The researchers of a new publication take a look at the effects of obesity on aging and consider its impact in the context of the Hallmarks of Aging, a popular theory that breaks down aging into nine distinct processes.
The case for obesity accelerating aging
Being overweight and carrying excessive amounts of visceral fat, a type of body fat that is stored in the abdominal cavity and surrounds a number of important internal organs, such as the liver, pancreas, and intestines, is known to increase the risk of age-related diseases.
The more overweight a person is, and thus the more visceral fat that person has, the worse the impact on health tends to be. That said, even being moderately overweight is still harmful to health, and there is a myriad of epidemiological studies supporting this.
So does this mean that obesity speeds up the rate at which we age? This is exactly what these researchers set out to answer, and, surprisingly, it is not entirely black and white. Biology, particularly the biology of aging, has a lot of nuances and confounding factors, so trying to answer this question is difficult.
The Hallmarks of Aging describes telomere attrition as the gradual loss of the protective caps of our chromosomes . Telomere attrition limits the number of times our cells can divide, slowly leading to dwindling populations of cells in vital organs.
Telomeres are the caps at the end of each strand of DNA, like the aglets at the ends of shoelaces, that protect our chromosomes from deterioration or from fusion with neighboring chromosomes. Telomeres are comprised of a specific DNA sequence that is repeated thousands of times.
This sequence serves two purposes: it protects the coding regions of the chromosomes and prevents them from being damaged, and it acts as a clock that controls the number of replications that a cell can make and influences the epigenetic state of the cell.
In most cells, replication causes telomeres to shorten with each division. As we age and our cells divide, the telomeres in these cells eventually become critically shortened, which triggers them to enter senescence; under normal circumstances, such cells destroy themselves via a process known as apoptosis. Obesity is known to promote inflammation and oxidative stress, which is likely to accelerate the rate at which telomeres shorten. There is an association between obesity and telomere length, albeit only a moderate one.
A dedicated review of the possible links between obesity, telomeres, and aging concludes: “obesity may affect telomere dynamics and accelerate the aging process”. We feel that although the results cumulatively show a tendency toward an inverse correlation between obesity and telomere length; it is more prudent to conclude that the available studies are heterogeneous and show a weak statistical significance.
Epigenetic alterations, as described in the Hallmarks of Aging, are age-related changes in gene expression that harm the fundamental functions of cells and increase the risk of cancer.
The DNA in every one of our cells is identical, with only small variations, so why do our various organs and tissues look so different, and how do cells know what to become?
This is how a cell in the liver knows that it needs to develop into a liver cell: the epigenetic instructions make sure that it is given the right orders to become the correct cell type.
At a basic level, these epigenetic instructions make sure that the genes needed to develop into a liver cell are turned on, while the instructions specific to other types of cells are turned off. Imagine if a heart cell were given the wrong instructions and became a bone cell!
The aging can cause changes to our epigenome, which then lead to alterations in gene expression that can potentially change and ultimately compromise cell function. Diet, lifestyle, environment, and various factors contribute to changes to the epigenetic state of cells and obesity likely has an impact on how fast these changes occur.
Several reports demonstrate that nutrition and obesity are able to modulate the epigenetic signature of an individual, even during prenatal development. The observed alterations do not always overlap those seen in aging, however, some studies show a close correlation between epigenetic alteration induced by obesity and acceleration of tissue aging. This suggests that obesity could accelerate age-related dysfunction by inducing epigenetic alterations that are not necessarily the same as those observed during aging in non-obese individuals.
Mitochondrial dysfunction is one of the root causes of aging as described in the Hallmarks of Aging. As they age, mitochondria lose their ability to provide cellular energy and release reactive oxygen species that harm cells.
Mitochondria, which are often called the powerhouses of cells, act like miniature factories, converting the food we eat into usable energy in the form of a chemical called adenosine triphosphate (ATP). ATP provides energy to fuel myriad cellular processes, such as muscle contraction, nerve impulse propagation, and protein synthesis. ATP is common to all forms of life and is often referred to as the “molecular unit of currency” of intracellular energy transfer.
Aging causes changes to our mitochondria that impair their ability to produce ATP efficiently while increasing the release of reactive oxygen species, a byproduct of energy production that becomes excessive in aged mitochondria. The reactive oxygen species then bounce around the inside of the cell and can strike the vulnerable mitochondrial DNA (mtDNA), which is outside the cell nucleus and not protected. The result of a strike can damage the mitochondrial DNA, leading to mutations and making the mitochondria dysfunctional and less able to produce energy.
While most of these issues are detected by quality control mechanisms in the cell, where damaged mitochondria are destroyed through a process called mitophagy, these systems become less and less effective with age, eventually allowing errors to slip through and mutant mitochondria to remain at large.
Normally, this isn’t a huge problem; each cell contains a vast number of mitochondria, so even a few hundred being mutated isn’t an issue. However, sometimes, these mutations can make these mitochondria survive longer than regular mitochondria. In this way, some types of dysfunctional mitochondria build up and eventually become more common than healthy ones.
Mitochondrial dysfunction occurs in aged tissues, in response to excessive nutrient intake, and in obesity, contributing to inflammation and insulin resistance. Aging and obesity appear superimposable in their impact on mitochondria and it is reasonable to hypothesize that they could exert additive effects.
The Hallmarks of Aging describes dysfunctional senescent cells, which promote other hallmarks and encourage other cells to become senescent, causing them to accumulate with age. Therefore, removing these cells has become a priority of the rejuvenation biotechnology industry.
As you age, increasing numbers of your cells enter into a state known as senescence. Senescent cells do not divide or support the tissues of which they are part; instead, they emit a range of potentially harmful chemical signals that encourage nearby healthy cells to enter the same senescent state. Their presence causes many problems: they reduce tissue repair, increase chronic inflammation, and can even eventually raise the risk of cancer and other age-related diseases.Senescent cells normally destroy themselves via a programmed process called apoptosis, and they are also removed by the immune system; however, the immune system weakens with age, and increasing numbers of senescent cells escape this process and begin to accumulate in all the tissues of the body.
By the time people reach old age, significant numbers of these senescent cells have built up, causing chronic inflammation and damage to surrounding cells and tissue. These senescent cells are widely considered a key player in the development of age-related diseases.
There appears to be a strong relationship between obesity and senescence. Reports like the ones described above suggest that obesity may promote the aging process by inducing senescence. Conversely, senescence and the resulting pro-inflammatory secretory phenotype could contribute to the morbidity associated with obesity and plays a role in the development of insulin resistance and diabetes. There is vast literature in support of this view, and we refer the interested readers to gather valuable in-depth reviews. Finally, Fontana et al. have proposed that caloric restriction might exert its anti-aging capacities by limiting senescent cell accumulation.
The researchers continue to review the literature and try to reach a conclusion for each hallmark of aging in relation to obesity, and we recommend reading the study. The paper makes a solid case for the harm that obesity causes, particularly in the context of aging and its acceleration.
The bottom line here is that, from the view of longevity, avoiding obesity and being overweight is a positive move; when combined with regular physical activity, a remedy for the former, the chances of living a healthier and longer life are increased.
With the arrival of rejuvenation therapies now becoming an increasingly plausible prospect in the coming decades, it would be wise to do everything you can to live long enough to benefit from these new technologies, this, by its nature, includes staying active and eating a balanced diet to avoid becoming obese.
 López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2013). The hallmarks of aging. Cell, 153(6), 1194-1217.