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What Happens When We Age: The Biology of Aging

We’re all familiar with the most visible signs of aging. Gray hairs pop up. Bald spots make themselves known. Fine lines — or deep wrinkles — appear out of nowhere. Suddenly you (and everyone your age) start squinting to read menus, labels, books…print that previously had not been a problem. Over time, physique changes: the loss of muscle and bone intensify, along with functional declines in muscle tone, strength, posture, balance, speed and agility. Joint aches and pains may come and go. Waistlines expand — which almost always stems from an increase in belly fat, particularly in deep visceral fat packed around the organs. This ab fat indicates worsening metabolic health, signaling higher risks for type 2 diabetes, poor cholesterol levels, high blood pressure and heart disease, all conditions associated with age.1

Biology of aging

Why does the body break down? There are many reasons for age-related physiological decline. “To put it very simply, wear and tear eventually outrun our repair mechanisms,” explains Jim Mellon, co-author of Juvenescence: Investing in the Age of Longevity.2 What tips the scale is often a person’s lifestyle habits. Unhealthy living with poor diet and not enough exercise or sleep can trigger cells to poop out faster. As dysfunctional cells accumulate, tissues and organs or organ systems are affected and body breakdown accelerates. Then voila! Those droops, sags, spots and bags associated with aging appear — along with other health conditions that signal deteriorating health.

But aging poorly isn’t a done deal and recent scientific advances are providing new insights in how to mitigate growing old. Here, three things that happen when you age and possible healthy-aging fixes.

Inflammation becomes chronic

What affects one area of the body can affect another. This complexity stems from the way the body is structured; it’s organized into a hierarchy of different levels, from biochemical reactions within individual cells, to tissues, organs, organ systems, and finally the entire organism.3 Wear and tear from aging can be seen from the cells on up. Dysfunction at each level can influence surrounding cells, tissues, organs and systems. This may help explain why the physiological process of aging can have such widespread effects.

Inflammation, for example, is a condition associated with aging. Inflammation occurs from a hyped-up immune response that can lead to swelling, pain and loss of function in cells and tissues. For immediate responses to an invader, irritant or injury, inflammation can be protective and help the body heal. But if prolonged, this hypersensitive-state can trigger continued immune responses that stress, rather than help.4 “Chronic inflammation has long been recognized as a contributing factor to a litany of age-related conditions like obesity, metabolic disease, cardiovascular disease, and dementia,” says Gregory Bailey, MD, a physician and CEO of Juvenescence. “Some eminent scientists believe that inflammation is a major driver of aging and that older, senescent cells may be responsible for chronic pro-aging inflammation.” Good health relies on the body’s ability to repair and rebuild its tissues and to generate healthy immune responses. Tissue rejuvenation comes from the power of cells to divide and multiply. If this system is impaired, the body deteriorates. Cellular senescence is a state where cells go quiet. But they don’t die: they stop multiplying, but they hang around, releasing a host of compounds that can affect other cells and tissues, spreading inflammation.

“If immune cells can’t fully challenge infectious pathogens or other foreign bodies and also may mistarget cellular waste products that it cannot destroy, the body is vulnerable to illnesses and the persistent inflammation known as inflammaging sets in,” says Dr. Bailey.

Family cooking together

Preventing chronic inflammation

Consuming a healthy diet filled with whole plant foods is anti-inflammatory. Plant foods contain antioxidants such as Vitamin C, selenium, Vitamin E and a host of phytochemicals that can quench the free radicals that create inflammation and can also provide fiber to feed the microbiome. The microbiome refers to the microorganisms, especially in the gut, that exert systemic effects all over the body. Fiber is their preferential fuel and sufficient quantities allow beneficial bacteria to flourish and produce beneficial compounds like short chain fatty acids.5 A poor diet, especially one high in animal foods that contains choline and L-carnitine and is low in fiber, allows more harmful bacteria to thrive that then produce a compound called trimethylamineoxide (TMAO). TMAO contributes to inflammation in the body, especially in blood vessel walls and is thought to be a major contributor to heart disease.6 Foods containing omega 3 fatty acids such as chia seeds and fish have been shown to be anti-inflammatory, as have certain compounds in herbs and spices including curcumin found in turmeric. Dietary supplements containing these compounds may help.7

Blood measures of inflammation include c-reactive protein (CRP) and cytokines such as interleukins (IL-6) and tumor necrosis factor (TNF-a).8 Nonsteroidal anti-inflammatory drugs (NSAIDs), as well as steroids, have been used to reduce inflammation, although both have been associated with unwanted side-effects. “A number of companies are working on other therapeutics, like senolytics, to reduce those bad actors that contribute to a chronic inflammatory state,” says Dr. Bailey. “This class of drug can remove old and damaged, or senescent cells.”

Hormones go awry

Hormones are messenger chemicals in the body produced by glands like the thyroid, or organs that act like glands such as the pancreas. These chemicals that are part of the body’s endocrine system produce powerful effects. Insulin helps regulate blood sugar; growth hormone plays a role in the development of muscle and bone. Estrogen and testosterone not only influence sexual function and libido in men and women, but they can affect fat mass, strength and bone density.9

As hormone levels change with aging, functions associated with each hormone decline. And since many endocrine functions are intertwined, adverse effects in one will adversely affect the other, according to a review in the journal, Clinical Chemistry.10 Some of the physiological changes that result from hormone shifts, like the loss of muscle mass and bone, affect body shape and function, leading to poor posture, poor gait, unsteadiness and weakness. Risks increase for osteoporosis and sarcopenia, as well as for life-threatening hip fractures. Drops in estrogen, can lead to the accumulation of belly fat which increases the risk for metabolic conditions such as hypertension, type 2 diabetes and cardiovascular disease.11

How can hormone levels be helped?

Hormone replacements have long been used as an anti-aging strategy, and they can help ameliorate symptoms. “But their use is controversial,” says Dr. Bailey. That’s because while there may be benefits and previous hormone functions can be restored, using them is not without risks. For example, supplementing with growth hormone can reduce body fat, increase muscle mass, strength and bone. But prescribing it is illegal if a person has not been diagnosed with abnormally low blood levels of the hormone because of its risks. Treatment with growth hormone can increase the risk of body fat, insulin resistance and high blood glucose levels and has been linked to higher mortality rates.12

Hormone replacement therapy in women, designed to replace the estrogen and progesterone loss with menopause, can improve symptoms like vaginal atrophy, hot flashes, and can slow bone loss — but with a concurrent increased risk in breast cancer, stroke and cardiovascular disease.13 Testosterone supplementation in men can restore lean body mass, strength and libido, but there have been concerns that its use may increase the risk of heart disease, although studies are mixed.14,15

While hormones can’t necessarily be manufactured or levels restored simply by following a healthy diet with regular exercise, there is some evidence that exercise, especially resistance training with weights and high intensity interval training can elevate sex hormones in men. Many studies have seen transient boosts in testosterone from both high intensity aerobic exercise and resistance training with heavy weights.16,17 But the effect is temporary and it’s unclear if, over time, an acute boost following a workout translates into hormone levels that are higher overall.

One randomized controlled trial in the journal Medicine & Science in Sports & Exercise had 102 previously sedentary men workout for one year. They did four hours a week of structured aerobic exercise along with another two hours per week of moderate-to-vigorous physical activity, like playing basketball. While there were no significant differences between the exercisers and control group in a number of hormone levels including testosterone and free testosterone, there were statistically significant increases in dihydrotestosterone (DHT) which is converted from testosterone and considered to be a more biologically active androgen, and sex-hormone binding globulin (SHBG). Both are hormones that at higher levels are associated with improved health, including with less insulin resistance.18

There is promise that therapeutics may be able to help balance some of the hormone dysregulation that accompanies aging. “Much work is being done investigating the use of stem cells to regenerate pancreatic beta cells, for example” says Dr. Bailey. With more functioning cells, the pancreas would then be able to rev up its production of insulin. Early studies are exploring the use of different types of stem cells to regenerate cells in the adrenal and thyroid glands, as well as in the testes and ovaries.19

Cell activity deteriorates

The conventional wisdom is that people get sick. Then, over time health worsens as a variety of unrelated chronic and/or debilitating health conditions manifest. A person gets high blood pressure. Later he or she develops diabetes. After that, signs of gout emerge, and so on.

Many people assume that their fate of developing specific health conditions is dictated by their genes. In a few cases, this can be true. DNA in genes acts as a blueprint for cells to follow to perform their individual functions. But disease-related genes are not always expressed. In other words, just because you have genes that predispose you to certain conditions, doesn’t mean you will get the condition.

The fundamental ways in which our cells work are now being examined to understand how we might slow, stop, or even reverse the aging process

Dr. Greg Bailey, MD
Chief Executive Officer, Juvenescence

Genes can be damaged, though, from exposure to external stimuli like air pollution, radiation from the sun or chemicals in the environment or internal stimuli such as free radicals, pathogens or chemicals that have been ingested. Even though cells are supposed to be able to repair and rebuild, with aging the process is less robust. As damage accumulates, body systems can be impaired and manifest in the symptoms and diseases of aging.

The new thinking is that aging is itself the main disease. The breakdown of the body and related co-morbidities are its symptoms. The field of geroscience considers the presence of multiple health conditions and diseases to be a multisystem expression of an advanced stage of aging, rather than simply a coincidence of random diseases that happen to occur at the same time, according to a review in the journal Nature.20

“I believe that aging is a unitary disease state that compromises our cells’ natural abilities to sustain themselves, or to regenerate,” says Dr. Bailey.

The fact that, at the most basic level, cells themselves—and their DNA—start to malfunction lends credence to the idea. Throughout life, all cells—including hair follicles, skin cells and muscle fibers—go through apoptosis: they are programmed to die. Through the process of autophagy, old, damaged cells are discarded, clearing the way for new cells to replace them. This allows tissues to undergo a sort of constant recycling. In the disease of aging, cells and tissues start to rejuvenate more slowly with time. And with aging, rates of apoptosis may overtake the production of new cells causing tissue degradation. At the same time, other senescent cells that are in a latent, but potentially toxic, state can accumulate and wreak havoc. The effects are felt in tissues, organs, organ systems and, finally, the whole organism.

Can aging cells be fixed?

A number of mechanisms which accelerate aging and related diseases, called the hallmarks of aging, have been identified. “The fundamental ways in which our cells work are now being examined to understand how we might slow, stop, or even reverse the aging process,” says Dr. Bailey. Improving behaviors by not smoking, exercising regularly and eating a healthful whole plant-rich diet can most certainly arrest some aspects of aging. But a number of therapeutics targeting the multiple pathways are being developed that may be as, or more, powerful. Those that show promise to delay aging and increase lifespan include rapamycin, acarbose, aspirin, metformin, sirtuin activators and others.20 “The science of discovering these solutions is still in its infancy, but on the horizon is a world is where drugs, genetic engineering, cellular enhancements and organ replacements, amongst other interventions, will add decades to our potential lifespan,” says Bailey.