The Genetics of Age-Related Physical Function Impairment

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The Genetics of Age-Related Physical Function Impairment

Date of Content: May 11, 2024
Written by: Harvey Talento
Reviewed by: Maarit Tiirikainen, PhD


What is Age-Related Physical Function Impairment?

Age-related physical function impairment is a common phenomenon observed in older adults, characterized by a decline in physical capabilities and an increased risk of chronic diseases, falls, and functional limitations. This impairment is often associated with a sedentary lifestyle, which can further exacerbate the decline in physical function and increase the risk of mobility disability, frailty, and loss of independence.

Prevalence and Characteristics

The prevalence of physical function impairment increases with age, with approximately 22.9% of older adults aged 60-69 years and 42.9% of those aged 80 years and older reporting functional limitations. Women are more likely to experience age-related physical function impairment, and the majority of those affected have a body mass index (BMI) above the normal range. Additionally, about 80% of adults aged 60 years and older have at least one chronic condition, and 77% have at least two, which can contribute to the decline in physical function.

Age-related physical function impairment

Impact on Healthcare and Quality of Life

Older adults with lower levels of physical function generally face higher healthcare costs. Several factors contribute to this:

  • Chronic diseases: These are common among older adults and account for 75% of healthcare spending in the United States.
  • Low physical function and sedentary lifestyle: This combination increases the risk of functional decline, disability, and mortality.

As individuals age, there is a natural decline in physical function, including aerobic capacities, muscle strength, flexibility, speed, and balance, which can lead to difficulties in carrying out activities of daily living (ADL). This decline in functional capacity is a strong predictor of negative events and can result in a loss of autonomy, reduced quality of life, and compromised well-being.

The combination of low physical function and a sedentary lifestyle, which is prevalent among older adults, can impair mobility, creating a cycle of deconditioning that accelerates the loss of independence and increases the need for healthcare services and associated costs. Physical inactivity exacerbates the deterioration in functional abilities observed with age, further emphasizing the importance of physical activity in maintaining physical function and preventing functional decline in older adults.

Moreover, age-related physical function impairment can lead to mobility problems, changes in gait speed, and an increased risk of falls, which are early indicators of physical health decline and functional disability in older adults. A decline in cardiorespiratory fitness, strength, or balance can limit an individual’s functional reserve, making everyday activities more challenging and potentially leading to dependency and frailty. Additionally, deficits in physical function have been associated with an elevated risk of falls, diminished ability to live independently, and poorer self-reported health.

How Genetics May Influence Age-Related Physical Function Impairment

The decline in physical function with age is a multifaceted process influenced by various factors, including genetics. Two genes that, have been studied for their roles in age-related physical function impairment, ACTN3, and UCP2, are discussed below

ACTN3 and Physical Performance

The ACTN3 gene, particularly the R577X (rs1815739 C>T) polymorphism, is notable for its impact on muscle function. Research indicates that this gene variant can significantly affect physical performance and frailty in older adults. A study involving an older Chinese population found that the XX (TT)and RX (CT) genotypes of the ACTN3 R577X polymorphism were linked to variations in physical performance and frailty scores. For instance, men aged 70-79 with the 577X (T) allele showed slower 5-meter walk times, reduced grip strength, and longer times in the Timed Up and Go test. Women in the same age group with the 577X allele exhibited higher frailty index scores.

Similarly, a study in Japan demonstrated that the ACTN3 R577X genotype influenced lower-extremity muscle function. Men aged 55 and older with the XX genotype (rs1815739-TT) performed worse in the chair stand test compared to those with the RR or RX genotypes, indicating that the 577X polymorphism may impair physical function, particularly in lower body muscle performance.

UCP2 and Baseline Functional Performance

The UCP2 gene, specifically the G866A (rs659366 G>A) polymorphism, has also been linked to physical function in older adults. UCP2 is involved in regulating energy metabolism, which can affect muscle performance. A study examining Caucasian older adults found that the UCP2 G866A genotype correlated with baseline measures of physical performance. Those with the GG genotype had slower 8-foot Up-and-go times compared to GA or AA genotypes. Moreover, after a 12-week exercise program, individuals with the GG genotype showed greater improvements in their 8-foot Up-and-go times than those with the GA or AA genotypes, suggesting a genotype-specific response to exercise interventions.

Non-Genetic Factors Influencing Age-Related Physical Function Impairment

Beyond genetics, several lifestyle and environmental factors contribute to age-related physical function impairment. These include:

      • Low physical activity: Lack of regular exercise can lead to muscle weakness, poor cardiovascular health, and decreased mobility.
      • Poor diet: Inadequate nutrition can result in deficiencies that affect muscle and bone health, energy levels, and overall physical function.
      • Obesity: Excess body weight places additional strain on joints and muscles, leading to decreased mobility and increased risk of chronic diseases.
      • Smoking: Smoking damages lung function and cardiovascular health, reducing physical endurance and increasing the risk of respiratory diseases.
    • Sex: Men and women may experience different patterns of physical decline due to hormonal differences and other biological factors.
    • Cognitive impairment: Declines in cognitive function can affect coordination, balance, and the ability to perform daily activities.
    • Depression: Mental health issues can reduce motivation for physical activity and self-care, leading to poorer physical health.
    • Multiple chronic diseases: Conditions such as diabetes, heart disease, and arthritis can compound physical limitations and impair function.

Prevention Strategies for Age-Related Physical Function Impairment

Maintaining physical function as we age requires a holistic approach that includes lifestyle adjustments, dietary considerations, and regular health check-ups. Here are several effective strategies:

Natural Light Exposure

Regular exposure to natural light is crucial for maintaining healthy circadian rhythms, which regulate sleep patterns and overall energy levels. Good sleep quality enhances mood and motivation, which is essential for engaging in physical activities. Aim for at least 20-30 minutes of natural light exposure each day, preferably in the morning.

Auditory Stimulation

Engaging in activities that require auditory processing, such as listening to music or participating in conversations, supports cognitive function and coordination. These activities can indirectly benefit physical function by enhancing brain health, which is linked to better motor control and reduced risk of falls.

Tactile Engagement

Incorporating tactile activities, such as gardening, crafts, or massage, can improve sensory integration and motor skills. These activities stimulate different sensory pathways and promote fine motor skills and hand-eye coordination, which are vital for daily tasks and overall physical function.

Active Recovery

Active recovery involves incorporating light activities and mobility exercises on rest days. This strategy promotes circulation, reduces stiffness, and aids in muscle recovery. Gentle activities like walking, stretching, or yoga can help maintain flexibility and prevent muscle soreness.

Nutritional Support for Recovery

Nutrition plays a critical role in muscle and joint recovery. Focus on nutrients such as protein, vitamin C, omega-3 fatty acids, and antioxidants. These nutrients support tissue repair, reduce inflammation, and promote overall joint health. Include a variety of fruits, vegetables, lean proteins, and healthy fats in your diet.

Rest and Sleep

Adequate rest, including quality sleep, is essential for physical and neural recovery. Ensure you get 7-9 hours of sleep each night to allow your body to repair and rejuvenate. Establish a regular sleep routine and create a sleep-friendly environment to enhance sleep quality.

Protein Intake

As we age, our protein needs increase to support muscle repair and growth. Aim for high-quality protein sources such as lean meats, legumes, and dairy products. Consider incorporating protein-rich snacks and meals throughout the day to meet your dietary needs.

Anti-inflammatory Foods

Incorporate anti-inflammatory foods into your diet to support joint health and reduce inflammation. Foods rich in omega-3 fatty acids (such as fatty fish), antioxidants (like berries and leafy greens), and phytonutrients (found in a variety of colorful fruits and vegetables) can help combat chronic inflammation.


Proper hydration is vital for overall health, including maintaining kidney function and joint lubrication. Drink plenty of water throughout the day to stay hydrated, especially during and after physical activities. Proper hydration supports physical performance and reduces the risk of dehydration-related issues.

Regular Health Screenings

Regular health screenings are important for early detection and management of conditions that can impair physical function, such as osteoporosis or arthritis. Stay proactive with annual check-ups and follow your healthcare provider’s recommendations for screening tests. Early intervention can prevent or mitigate the progression of these conditions.

Implementing these strategies can help maintain physical function, enhance quality of life, and support healthy aging. By combining lifestyle adjustments, nutritional support, and regular health monitoring, you can effectively combat age-related physical function impairment.

How to Prevent Vascular Aging

There are several strategies to prevent or delay vascular aging:

Lifestyle Modifications

  • Diet: A healthy diet low in processed foods, unhealthy carbohydrates, and saturated fats can help prevent vascular aging by reducing inflammation and oxidative stress. Foods like olive oil and its extracts have been shown to have anti-vascular aging effects.

Pharmacological Interventions

Certain drugs and supplements may help prevent vascular aging:

  • Dietary supplements, including resveratrol, COQ10, and folate, have shown promise in reducing biomarkers of aging and maintaining arterial function. 
  • Senolytics and senomorphics target specific signaling pathways (like PI3K/Akt, SASP, eNOS, ATM/ATR, and oxidative stress) and may have anti-vascular aging effects.

The best evidence-based strategies to prevent vascular aging include regular aerobic exercise, a nutritious and healthy diet, and maintaining a healthy weight. Pharmacological interventions and novel lifestyle approaches may provide alternatives for those unable to adhere to conventional healthy behaviors.

About the LifeDNA Aging Report

Unlock the secrets of your aging process with the LifeDNA Aging Report, a premium resource that provides personalized insights into age-related physical function impairment. By analyzing your unique genetic makeup, this comprehensive report offers invaluable information on how specific genes and their variants, such as genes ACTN3 and UCP2, may influence your physical capabilities as you age. With actionable recommendations tailored to your genetic profile, you can proactively address potential risk factors and optimize your lifestyle to maintain optimal physical function.

Get your report today!


  • Age-related physical function impairment entails a decline in physical capabilities and an increased risk of chronic diseases, falls, and functional limitations.
  • The prevalence of physical function impairment rises with age, affecting approximately 22.9% of older adults aged 60-69 years and 42.9% of those aged 80 years and older.
  • Chronic diseases and sedentary lifestyles contribute significantly to physical function impairment, leading to higher healthcare costs.
  • Genetics, including genes like ACTN3 and UCP2, play a role in age-related physical function impairment.
  • The ACTN3 R577X polymorphism influences muscle function and physical performance in older adults.
  • The UCP2 G866A polymorphism is associated with baseline measures of physical performance and may respond differently to exercise interventions.
  • Lifestyle factors such as low physical activity, poor diet, obesity, and smoking contribute to physical function impairment.
  • Other influencing factors include sex, cognitive impairment, depression, and the presence of multiple chronic diseases.
  • Prevention strategies for age-related physical function impairment include natural light exposure, auditory stimulation, tactile engagement, active recovery, nutritional support, rest and sleep, adequate protein intake, consuming anti-inflammatory foods, hydration, and regular health screenings.



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