Politically important article in Science Translational Medicine

The authors are: Michael J. Rae, Robert N. Butler, Judith Campisi, Aubrey D. N. J. de Grey, Caleb E. Finch, Michael Gough, George M. Martin, Jan Vijg, Kevin M. Perrott, Barbara J. Logan.

The article was published on July, 14. The authors advocate that funding of scientific research is substantailly increased and interventions for aging humans are developed.

Progressive accumulation of aging damage is the physiological cause of numerous age-related pathologies, loss of functionality and increased mortality. Aging places an unprecedented economic and social challenges, as the global increase of medical costs and decreased national workforce's ability. Interventions to to retard, arrest, and even reverse aging damage need to be developed in order to prevent our society from experiencing these catastrophes. 

I'd like to pay more attention to the particular research directions. To my mind the authors focused on some really important areas. I put them here in a form of a list, I guess it's better if one adds numbers.

1. Loss of Proliferative Homeostasis: embraces

1.1. age-related hyperplasia (including excessive proliferation of osteoclasts, interstitial fibrosis, and, above all, cancer),

1.2. loss of tissue renewal through stem cell attrition (due, e.g., to cellular senescence, apoptosis)
or atrophy (from systemic endocrinological and signaling changes)

1.3. as well as aberrant differentiation (e.g., accumulation of mesenchymal adipocyte-like cells in aged
tissues, incomplete myocyte development in skeletal muscle, osteoblast-like
differentiation of calcifying vascular smooth muscle cells, adipogenic transformation of
thymic stromal cells in thymic involution, etc)

2. Neurodegeneration: including but not limited to

2.1. age-related neurological diseases such as Parkinson’s and Alzheimer’s diseases,

2.2. aging changes not normally classified as specific diseases:

2.2.1. neuronal loss

2.2.2. synaptic atrophy

2.2.3. loss of synaptic plasticity

2.2.4. loss of interneuronal and intracerebral connectivity

2.2.5. dendritic spine pathology

2.2.6. simplification of neuronal cell geometry

2.2.7. age-related peripheral and autonomic neuropathy

2.2.8. (arguably) tcerebrovascular lipohyalinosis

3. Somatic Mutations: occur with aging in both nuclear and mitochondrial DNA.

3.1. somatic nuclear mutations are essential to age-related cancers and possibly other age-related
dysfunction

3.2. mitochondrial mutations (especially deletions) accumulate with aging in postmitotic cells, and appear to contribute to age-related disease (Parkinson’s disease, sarcopenia, possibly type II diabetes and congestive heart failure) and rising oxidative stress

3.3. other mitochondrial structural and functional alterations also appear to occur, although cause and effect, adaption vs. dysfunction, functional importance, and other uncertainties remain

4. Nonadaptive Changes in Gene Expression:

4.1. increasing variability in gene expression with aging that does not support homeostasis in a changed local or systemic milieu

4.2. includes epimutations and epigenetic drift, which may be initially adaptive, by
allowing for metabolic flexibility or adaptability, but become progressively deleterious

5. Immunosenescence:

5.1. age-related reductions in adaptive (and possibly humoral) immunity

5.2. alterations in innate immunity associated with thymic involution and alterations in T-cells 

5.3. heretofore little-understood increases in autoantibodies and alterations in innate immunity. Immunosenescence underlies the dramatic increase in morbidity and mortality from infectious disease with age

6. Nonadaptive Inflammation:

6.1. elevations in inflammatory cytokines (notably interleukin-6) and acute-phase reactants (especially C-reactive protein) occur, associated with several age-related diseases, increased frailty, and mortality

6.2. While anti-inflammatory therapies may prove useful, research should center on developing therapies for the primary cause(s), such as:

6.2.1. impaired cell-mediated immunity

6.2.2. persistent pathogen infection

6.2.3. oxidative stress

6.2.4. imperfectly-healed injuries

6.2.5.accumulation of senescent cells and adipose tissue macrophages (ATMs)

6.2.6. age-related autoimmunity

6.2.7. possibly impaired target-cell response

7. Alterations of the Extracellular Milieu: include

7.1. thickening of basement membranes

7.2. degradation of tight junctions

7.3. accumulation of amyloids

7.4. crosslinking of long-lived structural proteins by advanced glycation endproducts (AGE)

7.5. proteoglycan alterations

7.6. degradation of tissue elastin structure

7.7. mechanical/structural breakdown 

7.8. may include chronic shifts in signaling milieu, although these are expected to be
secondary to primary age changes and revert upon remediation

Comments

[She_Liger]

Не такая уж и важная...
Обычный "винегрет" информации при полном отсутствии понимания.
Впрочем, это - стандартная ситуация, наблюдающаяся незадолго до очередного научного открытия...

[Андрей]

Согласен с комментарием по поводу винегрета. Все это напоминает классификацию (систематику) видов живых огранизмов до Дарвина или даже до Линнея или скажем систему (или отсутствие таковой) в описании химических элементов до Менделеева.

[Maria Konovalenko]

Have you both not read the abstract of the article?
This is not a systematization of any kind. This is a list of main research areas that need to be the focus of investigations and development of late-onset therapies.