The Hallmarks of Aging and How to Get Started on Your Journey to a Longer, Healthier Life

There is no simple answer to why we age and how to stop it, as a multitude of factors ranging from genetic to lifestyle to environmental all play a significant role in the aging process. 

And our biological age is often different than our chronological age. As opposed to the chronological age that measures the number of years you’ve spent on the earth, biological age assesses damage and dysfunction to cellular markers—essentially, how fast your cells, organs, and tissues are aging. And while these two tend to line up during our younger years, as we grow older, they can drift further and further apart. 

With an accelerated biological clock, you’re more likely to experience accelerated aging and eariler onset or progression of age-related disorders. And although the aging that occurs on the outside (such as graying hair, wrinkles and loss of muscle tone) is often considered simply a vanity metric, it tends to mirror the aging occurring on the inside. On the flip side, maintaining healthy habits throughout life can keep you biologically young—and looking young—regardless of chronological age. Let’s take a closer look at the cellular causes of aging and how to get started on your journey to living a longer and healthier life. 

What Are the Causes of Aging? 

Quite obviously, aging is caused by getting older. But it’s not just another candle on your birthday cake that causes your cells, organs, and tissues to age—there are millions of unseen factors occurring in our bodies every day that either slow down or accelerate the aging process.

Longevity researchers often refer to the “Hallmarks of Aging” as the set of cellular factors that drive aging. These hallmarks were first described in a June 2013 paper published in Cell as a set of nine fundamental characteristics that define why our bodies and cells age, which were updated by the same authors in 2022 to now include 12 hallmarks. 

A hallmark of aging must meet three criteria: it arises during the normal aging process, it will accelerate aging when upregulated in experiments and it will decelerate, stop, or reverse aging when downregulated. 

As briefly as possible, the 12 hallmarks of aging are:

• Genomic instability: The accumulation of genetic damage throughout life that damages DNA and leads to errors in our genetic sequences. 

• Telomere attrition: Telomeres—protective structures at the ends of our chromosomes—shorten with every cell division to protect vital genetic information and are considered a proxy for measuring biological age. Once a cell reaches the end of its telomere, it can no longer replicate and becomes senescent. 

• Epigenetic alterations: The epigenome is a code that dictates which parts of the genome are expressed at certain times. With age, environmental exposures, or unhealthy lifestyle habits, the epigenome becomes less able to turn genes on or off correctly, leading to lost epigenetic information that contributes to aging. 

• Loss of proteostasis: Proteostasis, or protein homeostasis, maintains proteins in their correctly folded states. Loss of protein maintenance causes misfolded proteins that can’t function properly, thereby altering cellular function.

• Deregulated nutrient-sensing: Nutrient-sensing systems evolved to protect us during times of food scarcity. When nutrients are abundant, the body places focus on energy storage and reproduction, while nutrient scarcity allows the body to prioritize cellular repair and maintenance, including processes like autophagy. The main nutrient-sensing pathways are IIS (‘insulin and IGF-1 signaling’), sirtuins, mTOR, and AMPK.

• Mitochondrial dysfunction: Mitochondria are primarily responsible for energy production via ATP, but they also produce free radicals and reactive oxygen species. As mitochondrial function declines, we see reduced energy production and cellular turnover combined with increased free radical damage. 

• Cellular senescence: Senescent cells have stopped dividing but remain in the body, secreting inflammatory compounds that damage nearby tissues and cells. A buildup of senescent cells accelerates aging.

• Stem cell exhaustion: Stem cells are a blank canvas that can grow into any other cell type, which is necessary to repair and regenerate damaged tissues and other cells. Aging depletes the supply of healthy stem cells, causing disease, frailty, organ dysfunction, and low immune functioning. 

• Altered intercellular communication: Appropriate communication between cells is necessary to maintain the health and integrity of the tissues and organs. The aging body is more prone to dysfunctional communication, most often due to chronic and low-grade inflammation, senescence, free radical accumulation, and DNA damage. 

• Disabled macroautophagy: Autophagy is our cellular trash and recycling system that clears out dysfunctional or toxic cells, proteins, mitochondria, and other cell parts. Autophagic activity decreases with age, leading to a buildup of these damaged cells and organelles that contribute to aging and disease. 

• Chronic inflammation: Inflammation is both a cause and symptom of many of the other hallmarks of aging. Chronic release of pro-inflammatory compounds accelerates aging and disease, a process referred to as “inflammaging.” Chronic inflammation inhibits stem cell function, reduces the immune system’s ability to fight pathogens and drives the aging process. 

• Dysbiosis: Dysbiosis is a disruption to the gut microbiome, which plays an important role in health and longevity. Dysbiosis has been shown to affect not only longevity but also cardiovascular, cognitive, neurological, metabolic, immune and digestive health.  

How to Live a Longer, Healthier Life

While many of the 12 hallmarks of aging may sound like they are out of our control, our daily actions actually play a significant role in whether or not these processes occur. Even if you already experience signs of aging—whether external or internal, as measured by biological age tests—it’s not impossible to turn back the clock. 

Some of the lifestyle and environmental factors that can help you lead a longer and healthier life include: 

• Not smoking. Although we certainly see fewer people smoking today than in the 90s and 2000s, 12.5% of U.S. adults were still current smokers in 2020. Smoking remains the leading cause of preventable disease, disability and death, as it increases genomic instability, DNA damage, epigenetic alterations, telomere attrition, and many more hallmarks of aging.

• Maintaining a healthy weight. Higher BMI is linked to increased biological age, as being obese accelerates age-related epigenetic changes, inflammation, oxidative stress and DNA damage. Being obese is also associated with most, if not all, chronic conditions, leading to reduced healthspans. 

• Healthy mood. Chronic depressive symptoms are linked to increased epigenetic aging, which can reduce healthspan and lifespan. Talk to your healthcare provider about therapies, medication or lifestyle changes to help with mood. 

• Minimize alcohol consumption. Alcohol accelerates biological aging, especially when consumed chronically and in excess. Research shows that drinking 29 units of alcohol per week (about ten glasses of wine) accelerated telomere shortening at a rate equivalent to up to three years of aging. Moderate alcohol consumption is one drink per day for women and two for men—but in this case, less is definitely better.  

• Consume dietary antioxidants. From alpha-carotene to zeaxanthin, plant-based compounds called polyphenols act as antioxidants and fight oxidative stress in the body to protect DNA and slow aging. Some antioxidants and the foods they’re found in include resveratrol (red grapes and wine), curcumin (turmeric), quercetin (apples and onions), anthocyanins (berries), sulforaphane (broccoli), ellagic acid (berries and pomegranate) and catechins (green tea and cocoa). Antioxidant supplements like trans-resveratrol, spermidine, pterostilbene, fisetin, green tea extract (EGCG), and hydroxytyrosol can also help to bridge the gap. 

• Support NAD+ levels. NAD+ (nicotinamide adenine dinucleotide) is a compound known as a coenzyme, meaning it helps other enzymes function correctly. This vital molecule is needed by virtually every cell in our bodies, aiding hundreds of processes ranging from brain cell growth to repairing DNA to assisting mitochondrial function. NAD+ plays a critical role in maintaining cellular and metabolic functions, which translates to better health and longevity of our cells, organs and bodies. Although NAD+ levels are known to decline as we grow older, you can support your NAD+ levels by adding NAD+ precursors like NMN (nicotinamide mononucleotide) or NR (nicotinamide riboside).

• Up your omega-3s. Consumption of omega-3-rich fatty fish, like sardines, salmon and mackerel, is linked to improved health outcomes and longer telomeres.

• Exercise. Regular exercise—both aerobic and resistance training—can slow down aging on the cellular level. It also promotes better organ function, contributing to longer healthspans. Exercise maintains genomic stability, telomere length, proteostasis, nutrient sensing, and mitochondrial function. Research shows that adults with high physical activity levels have telomeres that are nine years younger than those who are sedentary. 

• Train your brain. In addition to cardiovascular and strength exercises, training your brain can increase neuroplasticity—the ability to adapt and strengthen neural connections. Brain training activities include puzzles, word games, chess, learning a new language or skill, and even some video games. 

• Healthy sleep schedule. Sleep is essential for autophagy, clearing out toxic brain waste and other cellular “housekeeping,” processing information, forming new neural pathways, strengthening immune function and much more. Research shows that adults who get enough sleep (ideally seven to nine hours a night) have longer telomeres. 

• Foster a community. Being lonely can accelerate aging by 1.65 years, and fostering a strong sense of community through family, friends, neighbors or social groups can significantly boost both mood and health. 

Overall, the things we do—or don’t do—every day become our habits, which become our lives. Although not every day has to be a perfect representation of health, people who consistently maintain healthy habits, like exercising, socializing, eating antioxidants and getting good sleep, are more likely to lead long, healthy lives.

References: 

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Han LKM, Aghajani M, Clark SL, et al. Epigenetic Aging in Major Depressive Disorder. Am J Psychiatry. 2018;175(8):774-782. doi:10.1176/appi.ajp.2018.17060595

Jackowska M, Hamer M, Carvalho LA, Erusalimsky JD, Butcher L, Steptoe A. Short sleep duration is associated with shorter telomere length in healthy men: findings from the Whitehall II cohort study. PLoS One. 2012;7(10):e47292. doi:10.1371/journal.pone.0047292

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