Pathophysiology of Cellular Aging

Pathophysiology of Cellular Aging

• Cellular aging, also known as senescence, is a complex process leading to progressive deterioration of cells and tissues.
• It's a multifaceted process involving alterations in cellular function, structure, and response to stress.
• This process contributes to age-related diseases and reduced physiological reserve.
• Various factors influence the cellular aging process, including genetic predisposition, environmental exposures, and lifestyle choices.
• Accumulation of cellular damage, such as DNA damage, oxidative stress, and protein damage, is central to the development of senescence.

Mechanisms of Cellular Aging

• Telomere shortening: Telomeres, protective caps at the ends of chromosomes, shorten with each cell division. This shortening eventually limits cellular replication, leading to cellular aging or senescence.
• Oxidative stress: Reactive oxygen species (ROS) are byproducts of cellular metabolism. Overproduction of ROS damages cellular components, including proteins, lipids, and DNA. Accumulation of this damage contributes significantly to cellular aging.
• Inflammation: Chronic low-grade inflammation, or inflammaging, is associated with aging. Inflammation can contribute to cellular damage and dysfunction.
• Epigenetic alterations: Epigenetic modifications, such as DNA methylation patterns, can change gene expression and affect cellular function as cells age.
• Mitochondrial dysfunction: Mitochondria are crucial for energy production in cells. Decline in mitochondrial function contributes to reduced energy availability. This functional limitation negatively impacts cellular processes, contributing to cellular aging.

Cellular Senescence

• Senescent cells are cells that have ceased dividing despite still being viable.
• These cells release a range of harmful molecules and signaling factors, often termed "senescence-associated secretory phenotype (SASP)".
• This SASP impacts the surrounding tissue contributing to a complex and dynamic range of effects on surrounding tissue including inflammation.
• The accumulation of senescent cells has been linked to age-related diseases including cardiovascular disease, neurodegenerative disorders, and cancer.

Impact of Cellular Aging

• Reduced cellular function: Cellular aging results in decreased efficiency in performing essential cellular tasks, such as DNA repair, protein synthesis, and energy production.
• Increased susceptibility to disease: Age-related diseases and conditions, like cancer, cardiovascular disease, and neurodegenerative diseases, are strongly linked to impaired cellular function associated with cellular aging.
• Compromised tissue homeostasis: Dysfunction of cellular mechanisms for repair, renewal, and maintenance impacts tissues, leading to a breakdown in tissue homeostasis.
• Altered immune function: The immune system's ability to recognize and respond to pathogens and foreign substances is affected, increasing susceptibility to infections and autoimmune diseases.
• Decline in physiological reserve: The body's ability to adapt to stress and maintain homeostasis decreases with age.
• Accumulation of cellular damage: Ongoing cellular damage, as indicated by indicators such as DNA damage and protein damage, accumulates over time, leading to malfunctions at the cellular level.

Cellular Senescence and Therapy

• The presence of senescent cells is recognized as an important contributor to age-related diseases.
• Research is focused on developing therapies to remove senescent cells or to modulate their activity.
• Senolytic drugs are a promising area of research targeting senescent cells and have shown some success in models to address age-related diseases and potentially improve human health.