老化の定義は以下のようなものがある。生理学的な定義であるが興味ある人は読んでみてほしい
機械翻訳を最初に記載します。
********************
紹介
老化は私たちの人生を通して私たち全員が経験するほとんど普遍的な真理ですが、臨床医がこのプロセスの臨床的および疫学的関連性の両方を理解することが重要です。老化は、特別なケアと管理を必要とする身体のシステムのスペクトル全体にわたって様々な変化をもたらします。2050年までに65歳以上の成人数は8,850万人を超えると推定されており、医療従事者や病院システムに対する需要が高まるに値すると推定されています。技術は現代医学の能力を大幅に拡大することを可能にしているが、多くの副作用が時間の経過とともに現れ、そのすべてが医学全体と同じ速度で発達しているわけではない。これは、新しいスクリーニング方法を開発し、特定の生物医学技術の出現前に非常に迅速に致命的であることが判明した可能性のある疾患の長引く管理に対処し、人生の後半に慢性疾患や病気の落とし穴を避けるために幼い頃に健康とウェルネスのライフスタイル対策を促進し、開発することを意味します。[2]
懸念事項
生物学的に言えば、老化、または老化は、生物学的観点から起こるプロセスをより正確に描写するものであり、生物の中で時間の経過とともに起こる特定の再生および生物保護メカニズムの喪失の慢性的で正常な集大成である。この考え方を人間に広げれば、デフォルトで老化がプロ疾患状態を必要としていることを明確に確認し始める。この記事では、通常の老化プロセスの結果として生じる最も懸念される問題のいくつかを特徴付けようとします。
-
臓器系 - 老化に伴う一般的な医学的および外科的問題
-
神経学的 - 脳血管障害、アルツハイマー病、およびその他の認知症、パーキンソン病
-
心血管 - 冠動脈疾患およびアテローム性動脈硬化症、心不全、高血圧、血液性悪性腫瘍
-
肺 - 慢性閉塞性肺疾患、肺癌、肺炎
-
筋骨格系 - 骨粗鬆症、変形性関節症、骨折、骨格悪性腫瘍
-
内分泌 - 糖尿病性
-
泌尿器科/婦人科 - 尿路感染症、泌尿生殖器癌、子宮頸癌、乳癌、前立腺癌
-
特殊感覚 - プレスビクシス、プレスビオペ、白内障、黄斑変性症、緑内障
-
胃腸 - 吸収不良、GI悪性腫瘍、腸閉塞、憩室疾患
-
その他の特別な考慮事項 - 独立、転倒、高齢者虐待と無視、精神医学的懸念、皮膚の崩壊、皮膚の涙
携帯
細胞レベルでは、細胞増殖が最終的に全停止の時点まで遅くなるにつれて、一次老化関連のメカニズムが発生する。さらに、いくつかの文献は、タンパク質産生の増加、アポトーシス耐性、および細胞生化学的活性における変化が、上記のように、この状態で多くの同様の細胞の蓄積と組み合わされ、老化と関連する表現型にも寄与することを示唆している。若年期と中年期を通じて老化するにつれて、私たちの体内のこれらの老化細胞の全体的な量は比較的低く、身体のまだ高い数の細胞によって克服するために管理可能なままであり、まだ老化し、正常な生理学に沿って機能していません。それは、私たちの体内の老化細胞の数とその後の蓄積に対する能力の閾値を超えるポイントであり、その後の組織の蓄積は、老化に関連する病気を見始めます。例えば、変形性関節症の発症は、患部内の老化細胞の蓄積に関連しており、その後の変性につながり、最終的にその関節の機能と移動性の有用性が低下していると考える人もいます。[4]
発達
私たちが人生に入った瞬間から、私たちの老化プロセスが始まります。それは遅い、慢性的なプロセスであり、その起源は必ずしもよく理解されているわけではないが、普遍的に受け入れられている。私たちの老化プロセスの起源の物語に関するいくつかの理論が浮上しています。老化は、非常に高度な年齢がほとんど進化的利益を持たないために起こる生物学的に「プログラムされた」メカニズムの一種であり、生物が何らかの長期間老化することができれば、若い世代の生物が主に老化した生物よりも生殖能力が高いと考えている希少資源のもう一つの競争相手になるだろうという考え方を持つ人もいます。[5]具体的には、人間にプログラム老化のこの考え方を外挿することによって, 我々の老化は、遺伝的に事前にプログラムされたホルモンの調停に起因する我々の老化が発生することを、時間をかけて提案されています.すなわち、成長ホルモンとインスリン経路は、発達に関連するとよく理解されており、神経内分泌系によって制御され、様々な形態の遺伝子発現とその後のホルモン変動を介して生物の老化プロセスの仲介において中心的な役割を果たすことができる。
老化の発展を支えるもう一つの理論は、私たちの寿命を通して細胞レベルでの損傷の蓄積です。具体的には、この点に関しては、活性酸素種の生成とDNAのメチル化変化が、老化に進む根本的なメカニズムである可能性が示唆されています。この老化の潜在的なメカニズムは、活性酸素種の発達にも密接に結びついており、酸化的損傷を引き起こし得る[
関係する臓器系
事実上すべての器官系は、老化に関連する特定の生理学的変化に関与している。累積的に、細胞のターンオーバーの喪失、粘膜の機能低下、悪液質および骨格筋量の無駄、血管コンプライアンスの増加アテローム硬化性低下、および脳萎縮はすべて、老化に見られる様々な変化に寄与する。老化の正常な過程と、疾患の設定で起こる病理変化を区別することは不可欠であるが、補償機構の減少または全損失のために著しく抜本的である。
Specifically, some of the many changes which occur are listed by organ system below.
Neurological
Abnormal compensatory mechanisms predispose individuals to neurodegeneration and dementia, Parkinson disease, and overall cerebral atrophy are observable in aging individuals.[7]
Gastrointestinal
Changes in taste and smell, altered gut motility, and intestinal microbiota abnormalities can lead to age-related anorexia and subsequent caloric and/or nutritional deficiency. The weakening of smooth muscle in the intestinal tract can promote the development of diverticular disease and can play a role in bowel obstructions or constipation. Decreased metabolic activity, specifically in the liver, can lead to alterations in drug metabolism.[8]
Renal
Aging leads to a reduced number of functional glomeruli and an increased prevalence of sclerotic changes within the glomeruli or renal vasculature. Additionally, there is a normal decrease in GFR observed in advanced age, but this places the elderly at much higher risk for complications in the event that they develop chronic or acute kidney disease, as they have less functional glomeruli as a result of normal aging physiology.[9]
Cardiovascular
Aging lowers the threshold for cardiovascular disease development. This is mostly due to a loss of cardioprotective and compensatory mechanisms that otherwise help to prevent the development of serious cardiac disease. For example, vascular stiffening, increased left ventricular wall thickness, myocardial fibrosis, calcification of valves and their related structures, as well as decreased aerobic tolerance and increase of problematic cardiomyocyte remodeling all potentially increase risks for cardiovascular diseases with aging.[10]
Respiratory
Age-related changes in the respiratory system primarily center upon the loss of elasticity and decrease in chest wall compliance leading to increased work of breathing, as well as increased residual volume and functional residual capacity. Additionally, decreased strength and function of respiratory muscles is observable. All of these changes drop an aging patient’s threshold in compensating for an acute illness or respiratory failure.[11]
Endocrine
Age-related decline in endocrine function can yield various effects within the realm of metabolic and hormonal control in aging populations. Thyroxin and triiodothyronine secretion decrease, resulting in overall decreased metabolic activity, circadian rhythms become altered, and patients are prone to reduced REM sleep. Alterations in glucose metabolism and, specifically, insulin secretion develop with age, promoting the development of diabetes mellitus in the elderly. Specific sex-linked endocrine function is impaired or altered with age as well. Women typically experience menopause in their sixth decade of life, which is accompanied by an increased risk of cardiovascular disease, loss of bone mass, and atrophy of estrogen-responsive tissue.[12]
Function
The process of aging is well understood to be part of the natural progression of the human life cycle. Simply by virtue of cellular degradation combined with the loss of biosynthetic and cellular repair mechanisms that might have compensated for this degradation in our youth, aging is a chronic and unavoidable state that we will eventually all enter.
Mechanism
On a cellular level, aging is believed to result from a variety of factors related to cellular senescence. The overarching notion is that human cells can only replicate a finite number of times before they become senescent. Previous research in this field has shown that as a cell divides, telomeres on the DNA strand become gradually shortened.[13] The mechanism by which this occurs can be summarized by understanding that the telomeres appear to serve a chromosome-protective role. As the telomere length decreases, so too are the protective qualities of the proteins, which normally at the distal ends of the telomere and allow DNA repair enzymes to recognize telomeres amongst sites of DNA damage. As a result, the loss of telomere length and concomitant loss of these protective proteins exposes the ends of the chromosomes to damage by DNA repair enzymes.[14] This process is compounded by DNA repair complex-mediated activation of transcription factor p53, which, in conjunction with cyclin-dependent kinase inhibitor p21, can result in subsequent senescence of cells and, ultimately, cessation of their metabolic and replicative functions.[15]
Related Testing
Tests relevant to aging and its associated physiology are system and patient or pathology-specific. For example, in an elderly patient with confusion or alterations in neurological status, it might be valuable to administer the mini-mental state examination (MMSE) or, whereas in a patient of 20 years old with similar symptoms, the underlying pathology is likely, not due to dementia as it would be in the elderly patient, so different testing would be necessary.[16] Additionally, in patients with advanced age, certain routine screening tools or tests require implementation due to the unique set of health concerns experienced at older ages. For example, men should receive digital rectal exams for prostate cancer screening; women mammography for breast cancer screening, and annual colonoscopies are a great screening tool to exclude colon cancer in men and women alike. The purpose of such screening tools is to discover disease as early as possible in its clinical course and identify unhealthy lifestyles and behaviors for which the patient can then receive counseling.[17] Such tools are especially valuable in such an aging population as it is well understood that disease risk increases with age.
Pathophysiology
Three distinct processes can reasonably explain the pathophysiology underlying the aging process:
Production of Free Radicals
Free radicals are well known in the biochemical world as a normal byproduct of healthy physiology in well-regulated, relatively small amounts. They exist as a molecule with a single, unpaired valence electron, rendering them highly reactive in the presence of other substances as they attempt to interact with other substances in an effort to obtain additional valence electrons and balance the electron configuration.[18] The exact underlying mechanisms underlying the downstream adverse effects of free radical generation and subsequent interaction with cellular components is beyond the scope of this paper, but it bears mentioning that free radicals can denature proteins, destroy membrane lipids, nucleic acids, and certain organelles such as lysosomes and proteasomes.[19] The importance of understanding free radical or reactive oxygen species-derived degenerative changes is that the belief is that accumulated cellular damage via these molecules will—in time—cumulatively overwhelm the cell’s damage repair mechanisms, leading to the eventual physiologic collapse of first, the cell, then the whole organism.[18]
Glycation
Advanced glycosylation end-products form when reactions occur between aldehyde groups of reducing sugars and amino groups of proteins. The formation of these metabolic products occurs in a fashion dependent on elevated blood glucose.[20] In aging individuals, glycemic control becomes less regulated, and glucose tolerance can undergo significant alteration. The predominance of advanced glycosylation end-products can result in such abnormalities as vascular fibrosis, thickened basement membranes, impaired lipid metabolism, and reduced collagenous elasticity. Furthermore, advanced glycosylation end-products are associated with the induction of inflammatory responses, resulting in the release of inflammatory substances and reactive oxygen species, causing further tissue damage.[18]
Reduced Regenerative Capacity
In healthy individuals, a balance exists between one cell’s apoptosis and the maturation and healthy development of another cell that essentially takes the place of the first. Researchers believe that mechanisms within the cell cycle control both the programmed death of a senescent cell but also signal externally to other cells the need for the development of a new, healthy cell to backfill whatever metabolic demands the senescent cell might have been meeting. The progression between stages in the cell cycle is controlled by regulatory proteins, whose function demonstrably declines in senescent cells compared to younger, healthy cells. The ability of these protein-derived signaling pathways to communicate the need for cell regeneration and maturation in the healthy, young cells seems to be reduced in the aging process, while the pro-apoptotic pathway signaling mechanisms continue to function, leading to a net decline in functional, healthy cells.[18]
Clinical Significance
The aging process is a natural phenomenon that occurs due to a variety of loosely understood mechanisms. Via a combination of telomeric shortening, which triggers pro-apoptotic pathways when sensed in the cell cycle, which subsequently triggers inflammatory mediators and the release of damaging reactive oxygen species, our bodies and their ability to maintain physiologic homeostasis degrade with time. Moreover, so too does the body's ability to regenerate or reproduce healthy cells and tissues as we age. The aging process brings with it phenotypical changes that clinicians must understand and consider when caring for aging patients.
It is essential to recognize that aging involves a great deal of interplay between lifestyle and genetics. An individual who maintains a healthy lifestyle, has access to adequate, routine medical care and screenings, and enters into late adulthood with a clean bill of health will experience a vastly different aging process than someone who is sedentary, makes poor diet and lifestyle choices, and has lived with chronic disease before and upon entry into late adulthood.
Aging is relevant to clinical care and management because it often implies underlying derangements of normal physiology. As an example, this article mentioned earlier that urinary tract infections are more common in the elderly. Some patients may experience an increased frequency of falls due to the weakness imposed by their urinary tract infection or their bladder urgency forcing them to attempt to hurriedly make it to a toilet. Clinicians must remain vigilant of the manifestations of disease in aging, and likewise, the presentation of physiologic derangements that pose a potential risk to health, like falls and urinary tract infections.[21] Aging, although a normal aspect of typical physiology, does incur some manifestations of physiologic derangement that clinicians should learn to interpret in context.
Review Questions
References
- 1.
-
Pallin DJ, Espinola JA, Camargo CA. US population aging and demand for inpatient services. J Hosp Med. 2014 Mar;9(3):193-6. [PubMed]
- 2.
-
Partridge L, Deelen J, Slagboom PE. Facing up to the global challenges of ageing. Nature. 2018 Sep;561(7721):45-56. [PubMed]
- 3.
-
Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of Cellular Senescence. Trends Cell Biol. 2018 Jun;28(6):436-453. [PubMed]
- 4.
-
Tchkonia T, Kirkland JL. Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies. JAMA. 2018 Oct 02;320(13):1319-1320. [PubMed]
- 5.
-
Goldsmith TC. On the programmed/non-programmed aging controversy. Biochemistry (Mosc). 2012 Jul;77(7):729-32. [PubMed]
- 6.
-
コスマンD、ウィグナルJ、ルイスA、アルパートA、セレッティDP、パークL、ダウアーSK、ギリスS、ウルダルDL。マウス細胞におけるヒトインターロイキン-2受容体の高レベル安定発現は、低親和性インターロイキン-2結合部位のみを生成する。モル免疫.1986年9月23(9):935-41。 [パブメド]
- 7.
- 8.
- 9.
- 10.
- 11.
- 12.
- 13.
- 14.
- 15.
- 16.
- 17.
- 18.
- 19.
- 20.
- 21.
***********************
Physiology, Aging - StatPearls - NCBI Bookshelf (nih.gov)
Introduction
Although aging is an almost universal truth that we all experience throughout our lives, it is vital that clinicians understand both the clinical and epidemiological relevance of this process. Senescence brings a variety of changes across the spectrum of the body’s systems, which require special care and management. Estimates are that the number of adults older than 65 will reach upwards of 88.5 million by 2050, which will surely place a higher demand for healthcare providers and hospital systems.[1] While technology has allowed for a massive expansion of the capabilities of modern medical science, many side effects have appeared over time, of which not all have developed at the same rate as medical science in general—not the least of which is our overall prolonged life expectancies. This implies a particular impetus to develop new screening methods, cope with protracted management of disease which might have proved fatal quite quickly before the advent of certain biomedical technologies, and to promote and develop health and wellness lifestyle measures at an early age to avoid the pitfalls of chronic illness and disease later in life.[2]
Issues of Concern
Biologically speaking, aging—or senescence, which more accurately depicts the processes occurring from a biological standpoint—is a chronic, normal culmination of the loss of specific regenerative and bioprotective mechanisms that occur over time in an organism.[3] Expanding this idea to the human being, we can clearly begin to ascertain that aging by default necessitates a pro-disease state. This article will attempt to characterize some of the most concerning issues that arise as a result of the normal aging process, without, of course, being an entirely exhaustive list of all possible manifestations.
-
Organ System - Common medical and surgical Issues associated with aging
-
Neurological - Cerebrovascular accident, Alzheimer disease, and other dementias, Parkinson disease
-
Cardiovascular - Coronary artery disease and atherosclerosis, heart failure, hypertension, hematologic malignancy
-
Pulmonary - Chronic obstructive pulmonary disease, lung cancer, pneumonia
-
Musculoskeletal - Osteoporosis, osteoarthritis, fractures, skeletal malignancies
-
Endocrine - Diabetes mellitus
-
Urological/Gynecologic - Urinary tract infections, urogenital cancer, cervical cancers, breast cancers, prostate cancer
-
Special Senses - Presbycusis, presbyopia, cataract, macular degeneration, glaucoma
-
Gastrointestinal - Malabsorption, GI malignancies, bowel obstruction, diverticular disease
-
Other special consideration - Independence, falls, elder abuse and neglect, psychiatric concerns, skin breakdown, skin tears
Cellular
At the cellular level, the primary aging-related mechanisms occur as cell proliferation slows eventually to the point of total cessation. Additionally, some literature suggests that increased protein production, apoptotic resistance, and alterations in cellular biochemical activity combined with an accumulation of many like cells in this state, as mentioned above, also contribute to the phenotype we associate with aging. As we age through young and middle adulthood, the overall amount of these senescent cells within our bodies remains relatively low and manageable to overcome by the body’s still higher number of cells, which are not yet senescent and functioning in line with normal physiology. It is the point at which we cross the threshold of capacity relative to the number of senescent cells within our body and then their subsequent accumulation in our tissues that we begin to see disease associated with aging. For instance, some hold that the development of osteoarthritis is associated with accumulations of senescent cells within the affected joint regions, leading to subsequent degeneration and eventually decreased function of that joint and its usefulness in our mobility.[4]
Development
From the moment we enter life, our aging process begins. It is a slow, chronic process, the origins of which are not necessarily well understood but universally accepted. Several theories have emerged as to the origin story of our aging processes. Some hold that aging is a sort of biologically “programmed” mechanism that occurs because extremely advanced age holds little evolutionary benefit, the idea being that if organisms could age for some prolonged-time period, they would be yet another competitor for scarce resources that are also being pursued by a younger generation of organisms mostly thought of as being more capable of reproduction than their aged counterparts.[5] By extrapolating this idea of programmed senescence to human beings specifically, it has been proposed time over that our aging occurs resulting from genetically pre-programmed hormonal mediation. That is, growth hormone and the insulin pathway, which are well-understood to be associated with development, are controlled by the neuroendocrine system and can play a central role in the mediation of an organism’s aging process via various forms of gene expression and subsequent hormonal fluctuance.
Yet another theory that underpins the development of aging is that of accumulations of damage at the cellular level throughout our lifespan. More specifically, to this point, the suggestion is that the generation of reactive oxygen species and the resulting methylation changes in our DNA could be the underlying mechanism by which we progress into aging.[6] This potential mechanism of aging is also closely tied to the development of reactive oxygen species, which results in oxidative damage.
Organ Systems Involved
Virtually all organ systems are involved in the particular physiologic changes associated with aging. Cumulatively, the loss of cell turnover, decreased function of mucous membranes, cachexia and skeletal muscle mass wasting, increased atherosclerotic decrease in vascular compliance, and cerebral atrophy eventually all contribute to the variety of changes we see in aging. It is essential to distinguish the normal processes of aging from those pathologic changes that occur in the setting of disease but are markedly more drastic due to the decreased or total loss of compensatory mechanisms.
Specifically, some of the many changes which occur are listed by organ system below.
Neurological
Abnormal compensatory mechanisms predispose individuals to neurodegeneration and dementia, Parkinson disease, and overall cerebral atrophy are observable in aging individuals.[7]
Gastrointestinal
Changes in taste and smell, altered gut motility, and intestinal microbiota abnormalities can lead to age-related anorexia and subsequent caloric and/or nutritional deficiency. The weakening of smooth muscle in the intestinal tract can promote the development of diverticular disease and can play a role in bowel obstructions or constipation. Decreased metabolic activity, specifically in the liver, can lead to alterations in drug metabolism.[8]
Renal
Aging leads to a reduced number of functional glomeruli and an increased prevalence of sclerotic changes within the glomeruli or renal vasculature. Additionally, there is a normal decrease in GFR observed in advanced age, but this places the elderly at much higher risk for complications in the event that they develop chronic or acute kidney disease, as they have less functional glomeruli as a result of normal aging physiology.[9]
Cardiovascular
Aging lowers the threshold for cardiovascular disease development. This is mostly due to a loss of cardioprotective and compensatory mechanisms that otherwise help to prevent the development of serious cardiac disease. For example, vascular stiffening, increased left ventricular wall thickness, myocardial fibrosis, calcification of valves and their related structures, as well as decreased aerobic tolerance and increase of problematic cardiomyocyte remodeling all potentially increase risks for cardiovascular diseases with aging.[10]
Respiratory
Age-related changes in the respiratory system primarily center upon the loss of elasticity and decrease in chest wall compliance leading to increased work of breathing, as well as increased residual volume and functional residual capacity. Additionally, decreased strength and function of respiratory muscles is observable. All of these changes drop an aging patient’s threshold in compensating for an acute illness or respiratory failure.[11]
Endocrine
Age-related decline in endocrine function can yield various effects within the realm of metabolic and hormonal control in aging populations. Thyroxin and triiodothyronine secretion decrease, resulting in overall decreased metabolic activity, circadian rhythms become altered, and patients are prone to reduced REM sleep. Alterations in glucose metabolism and, specifically, insulin secretion develop with age, promoting the development of diabetes mellitus in the elderly. Specific sex-linked endocrine function is impaired or altered with age as well. Women typically experience menopause in their sixth decade of life, which is accompanied by an increased risk of cardiovascular disease, loss of bone mass, and atrophy of estrogen-responsive tissue.[12]
Function
The process of aging is well understood to be part of the natural progression of the human life cycle. Simply by virtue of cellular degradation combined with the loss of biosynthetic and cellular repair mechanisms that might have compensated for this degradation in our youth, aging is a chronic and unavoidable state that we will eventually all enter.
Mechanism
On a cellular level, aging is believed to result from a variety of factors related to cellular senescence. The overarching notion is that human cells can only replicate a finite number of times before they become senescent. Previous research in this field has shown that as a cell divides, telomeres on the DNA strand become gradually shortened.[13] The mechanism by which this occurs can be summarized by understanding that the telomeres appear to serve a chromosome-protective role. As the telomere length decreases, so too are the protective qualities of the proteins, which normally at the distal ends of the telomere and allow DNA repair enzymes to recognize telomeres amongst sites of DNA damage. As a result, the loss of telomere length and concomitant loss of these protective proteins exposes the ends of the chromosomes to damage by DNA repair enzymes.[14] This process is compounded by DNA repair complex-mediated activation of transcription factor p53, which, in conjunction with cyclin-dependent kinase inhibitor p21, can result in subsequent senescence of cells and, ultimately, cessation of their metabolic and replicative functions.[15]
Related Testing
Tests relevant to aging and its associated physiology are system and patient or pathology-specific. For example, in an elderly patient with confusion or alterations in neurological status, it might be valuable to administer the mini-mental state examination (MMSE) or, whereas in a patient of 20 years old with similar symptoms, the underlying pathology is likely, not due to dementia as it would be in the elderly patient, so different testing would be necessary.[16] Additionally, in patients with advanced age, certain routine screening tools or tests require implementation due to the unique set of health concerns experienced at older ages. For example, men should receive digital rectal exams for prostate cancer screening; women mammography for breast cancer screening, and annual colonoscopies are a great screening tool to exclude colon cancer in men and women alike. The purpose of such screening tools is to discover disease as early as possible in its clinical course and identify unhealthy lifestyles and behaviors for which the patient can then receive counseling.[17] Such tools are especially valuable in such an aging population as it is well understood that disease risk increases with age.
Pathophysiology
Three distinct processes can reasonably explain the pathophysiology underlying the aging process:
Production of Free Radicals
Free radicals are well known in the biochemical world as a normal byproduct of healthy physiology in well-regulated, relatively small amounts. They exist as a molecule with a single, unpaired valence electron, rendering them highly reactive in the presence of other substances as they attempt to interact with other substances in an effort to obtain additional valence electrons and balance the electron configuration.[18] The exact underlying mechanisms underlying the downstream adverse effects of free radical generation and subsequent interaction with cellular components is beyond the scope of this paper, but it bears mentioning that free radicals can denature proteins, destroy membrane lipids, nucleic acids, and certain organelles such as lysosomes and proteasomes.[19] The importance of understanding free radical or reactive oxygen species-derived degenerative changes is that the belief is that accumulated cellular damage via these molecules will—in time—cumulatively overwhelm the cell’s damage repair mechanisms, leading to the eventual physiologic collapse of first, the cell, then the whole organism.[18]
Glycation
Advanced glycosylation end-products form when reactions occur between aldehyde groups of reducing sugars and amino groups of proteins. The formation of these metabolic products occurs in a fashion dependent on elevated blood glucose.[20] In aging individuals, glycemic control becomes less regulated, and glucose tolerance can undergo significant alteration. The predominance of advanced glycosylation end-products can result in such abnormalities as vascular fibrosis, thickened basement membranes, impaired lipid metabolism, and reduced collagenous elasticity. Furthermore, advanced glycosylation end-products are associated with the induction of inflammatory responses, resulting in the release of inflammatory substances and reactive oxygen species, causing further tissue damage.[18]
Reduced Regenerative Capacity
In healthy individuals, a balance exists between one cell’s apoptosis and the maturation and healthy development of another cell that essentially takes the place of the first. Researchers believe that mechanisms within the cell cycle control both the programmed death of a senescent cell but also signal externally to other cells the need for the development of a new, healthy cell to backfill whatever metabolic demands the senescent cell might have been meeting. The progression between stages in the cell cycle is controlled by regulatory proteins, whose function demonstrably declines in senescent cells compared to younger, healthy cells. The ability of these protein-derived signaling pathways to communicate the need for cell regeneration and maturation in the healthy, young cells seems to be reduced in the aging process, while the pro-apoptotic pathway signaling mechanisms continue to function, leading to a net decline in functional, healthy cells.[18]
Clinical Significance
The aging process is a natural phenomenon that occurs due to a variety of loosely understood mechanisms. Via a combination of telomeric shortening, which triggers pro-apoptotic pathways when sensed in the cell cycle, which subsequently triggers inflammatory mediators and the release of damaging reactive oxygen species, our bodies and their ability to maintain physiologic homeostasis degrade with time. Moreover, so too does the body's ability to regenerate or reproduce healthy cells and tissues as we age. The aging process brings with it phenotypical changes that clinicians must understand and consider when caring for aging patients.
It is essential to recognize that aging involves a great deal of interplay between lifestyle and genetics. An individual who maintains a healthy lifestyle, has access to adequate, routine medical care and screenings, and enters into late adulthood with a clean bill of health will experience a vastly different aging process than someone who is sedentary, makes poor diet and lifestyle choices, and has lived with chronic disease before and upon entry into late adulthood.
Aging is relevant to clinical care and management because it often implies underlying derangements of normal physiology. As an example, this article mentioned earlier that urinary tract infections are more common in the elderly. Some patients may experience an increased frequency of falls due to the weakness imposed by their urinary tract infection or their bladder urgency forcing them to attempt to hurriedly make it to a toilet. Clinicians must remain vigilant of the manifestations of disease in aging, and likewise, the presentation of physiologic derangements that pose a potential risk to health, like falls and urinary tract infections.[21] Aging, although a normal aspect of typical physiology, does incur some manifestations of physiologic derangement that clinicians should learn to interpret in context.
Review Questions
References
- 1.
-
Pallin DJ, Espinola JA, Camargo CA. US population aging and demand for inpatient services. J Hosp Med. 2014 Mar;9(3):193-6. [PubMed]
- 2.
-
Partridge L, Deelen J, Slagboom PE. Facing up to the global challenges of ageing. Nature. 2018 Sep;561(7721):45-56. [PubMed]
- 3.
-
Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of Cellular Senescence. Trends Cell Biol. 2018 Jun;28(6):436-453. [PubMed]
- 4.
-
Tchkonia T, Kirkland JL. Aging, Cell Senescence, and Chronic Disease: Emerging Therapeutic Strategies. JAMA. 2018 Oct 02;320(13):1319-1320. [PubMed]
- 5.
-
Goldsmith TC. On the programmed/non-programmed aging controversy. Biochemistry (Mosc). 2012 Jul;77(7):729-32. [PubMed]
- 6.
-
Cosman D, Wignall J, Lewis A, Alpert A, Cerretti DP, Park L, Dower SK, Gillis S, Urdal DL. High level stable expression of human interleukin-2 receptors in mouse cells generates only low affinity interleukin-2 binding sites. Mol Immunol. 1986 Sep;23(9):935-41. [PubMed]
- 7.
-
Wyss-Coray T. Ageing, neurodegeneration and brain rejuvenation. Nature. 2016 Nov 10;539(7628):180-186. [PMC free article] [PubMed]
- 8.
-
Bhutto A, Morley JE. The clinical significance of gastrointestinal changes with aging. Curr Opin Clin Nutr Metab Care. 2008 Sep;11(5):651-60. [PubMed]
- 9.
-
Denic A, Glassock RJ, Rule AD. Structural and Functional Changes With the Aging Kidney. Adv Chronic Kidney Dis. 2016 Jan;23(1):19-28. [PMC free article] [PubMed]
- 10.
-
Strait JB, Lakatta EG. Aging-associated cardiovascular changes and their relationship to heart failure. Heart Fail Clin. 2012 Jan;8(1):143-64. [PMC free article] [PubMed]
- 11.
-
Janssens JP, Pache JC, Nicod LP. Physiological changes in respiratory function associated with ageing. Eur Respir J. 1999 Jan;13(1):197-205. [PubMed]
- 12.
-
Katorgina OA, Fil'ts MA. [Enzyme therapy in ophthalmology (review of the Soviet and foreign literature)]. Oftalmol Zh. 1972;27(3):215-22. [PubMed]
- 13.
-
de Magalhães JP, Passos JF. Stress, cell senescence and organismal ageing. Mech Ageing Dev. 2018 Mar;170:2-9. [PubMed]
- 14.
-
de Lange T. Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 2005 Sep 15;19(18):2100-10. [PubMed]
- 15.
-
Beauséjour CM, Krtolica A, Galimi F, Narita M, Lowe SW, Yaswen P, Campisi J. Reversal of human cellular senescence: roles of the p53 and p16 pathways. EMBO J. 2003 Aug 15;22(16):4212-22. [PMC free article] [PubMed]
- 16.
-
Larner AJ. Mini-Mental State Examination: diagnostic test accuracy study in primary care referrals. Neurodegener Dis Manag. 2018 Oct;8(5):301-305. [PubMed]
- 17.
-
Hackl F, Halla M, Hummer M, Pruckner GJ. The Effectiveness of Health Screening. Health Econ. 2015 Aug;24(8):913-35. [PubMed]
- 18.
-
Knapowski J, Wieczorowska-Tobis K, Witowski J. Pathophysiology of ageing. J Physiol Pharmacol. 2002 Jun;53(2):135-46. [PubMed]
- 19.
-
Reeg S, Grune T. Protein Oxidation in Aging: Does It Play a Role in Aging Progression? Antioxid Redox Signal. 2015 Jul 20;23(3):239-55. [PMC free article] [PubMed]
- 20.
- 21.