interventions that increase the healthy years of our lifespan, also known as “healthspan”. To reiterate, the difference between the Nine Hallmarks and the Seven Pillars comes down to the latter’s focus on inflammation processes.

 We have heard a thousand times; free radicals cause cellular damage that accelerate the aging process. They have been shown to trigger gene mutations that accelerate the aging process. Science has attempted to answer the aging riddle through the study of identical twins to see how much of aging is genetic and how much is environment. The identical twin studies have shown that even with identical DNA, individuals age differently. Also shown are promising insights such as age-related traits and age-related diseases are more heritable than non-age-related diseases, such as breast cancer. Interesting to note the high heritability of Alzheimer’s dementia at 79% and hip fracture <69 years old at 68% (Steves et al 2012). Ultimately, how our bodies react to insults from our surroundings and respond can be seen at the cellular level right down to the DNA. Here is where we see this intersect between biology and environment.

It is also undeniably environmental

Nurture comes down to environment and to me, that is heavily influenced by social factors.  I’m not referring to Muffie on her yacht in the South of France- martini in one hand and hauling on her Barclay 100s from the other. In the last few years an emerging area of focus in social determinants of health (SDOH) have been acknowledged and woven into educational programs for caregivers to address the issue. Health.gov has identified SDOHs as Economic Stability, Education Access & Quality, Health Care Access & Quality, Neighborhood & Built Environment and Social & Community Context. All of these are not only highly interrelated but create a compromised health picture from early in life that is associated with not only aging, but all health outcomes. Crimmins calls this complex reality “Downstream Biology”. (Crimmins, 2020). To summarize the concept, if you are of a lower socio-economic status, you are sadly more at risk of exposures from “upstream” that are associated with triggering the aging process in the cell’s DNA. To follow suit, you are also less likely to afford or seek the needed or desired health care and/ or interventions to interrupt the process.

It’s all interrelated

Genetics, social factors, biological cell behavior, environmental exposures- all play a role in either triggering the aging process or slowing it down. It’s therefore difficult to separate which aspect of cell deterioration contributes most to aging. According to the Kennedy study, the main driver of aging, which is the cellular response to DNA damage, is genetically determined (Kennedy, 2014). According to Honors Biology Educator Karalynn Gauvin, environmental factors damage our DNA, and that damaged DNA is passed on to subsequent generations of cells. Damaged cells then struggle with protein synthesis and tissue repair- a distilled snapshot of the aging process.

One of the areas of research that could prove beneficial in the anti-aging movement is how we can use nurturing lifestyle and product interventions to limit mitochondrial mutations that are in our nature. It is important to note the challenge of conducting longitudinal studies on how humans age due to our long lifespan. The Jiao et al study from 2020 has brought forward new insight on how reprogramming stem cells were able to hold off, and even repress, age-related cellular activities greater than the original stem cells. The difficult task remains making health care and anti-aging interventions available to all equally.

References

Precedence Research Anti-aging Market Size to Worth Around US $119.6 By 2030, March 29, 2022

Anthony William Liver Rescue October 2018, Hay House

Bartlett, Zane, "The Hayflick Limit". Embryo Project Encyclopedia (2014-11-14). ISSN: 1940-5030 http://embryo.asu.edu/handle/10776/8237.

M. Youselfzadeh, C. Henpita, R. Vyas, C. Soto-Palma, P. Robbins, L. Niedernhofer, (2021) DNA damage-how and why we age?  eLife 10:e62852 https://doi.org/10.7554/eLife.62852

Hongli Jiao et al. GATA6 regulates aging of human mesenchymal stem/stromal cells. Stem Cells, published online November 30, 2020; doi: 10.1002/stem.3297

C. López-Otín, M.A. Blasco, L.Partridge, M. Serrano, G. Kroemer, The hallmarks of aging

Cell, 153 (2013), pp. 1194-1217, 10.1016/j.cell.2013.05.039

C. Franceschi, P. Garagnani, P. Parini, C. Giuliani, A. Santoro Inflammaging: a new immune-metabolic viewpoint for age-related diseases

Nat. Rev. Endocrinol., 14 (2018), pp. 576-590, 10.1038/s41574-018-0059-4

Jaime M. Ross, James B. Stewart, Erik Hagström, Stefan Brené, Arnaud Mourier, Giuseppe Coppotelli, Christoph Freyer, Marie Lagouge, Barry J. Hoffer, Lars Olson, Nils-Göran Larsson. Germline mitochondrial DNA mutations aggravate ageing and can impair brain development. Nature, 2013; DOI: 10.1038/nature12474

Claire Joanne Steves, Timothy D. Spector, Stephen H. D. Jackson, Ageing, genes, environment and epigenetics: what twin studies tell us now, and in the future, Age and Ageing, Volume 41, Issue 5, September 2012, Pages 581–586, https://doi.org/10.1093/ageing/afs097

University Hospitals Case Medical Center. (2013, August 21). Mother's genes can impact aging process. ScienceDaily. Retrieved June 1, 2022 from www.sciencedaily.com/releases/2013/08/130821132710.htm

E. Crimmins Social hallmarks of aging: Suggestions for geroscience research, Ageing Research Reviews, Volume 63, November 2020

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