As scientists delve into the intricacies of longevity, they’re getting a better grasp on the nitty-gritty details of aging — what happens at the molecular and cellular levels. With this knowledge, they — and the rest of us — are hoping to gain insights into how we can delay and minimize the effects of aging, whether through lifestyle modifications, drugs or other therapy.
Processes at play
Aging involves several forces — actions within our bodies and environmental influences outside them. While there’s still much that we don’t know about why one individual ages relatively well and another has more difficulty, scientists and researchers are consistently gaining ground in their understanding of the fundamental biology of aging.
Some approaches to aging follow the line of thinking that cellular damage over time leads to the loss of normal functioning and the development of aging. Others are based on the idea that aging follows a programmed timetable — it has an upper limit.
No single theory or phenomenon appears to completely explain why aging occurs. Researchers generally view aging as many processes that interact with and impact each other. Here are some of the biological processes that appear to be at play.
One hallmark of aging that researchers readily agree on is genetic damage that occurs over time within the body’s cells. For many reasons, DNA, the body’s intricate blueprint for performing all of its functions, gradually becomes dam- aged. The body has several ways to repair DNA, but as the damage accumulates, genes, proteins and cells may malfunction, leading to disease and deterioration.
DNA damage can result from forces both within and outside the body. Sometimes, for example, when cells divide and multiply, errors occur in the DNA replication process within a cell and these changes are carried on to new cells, throwing off cellular function and communication within cells.
DNA damage can be especially impactful when it affects stem cells — the precursor cells that give rise to new, specialized cells for the regeneration of skin, digestive, brain and other organ tissues. Genetic damage in stem cells can cause them to stop functioning correctly and make tissue regeneration difficult.
Oxidative stress is another source of DNA damage. It results when cellular structures called mitochondria become damaged. Mitochondria are the cell’s powerhouses. They convert food into energy used by cells. During the conversion process, mitochondria produce unstable molecules called reactive oxygen species, better known as free radicals.
Usually, free radicals are kept in check by compounds called antioxidants, which can come from dietary nutrients such as vitamin E, vitamin A and beta carotene. However, lifestyle factors such as smoking, alcohol use, and an un- healthy diet can damage mitochondria and accelerate the production of free radicals, causing oxidative stress.
One of the effects of oxidative stress is deterioration of the endcaps of chromosomes (telomeres). Shortened telomeres are a key feature of aging cells. Telomeres typically get shorter each time a cell divides, but evidence suggests that oxidative stress may also play a role in this particular form of DNA damage.
External factors that can result in genetic damage include sun exposure, which harms skin cell DNA, and polluted air, which damages the DNA of lung cells. These forces can cause chemical alterations that interfere with the way genetic instructions are carried out, ultimately leading to the production of unhealthy cells that contribute to diseases such as skin cancer and lung disease.
Cellular clutter and decline
Your body’s genes encode proteins, converting them into forms that allow them to become the basic building blocks of all cells. Proteins can be expressed in many ways, which is why liver cells differ from heart cells — each has their unique function.
Protein regulation is an important part of cell maintenance. Autophagy is the name for the process your body uses to get rid of damaged or redundant cell proteins and parts. When this process doesn’t work as it should, cells can get cluttered with wonky proteins, which can affect DNA repair and normal cellular responses. Protein clutter or buildup is seen in age-related conditions such as Alzheimer’s disease, which is characterized by clumps of harmful beta-amyloid proteins.
Not only can cells become cluttered with proteins, but their internal structures may become altered. The “skeleton” of a cell (cytoskeleton) is made up of a microscopic network of protein filaments and tubules. Over time, this network becomes more rigid and fixed, so that a cell can’t flex and move as it once did, reducing intracellular communication and increasing risk of disease. For example, hardening of the cells that line your blood vessels can impede healthy blood flow and lead to high blood pressure.
Research suggests that when some cells within the body deteriorate — whether because of genetic damage, telomere erosion, oxidative stress, protein clutter or other reasons — the cells eventually stop dividing and enter what’s called a senescent state. Senescent cells aren’t dead, but they aren’t functioning appropriately, either. The cells are sometimes described as “Zombie cells.”
The body naturally removes many senescent cells but not all. Some linger and may harm neighboring cells — simi- lar to a piece of moldy fruit corrupting an entire fruit bowl. In older adults, senescent cells more readily accumulate and there’s mounting evidence linking these cells to age-related conditions such as osteoporosis, neurodegeneration and cardiovascular disease.
However, researchers have noticed that some conditions, such as obesity, are marked by the presence of senescent cells even among younger individuals. What this means is that it’s possible that senescent cells both contribute to and result from disease and aging.
Inflammation is part of the body’s natural defense process, designed to protect against external factors such as infections, toxins and trauma and to repair damage. When you cut your finger, the skin around the cut may swell and redden. That’s your body’s inflammatory response at work, activating a cascade of immune reactions that eliminate germs and repair injured cells.
Scientists have also discovered a less healing inflammatory response — a low-grade inflammation present throughout the body. This form of inflammation, sometimes called inflammaging, appears to be more prominent later in life and is closely associated with cellular senescence.
Low-grade chronic inflammation is thought to develop in response to things such as an unhealthy diet, too little exercise, ongoing levels of high stress and environmental pollutants, as well as underlying medical conditions, such as rheumatoid arthritis, diabetes, and obesity. Chronic inflammation also is linked to disturbances in the balance of microorganisms — bacteria, viruses, fungi — that populate the human gut (gut microbiome). The gut microbiome and how it affects many aspects of human health and longevity are ongoing areas of investigation.
From what you just read, it’s clear that researchers know more today than ever before about the aging process. Though there’s no manual yet for how to live forever, understanding the mechanics of aging can provide links to new ways of living well, well into old age.
Mayo Clinic on Healthy Aging
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