Age-Related Diseases

Decline of bodily functions upon aging is a major risk factor for crucial human pathologies. Moreover, because advanced age is the common inherent cause, such chronic disorders frequently take place concurrently as comorbidities in the elderly population.^[1]^[2]^[3]^[4] Among these major pathologies are cancer and cardiovascular disorders. Age-associated diseases impacting the musculoskeletal system are common as well, particularly osteoarthritis, osteoporosis, and sarcopenia. Metabolic disorders such as diabetes and hepatic steatosis are also common with age. Organ and tissue fibrosis, a pathological progression typified by excessive fibrous connective tissue production,^[5] also raises upon aging and is one of the main causes for age-related deterioration of human organs. Overall weakening of the immune system increases susceptibility to infectious diseases.^[6] Neurodegenerative diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, and sensorial malfunctions such as auditory and macular degeneration all increase considerably upon aging.^[7]^[3]^[8]^[9]

Cardiovascular disease is the most frequent cause of death in older adults. This disease class mainly includes coronary artery disease, congestive heart failure, and arrhythmia. Vascular stiffing and remodeling are known to take place throughout normal aging.^[10]^[11]
Atherosclerosis progresses as cholesterol, fat, and other substances in blood form plaques, which cause narrowing of the arteries. This decreases the supply of oxygen-enriched blood to tissues and organs in the body.^[11] Atherosclerosis triggers inflammation and further vascular changes, thus enhancing risk for cardiac and cerebrovascular disorders, peripheral vascular disease, cognitive impairment, and other cardiovascular damage.^[10]^[12]
Cerebrovascular disease (stroke) is another common age-related disease. Stroke happens when blood stops flowing in an area of the brain as a consequence of a disruption of a blood vessel. It is a very critical condition because brain cells deprived of oxygen die quickly, so it can cause death or serious disability.^[13]
Hypertension, the most common chronic disease of older adults, is the major promoter of atherosclerosis.^[14] However, the worth of intensive pharmacotherapy for hypertension in people over age of 75 remains controversial.^[10] Current belief is that aggressive treatment needs to be offered and continued as long as it is well-tolerated.^[14]
Cancer is the second leading cause of death in older adults, most commonly lung, breast, prostate, and colorectal cancers.^[15] Slow-growing tumors are common in this age group. Response to cancer treatment is better related to the physiological status rather than the age.
Osteoarthritis is a very common chronic disorder among older adults and a frequent cause of chronic pain and disability.^[16] The occurrence of osteoarthritis is higher among women than men. Obesity is a risk factor for osteoarthritis, with increasing rate of severe hip and knee arthritis. Osteoarthritis treatments include expensive joint replacement surgery, in addition to intensive rehabilitative treatments. Lower back pain is a common symptom, and its cause is often multifactorial.^[10]
Diabetes rates are on the rise in the aging population. Diabetes is a strong risk factor for cardiovascular disease in older adults.^[17] It is also related to peripheral arterial disease and peripheral neuropathy, causing diabetic foot ulcers and amputations. Osteopenia/Osteoporosis. Osteopenia is normal loss of bone density upon aging. Older adults frequently suffer from osteoporosis, a harsher deterioration of bone density.^[18]
Osteoporosis is associated with an increased rate of bone fractures. Calcium and vitamin D supplementation may be efficient in preventing osteoporosis and bone fractures.
Sarcopenia is an age-related gradual loss of muscle mass and strength, a type of muscle atrophy primarily caused by the natural aging process. It is one of the most important causes of functional decline and loss of independence in older adults. Being physically inactive and eating an unhealthy diet can contribute to the disease.^[19]
Chronic obstructive pulmonary disease (COPD) is a common age-related disease. It is typified by a reduction of airflow into the lungs due to the inflammation of airways, thickening of the lungs lining, and an overproduction of mucus in the air tubes.^[20]
Cognitive decline produces mild short-term memory loss, difficulty finding words, and slower processing, which are all normal features of aging. Deviations from normal brain aging may lead to dementia, manifesting as memory loss, mood changes, confusion, communication difficulties, or deprived judgment.^[21] Rates of dementia rise with age. Alzheimer’s disease is the most common cause of dementia,^[22] but a number of other disorders such as vascular dementia, Lewy body dementia, frontotemporal disorders, Huntington’s disease, and Parkinson’s disease can trigger it as well.

A wide collection of diseases are associated with aging. The figure illustrates the distribution of documents in the CAS Content Collection related to such age-associated pathologies. Among these major diseases are cancer, diabetes, and hypertension. Inflammation, cardiovascular disease, and cognitive disorders are also highly represented

References

↑ López-Otín C et al.: The hallmarks of aging. Cell 2013. (PMID 23746838) [PubMed] [DOI] [Full text] Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.
↑ Seals DR et al.: Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol 2016. (PMID 25639909) [PubMed] [DOI] [Full text] Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio-economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been 'compression of morbidity' and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, 'geroscience', is focused on healthspan extension. Superimposed on this background are new attitudes and demand for 'optimal longevity' - living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio-economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health.
↑ ^3.0 ^3.1 Alle Q et al.: Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues. Int J Mol Sci 2021. (PMID 33924362) [PubMed] [DOI] [Full text] Aging is associated with a progressive and functional decline of all tissues and a striking increase in many "age-related diseases". Although aging has long been considered an inevitable process, strategies to delay and potentially even reverse the aging process have recently been developed. Here, we review emerging rejuvenation strategies that are based on reprogramming toward pluripotency. Some of these approaches may eventually lead to medical applications to improve healthspan and longevity.
↑ Basaraba S.Common Age-Related Diseases and Conditions. https://www.verywellhealth.com/age-related-diseases-2223996#citation-14 (accessed Mar 15, 2023).
↑ Birbrair A et al.: Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner. Stem Cell Res Ther 2014. (PMID 25376879) [PubMed] [DOI] [Full text] INTRODUCTION: Fibrosis, or scar formation, is a pathological condition characterized by excessive production and accumulation of collagen, loss of tissue architecture, and organ failure in response to uncontrolled wound healing. Several cellular populations have been implicated, including bone marrow-derived circulating fibrocytes, endothelial cells, resident fibroblasts, epithelial cells, and recently, perivascular cells called pericytes. We previously demonstrated pericyte functional heterogeneity in skeletal muscle. Whether pericyte subtypes are present in other tissues and whether a specific pericyte subset contributes to organ fibrosis are unknown. METHODS: Here, we report the presence of two pericyte subtypes, type-1 (Nestin-GFP-/NG2-DsRed+) and type-2 (Nestin-GFP+/NG2-DsRed+), surrounding blood vessels in lungs, kidneys, heart, spinal cord, and brain. Using Nestin-GFP/NG2-DsRed transgenic mice, we induced pulmonary, renal, cardiac, spinal cord, and cortical injuries to investigate the contributions of pericyte subtypes to fibrous tissue formation in vivo. RESULTS: A fraction of the lung's collagen-producing cells corresponds to type-1 pericytes and kidney and heart pericytes do not produce collagen in pathological fibrosis. Note that type-1, but not type-2, pericytes increase and accumulate near the fibrotic tissue in all organs analyzed. Surprisingly, after CNS injury, type-1 pericytes differ from scar-forming PDGFRβ + cells. CONCLUSIONS: Pericyte subpopulations respond differentially to tissue injury, and the production of collagen by type-1 pericytes is organ-dependent. Characterization of the mechanisms underlying scar formation generates cellular targets for future anti-fibrotic therapeutics.
↑ Palacio L et al.: Restored immune cell functions upon clearance of senescence in the irradiated splenic environment. Aging Cell 2019. (PMID 31148373) [PubMed] [DOI] [Full text] Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent-associated secretory phenotype (SASP) and expression of p16INK4a in splenic cell populations. We observe splenic T cells exhibit a reduced proliferative response when cultured with allogenic cells in vitro and following viral infection in vivo. Using p16-3MR mice that allow elimination of p16INK4a -positive cells with exposure to ganciclovir, we show that impaired T-cell proliferation is partially reversed, mechanistically dependent on p16INK4a expression and the SASP. Moreover, we found macrophages isolated from irradiated spleens to have a reduced phagocytosis activity in vitro, a defect also restored by the elimination of p16INK4a expression. Our results provide molecular insight on how senescence-inducing IR promotes loss of immune cell fitness, which suggest senolytic drugs may improve immune cell function in aged and patients undergoing cancer treatment.
↑ Hou Y et al.: Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 2019. (PMID 31501588) [PubMed] [DOI] Ageing is the primary risk factor for most neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD). One in ten individuals aged ≥65 years has AD and its prevalence continues to increase with increasing age. Few or no effective treatments are available for ageing-related neurodegenerative diseases, which tend to progress in an irreversible manner and are associated with large socioeconomic and personal costs. This Review discusses the pathogenesis of AD, PD and other neurodegenerative diseases, and describes their associations with the nine biological hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion and altered intercellular communication. The central biological mechanisms of ageing and their potential as targets of novel therapies for neurodegenerative diseases are also discussed, with potential therapies including NAD+ precursors, mitophagy inducers and inhibitors of cellular senescence.
↑ Bowl MR & Dawson SJ: Age-Related Hearing Loss. Cold Spring Harb Perspect Med 2019. (PMID 30291149) [PubMed] [DOI] [Full text] Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive hearing impairment leads to social isolation and is also associated with comorbidities, such as frailty, falls, and late-onset depression. Moreover, there is a growing evidence linking it with cognitive decline and increased risk of dementia. Given the large social and welfare burden that results from ARHL, and because ARHL is potentially a modifiable risk factor for dementia, there is an urgent need for therapeutic interventions to ameliorate age-related auditory decline. However, a prerequisite for design of therapies is knowledge of the underlying molecular mechanisms. Currently, our understanding of ARHL is very limited. Here, we review recent findings from research into ARHL from both human and animal studies and discuss future prospects for advances in our understanding of genetic susceptibility, pathology, and potential therapeutic approaches in ARHL.
↑ Pelletier AL et al.: Vision Loss in Older Adults. Am Fam Physician 2016. (PMID 27479624) [PubMed] Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.
↑ ^10.0 ^10.1 ^10.2 ^10.3 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. (PMID 29312916) [PubMed] [DOI] [Full text] By 2050, the American 85 years old and over population will triple. Clinicians and the public health community need to develop a culture of sensitivity to the needs of this population and its subgroups. Sensory changes, cognitive changes, and weakness may be subtle or may be severe in the heterogeneous population of people over age 85. Falls, cardiovascular disease, and difficulty with activities of daily living are common but not universal. This paper reviews relevant changes of normal aging, diseases, and syndromes common in people over age 85, cognitive and psychological changes, social and environmental changes, and then reviews common discussions which clinicians routinely have with these patients and their families. Some hearing and vision loss are a part of normal aging as is decline in immune function. Cardiovascular disease and osteoporosis and dementia are common chronic conditions at age 85. Osteoarthritis, diabetes, and related mobility disability will increase in prevalence as the population ages and becomes more overweight. These population changes have considerable public health importance. Caregiver support, services in the home, assistive technologies, and promotion of home exercise programs as well as consideration of transportation and housing policies are recommended. For clinicians, judicious prescribing and ordering of tests includes a consideration of life expectancy, lag time to benefit, and patient goals. Furthermore, healthy behaviors starting in early childhood can optimize quality of life among the oldest-old.
↑ ^11.0 ^11.1 Wang JC & Bennett M: Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res 2012. (PMID 22773427) [PubMed] [DOI] Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.
↑ Alexander RW: Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 1995. (PMID 7843763) [PubMed] [DOI] Hypertension is a risk factor for the development of atherosclerosis, although the mechanisms have not been well elucidated. As the cellular and molecular mechanisms of the pathogenesis of atherosclerosis and the effects of hypertension are being more clearly defined, it becomes apparent that the two processes have certain common mechanisms. The endothelium is a likely central focus for the effect of both diseases. There is increasing evidence that atherosclerosis should be viewed fundamentally as an inflammatory disease. Atherogenic stimuli such as hyperlipidemia appear to active the inflammatory response by causing expression of mononuclear leukocyte recruiting mechanisms. The gene for one of these, the vascular cell adhesion molecule-1, is controlled at least in part by transcriptional factors regulated by oxidative stress, which modifies the redox state of the endothelial cell. Alterations in the redox state of the arterial wall also may contribute to vascular smooth muscle cell growth. In a somewhat parallel fashion, there is evidence that hypertension may also exert oxidative stress on the arterial wall. This article reviews evidence that leads to the postulate that hypertension predisposes to and accelerates atherosclerosis at least in part because of synergy between elevated blood pressure and other atherogenic stimuli to induce oxidative stress on the arterial wall.
↑ Stroke. https://medlineplus.gov/stroke.html (accessed Mar 15, 2023).
↑ ^14.0 ^14.1 Wright JT et al.: A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015. (PMID 26551272) [PubMed] [DOI] [Full text] BACKGROUND: The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS: We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS: At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).
↑ Gorina Y et al.: Trends in causes of death among older persons in the United States. Aging Trends 2005. (PMID 19174841) [PubMed]
↑ Older Americans 2016: Key Indicators of Well-Being. The Federal Interagency Forum on Aging-Related Statistics, 2016; https://agingstats.gov/docs/LatestReport/Older-Americans-2016-Key-Indicators-of-WellBeing.pdf. [Google Scholar]
↑ Odden MC et al.: Risk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study. Atherosclerosis 2014. (PMID 25303772) [PubMed] [DOI] [Full text] OBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age. METHODS: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP). RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45). CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.
↑ Padilla Colón CJ et al.: Muscle and Bone Mass Loss in the Elderly Population: Advances in diagnosis and treatment. J Biomed (Syd) 2018. (PMID 30505650) [PubMed] [DOI] [Full text] Aging is the result of different functional changes leading to a substantial reduction of all human capabilities. A variety of anatomical and physiological changes occur with advancing age. These changes are more evident in the elderly population. There are various methods to measure muscle and bone mass loss, but the dual X-ray absorptiometry (DXA) is considered one of the most efficient. The elderly population (65 years and older) has been increasing throughout the years. Loss of muscle mass (sarcopenia) and loss bone mass (osteopenia or osteoporosis) with advancing age, when untreated, represent a major public health problem for the elderly population and may result in loss of independence in later life. Untreated age-related sarcopenia and osteopenia/osteoporosis increase the risk for falls and fractures, making older individuals more susceptible to the development of mobility limitations or severe disabilities that ultimately affect their capacity for independence. In this review, we will discuss the muscle and bone mass loss in the elderly population and advances in diagnosis and treatment.
↑ Walston JD: Sarcopenia in older adults. Curr Opin Rheumatol 2012. (PMID 22955023) [PubMed] [DOI] [Full text] PURPOSE OF REVIEW: Sarcopenia, or the decline of skeletal muscle tissue with age, is one of the most important causes of functional decline and loss of independence in older adults. The purpose of this article is to review the current definitions of sarcopenia, its potential causes and clinical consequences, and the potential for intervention. RECENT FINDINGS: Although no consensus diagnosis has been reached, sarcopenia is increasingly defined by both loss of muscle mass and loss of muscle function or strength. Its cause is widely regarded as multifactorial, with neurological decline, hormonal changes, inflammatory pathway activation, declines in activity, chronic illness, fatty infiltration, and poor nutrition, all shown to be contributing factors. Recent molecular findings related to apoptosis, mitochondrial decline, and the angiotensin system in skeletal muscle have highlighted biological mechanisms that may be contributory. Interventions in general continue to target nutrition and exercise. SUMMARY: Efforts to develop a consensus definition are ongoing and will greatly facilitate the development and testing of novel interventions for sarcopenia. Although pharmaceutical agents targeting multiple biological pathways are being developed, adequate nutrition and targeted exercise remain the gold standard for therapy.
↑ Basics About COPD. https://www.cdc.gov/copd/basics-about.html.
↑ Blazer DG et al.: Cognitive aging: a report from the Institute of Medicine. JAMA 2015. (PMID 25875498) [PubMed] [DOI]
↑ Types of Dementia. https://www.alz.org/alzheimers-dementia/what-is-dementia/types-of-dementia (accessed Mar 15, 2023).
↑ Tenchov R et al.: Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement. ACS Chem Neurosci 2023. (PMID 38095562) [PubMed] [DOI] Aging is a dynamic, time-dependent process that is characterized by a gradual accumulation of cell damage. Continual functional decline in the intrinsic ability of living organisms to accurately regulate homeostasis leads to increased susceptibility and vulnerability to diseases. Many efforts have been put forth to understand and prevent the effects of aging. Thus, the major cellular and molecular hallmarks of aging have been identified, and their relationships to age-related diseases and malfunctions have been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent aging-related research. We review the advances in knowledge and delineate trends in research advancements on aging factors and attributes across time and geography. We also review the current concepts related to the major aging hallmarks on the molecular, cellular, and organismic level, age-associated diseases, with attention to brain aging and brain health, as well as the major biochemical processes associated with aging. Major age-related diseases have been outlined, and their correlations with the major aging features and attributes are explored. We hope this review will be helpful for apprehending the current knowledge in the field of aging mechanisms and progression, in an effort to further solve the remaining challenges and fulfill its potential.

[pmid23746838-1] López-Otín C et al.: The hallmarks of aging. Cell 2013. (PMID 23746838) [PubMed] [DOI] [Full text] Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.

[pmid25639909-2] Seals DR et al.: Physiological geroscience: targeting function to increase healthspan and achieve optimal longevity. J Physiol 2016. (PMID 25639909) [PubMed] [DOI] [Full text] Most nations of the world are undergoing rapid and dramatic population ageing, which presents great socio-economic challenges, as well as opportunities, for individuals, families, governments and societies. The prevailing biomedical strategy for reducing the healthcare impact of population ageing has been 'compression of morbidity' and, more recently, to increase healthspan, both of which seek to extend the healthy period of life and delay the development of chronic diseases and disability until a brief period at the end of life. Indeed, a recently established field within biological ageing research, 'geroscience', is focused on healthspan extension. Superimposed on this background are new attitudes and demand for 'optimal longevity' - living long, but with good health and quality of life. A key obstacle to achieving optimal longevity is the progressive decline in physiological function that occurs with ageing, which causes functional limitations (e.g. reduced mobility) and increases the risk of chronic diseases, disability and mortality. Current efforts to increase healthspan centre on slowing the fundamental biological processes of ageing such as inflammation/oxidative stress, increased senescence, mitochondrial dysfunction, impaired proteostasis and reduced stress resistance. We propose that optimization of physiological function throughout the lifespan should be a major emphasis of any contemporary biomedical policy addressing global ageing. Effective strategies should delay, reduce in magnitude or abolish reductions in function with ageing (primary prevention) and/or improve function or slow further declines in older adults with already impaired function (secondary prevention). Healthy lifestyle practices featuring regular physical activity and ideal energy intake/diet composition represent first-line function-preserving strategies, with pharmacological agents, including existing and new pharmaceuticals and novel 'nutraceutical' compounds, serving as potential complementary approaches. Future research efforts should focus on defining the temporal patterns of functional declines with ageing, identifying the underlying mechanisms and modulatory factors involved, and establishing the most effective lifestyle practices and pharmacological options for maintaining function. Continuing development of effective behavioural approaches for enhancing adherence to healthy ageing practices in diverse populations, and ongoing analysis of the socio-economic costs and benefits of healthspan extension will be important supporting goals. To meet the demands created by rapid population ageing, a new emphasis in physiological geroscience is needed, which will require the collaborative, interdisciplinary efforts of investigators working throughout the translational research continuum from basic science to public health.

[pmid33924362-3] 3.0 ^3.1 Alle Q et al.: Reprogramming: Emerging Strategies to Rejuvenate Aging Cells and Tissues. Int J Mol Sci 2021. (PMID 33924362) [PubMed] [DOI] [Full text] Aging is associated with a progressive and functional decline of all tissues and a striking increase in many "age-related diseases". Although aging has long been considered an inevitable process, strategies to delay and potentially even reverse the aging process have recently been developed. Here, we review emerging rejuvenation strategies that are based on reprogramming toward pluripotency. Some of these approaches may eventually lead to medical applications to improve healthspan and longevity.

[4] Basaraba S.Common Age-Related Diseases and Conditions. https://www.verywellhealth.com/age-related-diseases-2223996#citation-14 (accessed Mar 15, 2023).

[pmid25376879-5] Birbrair A et al.: Type-1 pericytes accumulate after tissue injury and produce collagen in an organ-dependent manner. Stem Cell Res Ther 2014. (PMID 25376879) [PubMed] [DOI] [Full text] INTRODUCTION: Fibrosis, or scar formation, is a pathological condition characterized by excessive production and accumulation of collagen, loss of tissue architecture, and organ failure in response to uncontrolled wound healing. Several cellular populations have been implicated, including bone marrow-derived circulating fibrocytes, endothelial cells, resident fibroblasts, epithelial cells, and recently, perivascular cells called pericytes. We previously demonstrated pericyte functional heterogeneity in skeletal muscle. Whether pericyte subtypes are present in other tissues and whether a specific pericyte subset contributes to organ fibrosis are unknown. METHODS: Here, we report the presence of two pericyte subtypes, type-1 (Nestin-GFP-/NG2-DsRed+) and type-2 (Nestin-GFP+/NG2-DsRed+), surrounding blood vessels in lungs, kidneys, heart, spinal cord, and brain. Using Nestin-GFP/NG2-DsRed transgenic mice, we induced pulmonary, renal, cardiac, spinal cord, and cortical injuries to investigate the contributions of pericyte subtypes to fibrous tissue formation in vivo. RESULTS: A fraction of the lung's collagen-producing cells corresponds to type-1 pericytes and kidney and heart pericytes do not produce collagen in pathological fibrosis. Note that type-1, but not type-2, pericytes increase and accumulate near the fibrotic tissue in all organs analyzed. Surprisingly, after CNS injury, type-1 pericytes differ from scar-forming PDGFRβ + cells. CONCLUSIONS: Pericyte subpopulations respond differentially to tissue injury, and the production of collagen by type-1 pericytes is organ-dependent. Characterization of the mechanisms underlying scar formation generates cellular targets for future anti-fibrotic therapeutics.

[pmid31148373-6] Palacio L et al.: Restored immune cell functions upon clearance of senescence in the irradiated splenic environment. Aging Cell 2019. (PMID 31148373) [PubMed] [DOI] [Full text] Some studies show eliminating senescent cells rejuvenate aged mice and attenuate deleterious effects of chemotherapy. Nevertheless, it remains unclear whether senescence affects immune cell function. We provide evidence that exposure of mice to ionizing radiation (IR) promotes the senescent-associated secretory phenotype (SASP) and expression of p16INK4a in splenic cell populations. We observe splenic T cells exhibit a reduced proliferative response when cultured with allogenic cells in vitro and following viral infection in vivo. Using p16-3MR mice that allow elimination of p16INK4a -positive cells with exposure to ganciclovir, we show that impaired T-cell proliferation is partially reversed, mechanistically dependent on p16INK4a expression and the SASP. Moreover, we found macrophages isolated from irradiated spleens to have a reduced phagocytosis activity in vitro, a defect also restored by the elimination of p16INK4a expression. Our results provide molecular insight on how senescence-inducing IR promotes loss of immune cell fitness, which suggest senolytic drugs may improve immune cell function in aged and patients undergoing cancer treatment.

[pmid31501588-7] Hou Y et al.: Ageing as a risk factor for neurodegenerative disease. Nat Rev Neurol 2019. (PMID 31501588) [PubMed] [DOI] Ageing is the primary risk factor for most neurodegenerative diseases, including Alzheimer disease (AD) and Parkinson disease (PD). One in ten individuals aged ≥65 years has AD and its prevalence continues to increase with increasing age. Few or no effective treatments are available for ageing-related neurodegenerative diseases, which tend to progress in an irreversible manner and are associated with large socioeconomic and personal costs. This Review discusses the pathogenesis of AD, PD and other neurodegenerative diseases, and describes their associations with the nine biological hallmarks of ageing: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, mitochondrial dysfunction, cellular senescence, deregulated nutrient sensing, stem cell exhaustion and altered intercellular communication. The central biological mechanisms of ageing and their potential as targets of novel therapies for neurodegenerative diseases are also discussed, with potential therapies including NAD+ precursors, mitophagy inducers and inhibitors of cellular senescence.

[pmid30291149-8] Bowl MR & Dawson SJ: Age-Related Hearing Loss. Cold Spring Harb Perspect Med 2019. (PMID 30291149) [PubMed] [DOI] [Full text] Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly. This progressive hearing impairment leads to social isolation and is also associated with comorbidities, such as frailty, falls, and late-onset depression. Moreover, there is a growing evidence linking it with cognitive decline and increased risk of dementia. Given the large social and welfare burden that results from ARHL, and because ARHL is potentially a modifiable risk factor for dementia, there is an urgent need for therapeutic interventions to ameliorate age-related auditory decline. However, a prerequisite for design of therapies is knowledge of the underlying molecular mechanisms. Currently, our understanding of ARHL is very limited. Here, we review recent findings from research into ARHL from both human and animal studies and discuss future prospects for advances in our understanding of genetic susceptibility, pathology, and potential therapeutic approaches in ARHL.

[pmid27479624-9] Pelletier AL et al.: Vision Loss in Older Adults. Am Fam Physician 2016. (PMID 27479624) [PubMed] Vision loss affects 37 million Americans older than 50 years and one in four who are older than 80 years. The U.S. Preventive Services Task Force concludes that current evidence is insufficient to assess the balance of benefits and harms of screening for impaired visual acuity in adults older than 65 years. However, family physicians play a critical role in identifying persons who are at risk of vision loss, counseling patients, and referring patients for disease-specific treatment. The conditions that cause most cases of vision loss in older patients are age-related macular degeneration, glaucoma, ocular complications of diabetes mellitus, and age-related cataracts. Vitamin supplements can delay the progression of age-related macular degeneration. Intravitreal injection of a vascular endothelial growth factor inhibitor can preserve vision in the neovascular form of macular degeneration. Medicated eye drops reduce intraocular pressure and can delay the progression of vision loss in patients with glaucoma, but adherence to treatment is poor. Laser trabeculoplasty also lowers intraocular pressure and preserves vision in patients with primary open-angle glaucoma, but long-term studies are needed to identify who is most likely to benefit from surgery. Tight glycemic control in adults with diabetes slows the progression of diabetic retinopathy, but must be balanced against the risks of hypoglycemia and death in older adults. Fenofibrate also slows progression of diabetic retinopathy. Panretinal photocoagulation is the mainstay of treatment for diabetic retinopathy, whereas vascular endothelial growth factor inhibitors slow vision loss resulting from diabetic macular edema. Preoperative testing before cataract surgery does not improve outcomes and is not recommended.

[pmid29312916-10] 10.0 ^10.1 ^10.2 ^10.3 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. (PMID 29312916) [PubMed] [DOI] [Full text] By 2050, the American 85 years old and over population will triple. Clinicians and the public health community need to develop a culture of sensitivity to the needs of this population and its subgroups. Sensory changes, cognitive changes, and weakness may be subtle or may be severe in the heterogeneous population of people over age 85. Falls, cardiovascular disease, and difficulty with activities of daily living are common but not universal. This paper reviews relevant changes of normal aging, diseases, and syndromes common in people over age 85, cognitive and psychological changes, social and environmental changes, and then reviews common discussions which clinicians routinely have with these patients and their families. Some hearing and vision loss are a part of normal aging as is decline in immune function. Cardiovascular disease and osteoporosis and dementia are common chronic conditions at age 85. Osteoarthritis, diabetes, and related mobility disability will increase in prevalence as the population ages and becomes more overweight. These population changes have considerable public health importance. Caregiver support, services in the home, assistive technologies, and promotion of home exercise programs as well as consideration of transportation and housing policies are recommended. For clinicians, judicious prescribing and ordering of tests includes a consideration of life expectancy, lag time to benefit, and patient goals. Furthermore, healthy behaviors starting in early childhood can optimize quality of life among the oldest-old.

[pmid22773427-11] 11.0 ^11.1 Wang JC & Bennett M: Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res 2012. (PMID 22773427) [PubMed] [DOI] Atherosclerosis is classed as a disease of aging, such that increasing age is an independent risk factor for the development of atherosclerosis. Atherosclerosis is also associated with premature biological aging, as atherosclerotic plaques show evidence of cellular senescence characterized by reduced cell proliferation, irreversible growth arrest and apoptosis, elevated DNA damage, epigenetic modifications, and telomere shortening and dysfunction. Not only is cellular senescence associated with atherosclerosis, there is growing evidence that cellular senescence promotes atherosclerosis. This review examines the pathology of normal vascular aging, the evidence for cellular senescence in atherosclerosis, the mechanisms underlying cellular senescence including reactive oxygen species, replication exhaustion and DNA damage, the functional consequences of vascular cell senescence, and the possibility that preventing accelerated cellular senescence is a therapeutic target in atherosclerosis.

[pmid7843763-12] Alexander RW: Theodore Cooper Memorial Lecture. Hypertension and the pathogenesis of atherosclerosis. Oxidative stress and the mediation of arterial inflammatory response: a new perspective. Hypertension 1995. (PMID 7843763) [PubMed] [DOI] Hypertension is a risk factor for the development of atherosclerosis, although the mechanisms have not been well elucidated. As the cellular and molecular mechanisms of the pathogenesis of atherosclerosis and the effects of hypertension are being more clearly defined, it becomes apparent that the two processes have certain common mechanisms. The endothelium is a likely central focus for the effect of both diseases. There is increasing evidence that atherosclerosis should be viewed fundamentally as an inflammatory disease. Atherogenic stimuli such as hyperlipidemia appear to active the inflammatory response by causing expression of mononuclear leukocyte recruiting mechanisms. The gene for one of these, the vascular cell adhesion molecule-1, is controlled at least in part by transcriptional factors regulated by oxidative stress, which modifies the redox state of the endothelial cell. Alterations in the redox state of the arterial wall also may contribute to vascular smooth muscle cell growth. In a somewhat parallel fashion, there is evidence that hypertension may also exert oxidative stress on the arterial wall. This article reviews evidence that leads to the postulate that hypertension predisposes to and accelerates atherosclerosis at least in part because of synergy between elevated blood pressure and other atherogenic stimuli to induce oxidative stress on the arterial wall.

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[pmid26551272-14] 14.0 ^14.1 Wright JT et al.: A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med 2015. (PMID 26551272) [PubMed] [DOI] [Full text] BACKGROUND: The most appropriate targets for systolic blood pressure to reduce cardiovascular morbidity and mortality among persons without diabetes remain uncertain. METHODS: We randomly assigned 9361 persons with a systolic blood pressure of 130 mm Hg or higher and an increased cardiovascular risk, but without diabetes, to a systolic blood-pressure target of less than 120 mm Hg (intensive treatment) or a target of less than 140 mm Hg (standard treatment). The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. RESULTS: At 1 year, the mean systolic blood pressure was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group. The intervention was stopped early after a median follow-up of 3.26 years owing to a significantly lower rate of the primary composite outcome in the intensive-treatment group than in the standard-treatment group (1.65% per year vs. 2.19% per year; hazard ratio with intensive treatment, 0.75; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). All-cause mortality was also significantly lower in the intensive-treatment group (hazard ratio, 0.73; 95% CI, 0.60 to 0.90; P=0.003). Rates of serious adverse events of hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure, but not of injurious falls, were higher in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS: Among patients at high risk for cardiovascular events but without diabetes, targeting a systolic blood pressure of less than 120 mm Hg, as compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal major cardiovascular events and death from any cause, although significantly higher rates of some adverse events were observed in the intensive-treatment group. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01206062.).

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[pmid25303772-17] Odden MC et al.: Risk factors for cardiovascular disease across the spectrum of older age: the Cardiovascular Health Study. Atherosclerosis 2014. (PMID 25303772) [PubMed] [DOI] [Full text] OBJECTIVE: The associations of some risk factors with cardiovascular disease (CVD) are attenuated in older age; whereas others appear robust. The present study aimed to compare CVD risk factors across older age. METHODS: Participants (n = 4883) in the Cardiovascular Health Study free of prevalent CVD, were stratified into three age groups: 65-74, 75-84, 85+ years. Traditional risk factors included systolic blood pressure (BP), LDL-cholesterol, HDL-cholesterol, obesity, and diabetes. Novel risk factors included kidney function, C-reactive protein (CRP), and N-terminal pro-B-type natriuretic peptide (NT pro-BNP). RESULTS: There were 1498 composite CVD events (stroke, myocardial infarction, and cardiovascular death) over 5 years. The associations of high systolic BP and diabetes appeared strongest, though both were attenuated with age (p-values for interaction = 0.01 and 0.002, respectively). The demographic-adjusted hazard ratios (HR) for elevated systolic BP were 1.79 (95% confidence interval: 1.49, 2.15), 1.59 (1.37, 1.85) and 1.10 (0.86, 1.41) in participants aged 65-74, 75-84, 85+, and for diabetes, 2.36 (1.89, 2.95), 1.55 (1.27, 1.89), 1.51 (1.10, 2.09). The novel risk factors had consistent associations with the outcome across the age spectrum; low kidney function: 1.69 (1.31, 2.19), 1.61 (1.36, 1.90), and 1.57 (1.16, 2.14) for 65-74, 75-84, and 85+ years, respectively; elevated CRP: 1.54 (1.28, 1.87), 1.33 (1.13, 1.55), and 1.51 (1.15, 1.97); elevated NT pro-BNP: 2.67 (1.96, 3.64), 2.71 (2.25, 3.27), and 2.18 (1.43, 3.45). CONCLUSIONS: The associations of most traditional risk factors with CVD were minimal in the oldest old, whereas diabetes, eGFR, CRP, and NT pro-BNP were associated with CVD across older age.

[pmid30505650-18] Padilla Colón CJ et al.: Muscle and Bone Mass Loss in the Elderly Population: Advances in diagnosis and treatment. J Biomed (Syd) 2018. (PMID 30505650) [PubMed] [DOI] [Full text] Aging is the result of different functional changes leading to a substantial reduction of all human capabilities. A variety of anatomical and physiological changes occur with advancing age. These changes are more evident in the elderly population. There are various methods to measure muscle and bone mass loss, but the dual X-ray absorptiometry (DXA) is considered one of the most efficient. The elderly population (65 years and older) has been increasing throughout the years. Loss of muscle mass (sarcopenia) and loss bone mass (osteopenia or osteoporosis) with advancing age, when untreated, represent a major public health problem for the elderly population and may result in loss of independence in later life. Untreated age-related sarcopenia and osteopenia/osteoporosis increase the risk for falls and fractures, making older individuals more susceptible to the development of mobility limitations or severe disabilities that ultimately affect their capacity for independence. In this review, we will discuss the muscle and bone mass loss in the elderly population and advances in diagnosis and treatment.

[pmid22955023-19] Walston JD: Sarcopenia in older adults. Curr Opin Rheumatol 2012. (PMID 22955023) [PubMed] [DOI] [Full text] PURPOSE OF REVIEW: Sarcopenia, or the decline of skeletal muscle tissue with age, is one of the most important causes of functional decline and loss of independence in older adults. The purpose of this article is to review the current definitions of sarcopenia, its potential causes and clinical consequences, and the potential for intervention. RECENT FINDINGS: Although no consensus diagnosis has been reached, sarcopenia is increasingly defined by both loss of muscle mass and loss of muscle function or strength. Its cause is widely regarded as multifactorial, with neurological decline, hormonal changes, inflammatory pathway activation, declines in activity, chronic illness, fatty infiltration, and poor nutrition, all shown to be contributing factors. Recent molecular findings related to apoptosis, mitochondrial decline, and the angiotensin system in skeletal muscle have highlighted biological mechanisms that may be contributory. Interventions in general continue to target nutrition and exercise. SUMMARY: Efforts to develop a consensus definition are ongoing and will greatly facilitate the development and testing of novel interventions for sarcopenia. Although pharmaceutical agents targeting multiple biological pathways are being developed, adequate nutrition and targeted exercise remain the gold standard for therapy.

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[pmid38095562-23] Tenchov R et al.: Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement. ACS Chem Neurosci 2023. (PMID 38095562) [PubMed] [DOI] Aging is a dynamic, time-dependent process that is characterized by a gradual accumulation of cell damage. Continual functional decline in the intrinsic ability of living organisms to accurately regulate homeostasis leads to increased susceptibility and vulnerability to diseases. Many efforts have been put forth to understand and prevent the effects of aging. Thus, the major cellular and molecular hallmarks of aging have been identified, and their relationships to age-related diseases and malfunctions have been explored. Here, we use data from the CAS Content Collection to analyze the publication landscape of recent aging-related research. We review the advances in knowledge and delineate trends in research advancements on aging factors and attributes across time and geography. We also review the current concepts related to the major aging hallmarks on the molecular, cellular, and organismic level, age-associated diseases, with attention to brain aging and brain health, as well as the major biochemical processes associated with aging. Major age-related diseases have been outlined, and their correlations with the major aging features and attributes are explored. We hope this review will be helpful for apprehending the current knowledge in the field of aging mechanisms and progression, in an effort to further solve the remaining challenges and fulfill its potential.

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Age-Related Diseases

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References