What Is the Genetic Theory of Aging?

How Genes Affect Aging and How You May “Alter” Your Genes

Your DNA may predict more about you than the way you look. According to the genetic theory of aging, your genes (as well as mutations in those genes) are responsible for how long you’ll live. Here’s what you should know about genes and longevity, and where genetics fits in among the various theories of aging.

Genetic Theory of Aging

The genetic theory of aging states that lifespan is largely determined by the genes we inherit. According to the theory, our longevity is primarily determined at the moment of conception and is largely reliant on our parents and their genes.1

The basis behind this theory is that segments of DNA that occur at the end of chromosomes, called telomeres, determine the maximum lifespan of a cell. Telomeres are pieces of “junk” DNA at the end of chromosomes which become shorter every time a cell divides. These telomeres become shorter and shorter and eventually, the cells cannot divide without losing important pieces of DNA.2

Before delving into the tenets of how genetics affects aging, and the arguments for and against this theory, it’s helpful to briefly discuss the primary categories of aging theories and some of the specific theories in these categories. At the current time, there is not one theory or even one category of theories that can explain everything we observe in the aging process.

Theories of Aging

There are two primary categories of aging theories which differ fundamentally in what can be referred to as the “purpose” of aging. In the first category, aging is essentially an accident; an accumulation of damage and wear and tear to the body which eventually leads to death. In contrast, programmed aging theories view aging as an intentional process, controlled in a way that can be likened to other phases of life such as puberty.

Error theories include several separate theories including:

• Wear and tear theory of aging
• Rate of living theory of aging
• Protein cross-linking theory of aging
• Free radical theory of aging
• Somatic mutation theory of aging ^{5Oota S. Somatic mutations – Evolution within the individual. Methods. 2019;S1046-2023(18)30382-7. doi:10.1016/j.ymeth.2019.11.002}

Programmed theories of aging are also broken down into different categories based on the method by which our bodies are programmed to age and die.

• Programmed longevity – Programmed longevity claims that life is determined by a sequential turning on and off of genes.
• Endocrine theory of aging
• Immunological theory of aging

There is significant overlap between these theories and even categories of aging theories.

Genes and Bodily Functions

Before discussing the key concepts related to aging and genetics, let’s review what our DNA is and some of the basic ways in which genes affect our lifespan.

Our genes are contained in our DNA which is present in the nucleus (inner area) of each cell in our bodies. (There is also mitochondrial DNA present in the organelles called mitochondria which are present in the cytoplasm of the cell.) We each have 46 chromosomes making up our DNA, 23 of which come from our mothers and 23 which come from our fathers. Of these, 44 are autosomes, and two are the sex chromosomes, which determine if we are to be male or female. (Mitochondrial DNA, in contrast, carries much less genetic information and is received from only our mothers.)

Within these chromosomes lie our genes, our genetic blueprint responsible for carrying the information for every process which will take place in our cells. Our genes can be envisioned as a series of letters that make up words and sentences of instructions. These words and sentences code for the manufacturing of proteins that control every cellular process.

If any of these genes are damaged, for example, by a mutation that alters the series of “letters and words” in the instructions, an abnormal protein may be manufactured, which in turn, performs a defective function. If a mutation occurs in proteins that regulate the growth of a cell, cancer may result. If these genes are mutated from birth, various hereditary syndromes may occur.⁸ For example, cystic fibrosis is a condition in which a child inherits two mutated genes controlling a protein that regulates channels responsible for the movement of chloride across cells in the sweat glands, digestive glands, and more. The result of this single mutation results in a thickening of mucus produced by these glands, and the resultant problems which are associated with this condition.

How Genes Impact Lifespan

It doesn’t take an elaborate study to determine that our genes play at least some role in longevity. People whose parents and ancestors have lived longer, tend to live longer and vice versa. At the same time, we know that genetics alone are not the sole cause of aging. Studies looking at identical twins reveal that there is clearly something else going on; identical twins who have identical genes do not always live an identical number of years.¹⁰

Some genes are beneficial and enhance longevity. For example, the gene that helps a person metabolize cholesterol would reduce a person’s risk of heart disease.

Some gene mutations are inherited and may shorten lifespan. However, mutations also can happen after birth, since exposure to toxins, free radicals and radiation can cause gene changes.¹¹ (Gene mutations acquired after birth are referred to as acquired or somatic gene mutations.) Most mutations are not bad for you, and some can even be beneficial. That’s because genetic mutations create genetic diversity, which keeps populations healthy. Other mutations, called silent mutations, have no effect on the body at all.

Some genes, when mutated are harmful, like those that increase the risk of cancer. Many people are familiar with the BRCA1 and BRCA2 mutations which predispose to breast cancer. These genes are referred to as tumor suppressor genes which code for proteins that control the repair of damaged DNA (or the elimination of the cell with damaged DNA if repair is not possible.)¹²

Various diseases and conditions related to heritable gene mutations can directly impact lifespan. These include cystic fibrosis, sickle cell anemia, Tay-Sachs disease, and Huntington’s disease, to name a few.¹³

Key Concepts in the Genetic Theory of Aging

The key concepts in genetics and aging include several important concepts and ideas ranging from telomere shortening to theories about the role of stem cells in aging.

Telomeres

At the end of each of our chromosomes lies a piece of “junk” DNA called telomeres. Telomeres do not code for any proteins but appear to have a protective function, keeping the ends of DNA from attaching to other pieces of DNA or forming a circle. Each time a cell divides a little more of a telomere is snipped off. Eventually. there is none of this junk DNA left, and further snipping can damage the chromosomes and genes so that the cell dies.

In general, the average cell is able to divide 50 times before the telomere is used up (the Hayflick limit).¹⁴ Cancer cells have figured out a way to not remove, and sometimes even add to, a section of the telomere. In addition, some cells such as white blood cells do not undergo this process of telomere shortening. It appears that while genes in all of our cells have the code word for the enzyme telomerase which inhibits telomere shortening and possibly even results in lengthening, the gene is only “turned on” or “expressed” as geneticists say, in cells such as white blood cells and cancer cells.¹⁵ Scientists have theorized that if this telomerase could somehow be turned on in other cells (but not so much that their growth would go haywire as in cancer cells) our age limit could be expanded.

Studies have found that some chronic conditions such as high blood pressure are associated with less telomerase activity whereas a healthy diet and exercise are linked with longer telomeres.¹⁶ Being overweight is also associated with shorter telomeres.

Longevity Genes

Longevity genes are specific genes that are associated with living longer. Two genes that are directly associated with longevity are SIRT1 (sirtuin 1) and SIRT2.¹⁷ Scientists looking at a group of over 800 people age 100 or older, found three significant differences in genes associated with aging.

Cell Senescence

Cell senescence refers to the process by which cells decay over time. This can be related to the shortening of the telomeres or the process of apoptosis (or cell suicide) in which old or damaged cells are removed.¹⁸

Stem cells

Pluripotent stem cells are immature cells that have the potential to become any type of cell in the body. It is theorized that aging may be related to either the depletion of stem cells or the loss of the ability of stem cells to differentiate or mature into different kinds of cells.¹⁹ It’s important to note that this theory refers to adult stem cells, not embryonic stem cells. Unlike embryonic stem cells, adult stem cells cannot mature into any type of cell but rather only a certain number of cell types. Most cells in our bodies are differentiated, or fully mature, and stem cells are only a small number of the cells present in the body.

An example of a tissue type in which regeneration is possible by this method is the liver. This is in contrast to brain tissue which usually lacks this regenerative potential.²⁰ There is now evidence that stem cells themselves may be affected in the aging process, but these theories are similar to the chicken-and-the-egg issue. It’s not certain of aging occurs due to changes in stem cells, or if instead, changes in stem cells are due to the process of aging.

Epigenetics

Epigenetics refers to the expression of genes. In other words, a gene may be present but can either be turned on or turned off. We know that there are some genes in the body that are turned on for only a certain period of time. The field of epigenetics is also helping scientists understand how environmental factors may work within the constraints of genetics to either protect or predispose to disease.²¹

Three Primary Genetic Theories of Aging

As noted above, there is a significant amount of evidence that looks at the importance of genes in expected survival. When looking at genetic theories, these are broken down into three primary schools of thought.

• The first theory claims that aging is related to mutations that are related to long-term survival and that aging is related to the accumulation of genetic mutations that are not repaired.
• Another theory is that aging is related to the late effects of certain genes, and is referred to as pleiotropic antagonism.
• Yet another theory, suggested based on survival in opossums, is that an environment that poses few hazards to interfere with life expectancy would result in an increase in members who have mutations that slow down the aging process.

Evidence Behind the Theory

There are several avenues of evidence that support a genetic theory of aging, at least in part.

Perhaps the strongest evidence in support of the genetic theory is the considerable species-specific differences in maximal survival, with some species (such as butterflies) having very short lifespans, and others, such as elephants and whales, being similar to ours.²² Within a single species, survival is similar, but survival can be very different between two species that are otherwise similar in size.

Twins studies also support a genetic component, as identical twins (monozygotic twins) are much more similar in terms of life expectancy than are non-identical or dizygotic twins.²³ Evaluating identical twins who have been raised together and contrasting this with identical twins who are raised apart can help to separate out behavior factors such as diet and other lifestyle habits as a cause of family trends in longevity.

Further evidence on a broad scale has been found by looking at the effect of genetic mutations in other animals.²⁴ In some worms as well as some mice, a single gene mutation may lengthen survival by over 50 percent.

In addition, we are finding evidence for some of the specific mechanisms involved in the genetic theory. Direct measurements of telomere length have shown that telomeres are vulnerable to genetic factors that can speed up the rate of aging.

Evidence Against Genetic Theories of Aging

One of the stronger arguments against a genetic theory of aging or a “programmed lifespan” comes from an evolutionary perspective. Why would there be a specified lifespan beyond reproduction? In other words, what “purpose” is there for life after a person has reproduced and been alive long enough to raise their progeny to adulthood?

It’s also clear from what we know about lifestyle and disease that there are many other factors in aging. Identical twins may have very different lifespans depending on their exposures, their lifestyle factors (such as smoking) and physical activity patterns.

The Bottom Line

It’s been estimated that genes can explain a maximum of 35 percent of lifespan, but there is still more we do not understand about aging than which we do understand.²⁵ Overall, it’s likely that aging is a multifactorial process, meaning that it is probably a combination of several of the theories. It’s also important to note that the theories discussed here are not mutually exclusive. The concept of epigenetics, or whether or not a gene that is present is “expressed” can further muddy our understanding.

In addition to genetics, there are other determinants of aging such as our behaviors, exposures, and just plain luck. You are not doomed if your family members tend to die young, and you can’t ignore your health even if your family members tend to live long.

What Can You Do to Reduce the “Genetic” Aging of Your Cells?

We are taught to eat a healthy diet and be active and these lifestyle factors are likely just as important no matter how much our genetics are involved in aging. The same practices which seem to keep the organs and tissues of our bodies healthy may also keep our genes and chromosomes healthy.

Regardless of the particular causes of aging, it can make a difference to:

• Exercise – Studies have found that physical activity not only helps your heart and lung function well, but exercise lengthens telomeres.¹⁶
• Eat a healthy diet – A diet high in fruits and vegetables is associated with greater telomerase activity (in effect, less shortening of the telomeres in your cells). A diet high in omega-3-fatty acids is associated with longer telomeres but a diet high in omega-6-fatty acids is the opposite and associated with shorter telomeres. In addition, soda pop intake is linked with shorter telomeres. Reservatrol, the ingredient responsible for the excitement over drinking red wine (but also found in non-alcoholic red grape juice) appears to activate the longevity protein SIRT
• Reduce stress²⁶
• Avoid carcinogens
• Maintain a healthy weight – Not only is obesity linked with some of the genetic mechanisms associated with aging noted above (such as increased shortening of telomeres), but repeated studies have found longevity benefits associated with caloric restriction.²⁷ The first principle in the cancer prevention lifestyle put forth by the American Institute for Research on Cancer—be as lean as possible without being underweight—might play a role in longevity as well as cancer prevention and the prevention of cancer recurrence.