Mitochondrial function in ageing: coordination with signalling and transcriptional pathways
Fei Yin1, Harsh Sancheti1, Zhigang Liu1
1Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089-9121, USA.
The Journal of Physiology
|August 22, 2015
Summary
Mitochondrial dysfunction is a key factor in aging and related diseases, affecting brain, liver, and heart. Targeting mitochondrial communication pathways offers novel therapeutic strategies for age-related disorders.
Area of Science:
- Biochemistry
- Cell Biology
- Neuroscience
Background:
- Mitochondrial dysfunction, marked by reduced energy production and altered redox balance, is an early event in aging.
- This dysfunction is prominent in high-metabolic tissues like the brain, liver, and heart, contributing to age-related diseases.
- In aging brains and Alzheimer's disease, mitochondrion-centered hypometabolism is evident, characterized by decreased neuronal glucose uptake and altered astrocyte metabolism.
Purpose of the Study:
- To investigate the role of mitochondrial dysfunction in aging and age-related disorders.
- To explore the cellular mechanisms underlying mitochondrial communication with other cellular components.
- To identify potential therapeutic targets for mitochondrion-implicated age-related diseases.
Main Methods:
- Review of recent findings on mitochondrial function in aging CNS, liver, and adipose tissues.
- Analysis of cellular signaling pathways involving mitochondria, including kinase signaling and transcriptional pathways.
- Examination of metabolic shifts and alterations in mitochondrial function.
Main Results:
- Mitochondrial dysfunction contributes to hypometabolism in aging brains and is linked to Alzheimer's disease.
- Declining mitochondrial capacity in liver and adipose tissue is associated with age-related metabolic disorders like obesity and type 2 diabetes.
- Mitochondria function as part of a dynamic cellular network, interacting with other components via signaling pathways.
Conclusions:
- Mitochondrial dysfunction is a critical factor in aging and associated diseases across multiple tissues.
- Understanding the molecular mechanisms of mitochondria-cell communication is crucial for developing new therapies.
- Targeting mitochondrial function and signaling cascades presents a promising therapeutic avenue for age-related disorders.
Related Concept Videos
01:37Mitochondria
21.4K
Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
21.4K
01:46Electron Transport Chain: Complex I and II
19.6K
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
19.6K
01:26Aging
1.0K
Aging is a complex biological phenomenon influenced by various processes that affect cellular and systemic functions. Several prominent theories attempt to explain its mechanisms, highlighting cellular limitations, oxidative damage, and hormonal changes as central factors in aging.
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...
1.0K
03:03mTOR Signaling and Cancer Progression
5.1K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
5.1K
01:45Mitochondrial Membranes
17.9K
A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
17.9K
01:19The Effect of Aging on Tissues
4.1K
Several body functions deteriorate with age. The external signs of aging are easily identifiable. For example, the skin becomes dry, less elastic, and thins out, forming wrinkles. The skin of the face begins to appear looser due to a decrease in the levels of elastic and collagen fibers in the connective tissue. Additionally, melanin production in the hair follicle decreases with age, resulting in gray hair. Moreover, the senses of sight and hearing decline, so glasses and hearing aids may...
4.1K