Common diseases related to aging

Highlights

• The common mechanisms shared by aging and aging-related diseases/geriatric syndromes are called the hallmarks of aging
• The most common age-related diseases are cardiovascular disease, neurodegenerative diseases, cancer, and diabetes
• Geriatric syndromes include vision and hearing loss, frailty, and falls
  

Introduction

Aging is a driving factor of age-related diseases, including neurodegenerative diseases, cardiovascular diseases, cancer, immune system disorders, and disorders of muscles and skeleton. According to WHO, the most frequent illnesses connected with aging are hearing and vision impairment, osteoarthritis, diabetes, cardiovascular disease, depression, and dementia, often coexisting. Age-related occurrence of two or more chronic conditions is called multimorbidity, and it often leads to a vicious circle of illness. For example, disease such as diabetes impacts the health of the heart which in return influences the condition of lungs. Aging is also responsible for developing complex health states known as geriatric syndromes, e.g., frailty, urinary incontinence, or falls. These age-related diseases lead to a severe economic and psychological concern for patients, their families, and society (1).

Aging and disease: the commonalities and differences

The relationship between aging and aging-related diseases is complex because they share the basic mechanisms. The common mechanisms shared by aging and aging-related diseases/geriatric syndromes are called the hallmarks of aging. These are:

1. telomere attrition
2. genomic instability
3. mitochondrial dysfunction
4. cellular senescence
5. stem cell exhaustion
6. loss of proteostasis
7. deregulated nutrient sensing
8. epigenetic alterations
9. altered intercellular communication
   

Most chronic diseases are at least partially determined by one or more of these mechanisms (2). The main difference between aging and diseases lies in the speed and intensity of these nine aging cellular and molecular processes, combined with the specific genetics of an organ or system and the lifestyle, habits, and individual predisposition. All hallmarks of aging are progressing during life, leading to loss of homeostatic equilibrium of the organism (ability to regulate to internal conditions), lowering of reserve capacity (resources for responding effectively to stresses), and physiological decline that eventually can lead to metabolic syndrome and clinical diseases (1, 3, 4).

Cardiovascular disease

Cardiovascular disease (CVD) describes conditions affecting the heart or blood vessels. It is the primary cause of death and disability in the elderly population. The normal aging process is associated with progressive deterioration in the structure and function of the heart and veins. These age-related changes likely act as both a catalyst and accelerator in developing CVDs such as coronary heart disease, atherosclerosis, hypertension, myocardial infarction, and stroke (5). By 2030 CVD will be responsible for 40 % of all deaths. Aging leads to pathological alterations in cardiovascular tissues, such as hypertrophy or endothelial dysfunction (1). The most common cause of CVD is the life-long process of atherosclerosis (buildup of fats and other substances in and on the artery walls) which manifests itself clinically after decades, mainly as coronary heart or cerebrovascular or peripheral arterial disease (6). The underlying initiating factors of atherosclerosis are numerous, such as lipid unbalance, pro-inflammatory cytokines, or infections (6). Atherosclerosis is identified as a chronic inflammatory condition, and atherosclerotic plaques present cellular senescence (7). Coronary heart disease is a serious cause of morbidity and mortality in the elderly, as 82 % of patients who die of this disease are 65 years of age or older (5).  Hypertension or high blood pressure is another major contributor to atherosclerosis and the most common chronic disease of older adults, with a prevalence above 20 % in the general population. It is correlated with an increased risk of stroke, myocardial infarction, and heart failure. Numerous clinical trials have shown that reductions in blood pressure reduce the incidence of both stroke and myocardial infarction (8, 9).

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Neurodegenerative diseases

Aging is the most known risk factor for neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). Both AD and PD frequently have a long prodromal phase when the patient's memory starts deteriorating, but the person still is fully independent. Next is the clinical manifestation with a consecutive stage of progression leading to memory impairment, orientation problems, and difficulties in performing basic functions. AD and PD have another feature in common: deposits of improperly folded modified proteins, which can be detected in specific areas of the brain. Neurodegeneration processes of AD and PD are generally accompanied by neuroinflammation (3). AD is responsible for 70 % of all dementia cases, and it is the most prevalent neurodegenerative disease in the world. The frequency of AD rises with advancing age, doubling every five to ten years. It affects around 25 million people worldwide (10). The prevalence of Parkinson's disease increases with age, approximately ten times, between 50 and 80 years of age (1). PD is the second-most common neurodegenerative disorder that impacts 2–3% of the population above 65 years of age (11).

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Cancer

Cancer develops because certain cells begin to grow and divide uncontrollably and spread to other parts of the organism. The occurrence of most cancers increases with age, rising more rapidly after 45 years of age (12). It is estimated that from 2010 to 2030 in the US only, aging will lead to a 67 % increase in cancer incidence among people older than 65. Cancer is recognized as the second leading cause of death in elders. Life expectancy is quite variable in elderly cancer patients, based on comorbidities and other factors. One in two people is likely to develop malignant tumors in their lifetime. Possible reasons for this age-related increase of cancer are exposure to environmental toxins, declining immune system, and less effective DNA repair mechanisms. Inflammation is involved at different stages of tumor development and affects immune response and responses to therapy. Due to producing pro-inflammatory cytokines, prolonged inflammation may be directly or indirectly connected with oncogenesis (7).

Type 2 diabetes

Aging populations become more overweight which leads to increased rates of diabetes. It is estimated that the prevalence of diabetes among American older adults may increase more than 400 % by 2050. The disease itself is a complex metabolic disorder that affects the glucose levels in the body and is connected with chronic inflammation (13). Diabetes is a significant risk factor for CVD and is contributing to diabetic foot ulcers and amputations (9). Chronic diabetes damages blood vessels in the whole organism, including the eyes, which leads to diabetic retinopathy that can cause blindness (14). Both diabetes and hypertension have been connected with low grip strength, muscle strength and tone loss, and slower gait. Moreover, in patients with type 2 diabetes, the incidence of sarcopenia has been reported to be 15 % (15).

Immune system diseases

Due to aging, the immune system changes dramatically, which could cause the body to lose its ability to fight against infection or cancer and increase the risk of autoimmune diseases (1). The development of low-grade systemic inflammation, also called 'inflammaging' characterized by lifted serum C-reactive protein (CRP), is easily measurable (16). With age, the decline in B cell function and decline in T cell generation is observed together with altered T cell activation, and dysfunction of innate immunity. These changes decrease the body's capacity to fight infection and lead to, e.g., influenza, herpes zoster, and cytomegalovirus infections becoming more common and more severe in older adults while the vaccine is less effective. Chronically slowed inflammatory processes also slow down wound healing in older adults and cause higher risk of pressure ulcers (9, 16).
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Musculoskeletal disorders

Elders are prone to injuries and degenerative musculoskeletal disorders due to the muscle mass and strength decline and by the age of 85, approximately 20 % of people meet the criteria for sarcopenia – a significant loss of muscle mass and strength (9). Sarcopenia and osteoarthritis are among the most common aging-related musculoskeletal disorders and have a significant economic impact. Skeletal muscle mass and function decline by 30–50 % by age 80, especially amongst the elderly who are inactive. Increased inflammation leads to reactive oxygen species generation in skeletal muscles, which accelerates cell apoptosis and affects skeletal muscle catabolism. Also, defective mitochondrial function and weakened antioxidant defenses are associated with sarcopenia development (1). Sarcopenia-related conditions are also associated with the development of diabetes-related foot disease (15). Osteopenia is a typical loss of bone density connected with aging. Many elderly adults have osteoporosis, a more severe weakening of bone density, and falls are associated with an increased rate of bone fractures amongst elders (9).

Geriatric syndromes

·         Hearing and vision loss

Aging-related hearing loss due to inner and middle ear changes, loss of hair cells and increased ear wax production contributes to difficulty hearing. The prevalence of hearing loss increases due to age and accumulating risk factors and has a high association with reduced quality of life. Hearing loss is often linked to increased social isolation, leading to depression, cognitive decline, and reduced quality of life (9). In the case of vision loss, epidemiological studies clarify that eye diseases and vision loss are much more common in older adults than in younger age groups. In return, aging can impact our ability to perform typical everyday visual tasks such as recognizing objects, reading, engaging in mobility activities, thus influencing the quality of our life and well-being (17).

·         Frailty

Frailty can be defined as a particular vulnerability to stressors exhibited by weakness, slowness, exhaustion, and weight loss. Frailty status can be assessed quickly, and the frail state predicts future disability, falls, hospitalizations, and poor surgical outcomes (9). The causes of frailty are complex and based on genetic, biological, physical, psychological, social, and environmental factors. Frailty, in general, describes a physical and functional decline that may occur due to certain diseases, but interestingly also in the absence of identifiable specific diseases. Thus, frailty is viewed as a physiologic loss of reserves and resilience (18).

·         Falls

Falls are a significant cause of morbidity and disability among older adults. It is estimated that 30–40% of adults over age 70 fall each year, and rates are exceptionally high for older adults in long-term care facilities. Falls cause more than half of injuries among older adults and death rates associated with falls are higher for adults over age 85 than for other age groups (9). Falls are more prevalent due to sarcopenia and loss of motor function and become dangerous due to osteoporosis and slower healing.

Diseases most often come together

62 % of Americans over 65 have more than one chronic condition, and the prevalence of multiple chronic conditions is increasing due to population aging and rising diabetes rates. Older adults with multimorbidity account for a large percentage of health spending and the problem of polypharmacy (9). That is why preventive and restorative interventions instead of separate disease treatment should be the most crucial part of every medical check-up. Treatment of one age-related disease should always go in pair with other illnesses diagnostics.

References

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8.            Nabel EG. Cardiovascular disease. N Engl J Med. 2003;349(1):60-72.

9.            Jaul E, Barron J. Age-Related Diseases and Clinical and Public Health Implications for the 85 Years Old and Over Population. Front Public Health. 2017;5:335.

10.          Castellani RJ, Rolston RK, Smith MA. Alzheimer disease. Dis Mon. 2010;56(9):484-546.

11.          Poewe W, Seppi K, Tanner CM, Halliday GM, Brundin P, Volkmann J, et al. Parkinson disease. Nat Rev Dis Primers. 2017;3:17013.

12.          White MC, Holman DM, Boehm JE, Peipins LA, Grossman M, Henley SJ. Age and cancer risk: a potentially modifiable relationship. Am J Prev Med. 2014;46(3 Suppl 1):S7-S15.

13.          Tsalamandris S, Antonopoulos AS, Oikonomou E, Papamikroulis GA, Vogiatzi G, Papaioannou S, et al. The Role of Inflammation in Diabetes: Current Concepts and Future Perspectives. Eur Cardiol. 2019;14(1):50-9.

14.          Leley SP, Ciulla TA, Bhatwadekar AD. Diabetic Retinopathy in the Aging Population: A Perspective of Pathogenesis and Treatment. Clin Interv Aging. 2021;16:1367-78.

15.          Sable-Morita S, Okura M, Tanikawa T, Kawashima S, Tokuda H, Arai H. Associations between diabetes-related foot disease, diabetes, and age-related complications in older patients. Eur Geriatr Med. 2021;12(5):1003-9.

16.          Bartlett DB, Firth CM, Phillips AC, Moss P, Baylis D, Syddall H, et al. The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection. Aging Cell. 2012;11(5):912-5.

17.          Owsley C. Vision and Aging. Annual Review of Vision Science. 2016;2(1):255-71.

18.          Fulop T, Larbi A, Witkowski JM, McElhaney J, Loeb M, Mitnitski A, et al. Aging, frailty and age-related diseases. Biogerontology. 2010;11(5):547-63.

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