Aging Hallmarks and Progression and Age-Related Diseases: A Landscape View of Research Advancement

Abstract

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.

Keywords: Aging; brain aging; epigenetic; inflammaging; longevity; senescence; stem cell; telomere.

Figure 1

Yearly growth of the number of aging-related documents (journal articles and patents) in the CAS Content Collection.

Figure 2

Scheme of the currently identified hallmarks of aging along with their classification.

Figure 3

(A) Scheme of the structures of chromosomes and telomeres. At their ends, chromosomes exhibit repeated base segments called telomeres, which truncate with each replication cycle. Telomeres are known to shorten upon cell division, as a result of incomplete replication. (B) Scheme of the common epigenetic alterations including DNA methylation and histone modifications. (C) Schematic presentation of normal cells and senescent cells, secreting a senescence-associated secretory phenotype (SASP). In the short term, senescence growth arrest prevents tumorigenesis and fibrosis. The loss of proliferative capacity, which accompanies senescence, impairs tissue regeneration and stimulates aging. SASP can promote tumor growth and progression by stimulating angiogenesis and extracellular matrix remodeling.

Figure 4

Interrelations between the hallmarks of aging.

Figure 5

Scheme of the Maillard reaction. Reducing sugar reactive carbonyl groups react with the proteins amino groups to form a Schiff base, which further rearranges to more stable Amadori products. These early glycation end products further form either protein adducts or protein cross-links.

Figure 6

Schematic presentation of the positive feedback loop between mitochondria dysfunction and oxidative stress upon aging.

Figure 7

Yearly growth of the number of documents related to brain aging in the CAS Content Collection.

Figure 8

Top countries (A), organizations (B), and scientific journals (C) publishing articles related to aging mechanisms and antiaging strategies.

Figure 9

Hallmarks of aging explored in the scientific publications: (A) number of publications exploring hallmarks of aging; (B) trends in number of publications exploring hallmarks of aging during the years 2018–2021.

Figure 10

Distribution of documents in the CAS Content Collection related to age-associated diseases.

Figure 11

Annual growth of number of documents related to age-associated diseases.

Figure 12

Correlation of the number of documents related to the hallmarks of aging with age-related diseases.

Figure 13

Relationship between the hallmarks of aging and the age-related diseases as revealed by the number of corelated documents (Figure 12).