JOURNAL OF GERONTOLOGY AND GERIATRICS

The aging muscle: sarcopenia, mitochondrial function, and redox biology

Aurelio Lo Buglio, Francesco Bellanti, Gianluigi Vendemiale — Mon, 25 Mar 2024 00:00:00 +0000

Sarcopenia, age-related skeletal muscle loss and weakened strength, hinders functional independence, elevates mortality risk, and strains healthcare systems. Diagnosis varies among working groups, leading to diverse prevalence estimates. Recent meta-analyses suggest a 10% overall prevalence, increasing with age and peaking at 50% for those aged 80 or older. Standardized diagnostic criteria are essential for addressing this significant health concern. Sarcopenia is associated with structural and functional muscle changes, including mitochondrial alterations and disruptions in redox balance. Given the pivotal role of mitochondria in the pathogenesis of sarcopenia, further preclinical and clinical studies are needed to gain a deeper comprehension of redox signaling pathways and to identify targeted therapeutic strategies.

Healthy aging: when periodontal health matters

Wed, 05 Apr 2023 00:00:00 +0000

Providing care for the elderly has been considered a significant challenge for modern medicine. As age progresses, diseases become more frequent and severe than those observed at a younger age. This is particularly relevant for infectious diseases, typical in the elderly and usually associated with poor outcomes. Moreover, when persisting and diffusing into the bloodstream (i.e. bacteremia), these infections keep up with the demand for immune cells’ response and consequently increase the concentration of inflammatory markers systemically. This phenomenon is known as “inflammaging”, which potentially triggers or facilitates the development and progression of several age-related disorders, such as cancer, cardiovascular and neurodegenerative diseases. Periodontal disease is one of the most prominent among the disparate number of causal factors responsible for bacteremia and low-grade systemic inflammation in the aging population. This inflammatory disorder is triggered by a dysbiosis of certain bacterial species that activates a massive local toxic deleterious immune response leading to non-reversible damage of supportive tissues surrounding the teeth. In chronic, oral pathogens and their toxic factors can penetrate the bloodstream contributing to systemic inflammation. Based on this premise, it seems evident that maintaining oral health in the elderly is vital not just for owning healthy mouth but also because it contributes to a healthy aging. This review provides an updated account of molecular insights into the bidirectional association between oral health and “successful” aging.

The heterogeneous approach to reach longevity: the experience of Italian centenarians

Beatrice Arosio, Evelyn Ferri, Daniela Mari, Giovanni Vitale — Mon, 25 Mar 2024 00:00:00 +0000

People reaching old age are increasing exponentially in recent decades, and centenarians represent the fastest-growing group. Aging is characterized by the continuous adaptation of the organism to life-long exposure to stress that leads to a relevant clinical complexity. It is reasonable to think that centenarians do not escape the physiological decline or the age-related diseases and syndromes, but the rate of such processes is slow enough to be counterbalanced by their increased capacity to respond to stresses. Therefore, depending on the ability of each person to respond successfully or unsuccessfully to stressors, the aging process changes, leading to extremely heterogeneous phenotypes, particularly evident among centenarians. In a cohort of Italian centenarians, the high heterogeneity in health status was well captured by means of the Frailty Index (FI) computed utilizing clinical variables. Surprisingly, in the same cohort, a FI computed utilizing biological variables showed average lower values and a narrower distribution than the clinical one. Interestingly, these centenarians showed higher blood free T4 (FT4) and thyroid-stimulating hormone (TSH) levels, and lower blood free T3 (FT3) levels and FT3/ FT4 ratio than younger persons. Moreover, their endocrine profile was characterized by high adiponectin levels and insulin sensitivity, and low insulin growth factor-1 (IGF-1) and leptin levels. Under these premises, studies on centenarians open a window to extreme longevity. Metabolic remodelling of these persons is suggestive of benefits that play a critical and positive role in shaping healthy aging.

Changes in cholesterol homeostasis associated with aging and with age-related conditions: pathophysiological and clinical implications

Marco Bertolotti, Giulia Lancellotti, Chiara Mussi — Mon, 25 Mar 2024 09:57:29 +0000

The increase in life expectancy is leading to a progressive rise in the percentage of older people in the general population, and consequently in the prevalence of chronic diseases, often leading to disability. Age-related modifications in cholesterol homeostasis, the increase in plasma cholesterol levels due to aging, represents a cardio- and cerebrovascular risk factor in adjunct to age itself. Direct knowledge about the pathophysiological alterations of cholesterol metabolism is limited. Clinical-experimental evidence about cholesterol lowering treatment suggests that the benefits observed in the general population are also observed in older age groups. However, patients enrolled in clinical trials often do not represent real-life clinical scenarios, limiting the generalizability of research findings. Issues of complexity and frailty are mostly inadequately addressed in published studies and guidelines. Further, effects of cholesterol itself and cholesterol lowering on cognitive function are still controversial. This narrative review focuses on current evidence about the pathophysiology and clinical implications of the relationship between cholesterol and aging. Some suggestions will be provided, underlining the need for careful, personalized evaluation of the patient’s functional status, along with clinical competence and geriatric skills.

Common neurodegenerative pathways in brain aging, cognitive decline, type 2 diabetes & metabolic syndrome

Mon, 25 Mar 2024 00:00:00 +0000

Aging and age-related diseases share several biological mechanisms, forming a finely controlled network where inflammation plays an encompassing key role. In the Central Nervous System (CNS), glial cells can modulate neuroinflammation by promoting neuronal homeostasis and limit neurodegeneration. However, age-related systemic inflammation (i.e. inflammaging) leads to additional deteriorations of both microglia and astrocytes causing an exacerbation response of these cells to stimuli. Type 2 diabetes (T2DM), a chronic metabolic disorder characterized by hyperglycemia, has also been associated with multiple organs loss, including the brain. Numerous studies have underlined direct correlations between diabetes, cognitive decline and dementia, however exact mechanisms related to neurodegeneration in T2DM remain to be elucidated. It widely recognized that aging is considered the most critical risk factor for Alzheimer’s disease (AD), however there are increasing data highlighting that metabolic disorders are also strongly associated with an increased risk of AD and T2DM. Indeed, impaired glucose metabolism and mitochondrial activity are common grounds for cognitive dysfunction and AD. The Metabolic syndrome (MetS) in mid-life may accelerate the progression of AD pathogenesis by activating an increased productions neuroinflammatory biomarkers leading to amyloid pathology degeneration. There remains an intricate crosstalk between the aging process, T2DM, MetS, and neuroinflammation, thus resulting in neuronal loss and the development of cognitive impairment with an accelerated risk of AD. Future studies are needed to identify potential therapeutic benefits related to improving neuroinflammation on cognitive performance.